@article{blanco-meloIntrinsicCellularDefenses2012, title = {Intrinsic {{Cellular Defenses}} against {{Human Immunodeficiency Viruses}}}, author = {{Blanco-Melo}, Daniel and Venkatesh, Siddarth and Bieniasz, Paul~D.}, year = 2012, month = sep, journal = {Immunity}, volume = {37}, number = {3}, pages = {399--411}, issn = {10747613}, doi = {10.1016/j.immuni.2012.08.013}, urldate = {2026-08-18}, copyright = {https://www.elsevier.com/tdm/userlicense/1.0/}, langid = {english}, pmcid = {PMC3912573}, pmid = {22999946}, file = {C:\Users\adama\Zotero\storage\V2BCWVEK\Blanco-Melo et al. - 2012 - Intrinsic Cellular Defenses against Human Immunodeficiency Viruses.pdf} } @article{choiSAMHD1SpecificallyRestricts2015, title = {{{SAMHD1}} Specifically Restricts Retroviruses through Its {{RNase}} Activity}, author = {Choi, Jongsu and Ryoo, Jeongmin and Oh, Changhoon and Hwang, Sungyeon and Ahn, Kwangseog}, year = 2015, month = dec, journal = {Retrovirology}, volume = {12}, number = {1}, pages = {46}, issn = {1742-4690}, doi = {10.1186/s12977-015-0174-4}, urldate = {2026-08-18}, langid = {english}, pmcid = {PMC4450836}, pmid = {26032178}, file = {C:\Users\adama\Zotero\storage\JALLHWGA\Choi et al. - 2015 - SAMHD1 specifically restricts retroviruses through its RNase activity.pdf} } @article{cogginsSAMHD1FunctionsHuman2020, title = {{{SAMHD1 Functions}} and {{Human Diseases}}}, author = {Coggins, Si'Ana A. and Mahboubi, Bijan and Schinazi, Raymond F. and Kim, Baek}, year = 2020, month = mar, journal = {Viruses}, volume = {12}, number = {4}, pages = {382}, issn = {1999-4915}, doi = {10.3390/v12040382}, urldate = {2026-08-18}, abstract = {Deoxynucleoside triphosphate (dNTP) molecules are essential for the replication and maintenance of genomic information in both cells and a variety of viral pathogens. While the process of dNTP biosynthesis by cellular enzymes, such as ribonucleotide reductase (RNR) and thymidine kinase (TK), has been extensively investigated, a negative regulatory mechanism of dNTP pools was recently found to involve sterile alpha motif (SAM) domain and histidine-aspartate (HD) domain-containing protein 1, SAMHD1. When active, dNTP triphosphohydrolase activity of SAMHD1 degrades dNTPs into their 2{$\prime$}-deoxynucleoside (dN) and triphosphate subparts, steadily depleting intercellular dNTP pools. The differential expression levels and activation states of SAMHD1 in various cell types contributes to unique dNTP pools that either aid (i.e., dividing T cells) or restrict (i.e., nondividing macrophages) viral replication that consumes cellular dNTPs. Genetic mutations in SAMHD1 induce a rare inflammatory encephalopathy called Aicardi--Gouti\`eres syndrome (AGS), which phenotypically resembles viral infection. Recent publications have identified diverse roles for SAMHD1 in double-stranded break repair, genome stability, and the replication stress response through interferon signaling. Finally, a series of SAMHD1 mutations were also reported in various cancer cell types while why SAMHD1 is mutated in these cancer cells remains to investigated. Here, we reviewed a series of studies that have begun illuminating the highly diverse roles of SAMHD1 in virology, immunology, and cancer biology.}, langid = {english}, pmcid = {PMC7232136}, pmid = {32244340} } @article{felipModulationDNADamage2022, title = {Modulation of {{DNA Damage Response}} by {{SAM}} and {{HD Domain Containing Deoxynucleoside Triphosphate Triphosphohydrolase}} ({{SAMHD1}}) {{Determines Prognosis}} and {{Treatment Efficacy}} in {{Different Solid Tumor Types}}}, author = {Felip, Eudald and {Guti{\'e}rrez-Chamorro}, Luc{\'i}a and G{\'o}mez, Maica and {Garcia-Vidal}, Edurne and Romeo, Margarita and Mor{\'a}n, Teresa and Layos, Laura and {P{\'e}rez-Roca}, Laia and {Riveira-Mu{\~n}oz}, Eva and Clotet, Bonaventura and Fernandez, Pedro Luis and Mes{\'i}a, Ricard and {Mart{\'i}nez-Card{\'u}s}, Anna and Ballana, Ester and Margel{\'i}, Mireia}, year = 2022, month = jan, journal = {Cancers}, volume = {14}, number = {3}, pages = {641}, issn = {2072-6694}, doi = {10.3390/cancers14030641}, urldate = {2026-08-18}, abstract = {SAMHD1 is a deoxynucleotide triphosphate (dNTP) triphosphohydrolase with important roles in the control of cell proliferation and apoptosis, either through the regulation of intracellular dNTPs levels or the modulation of the DNA damage response. However, SAMHD1{$\prime$}s role in cancer evolution is still unknown. We performed the first in-depth study of SAMHD1{$\prime$}s role in advanced solid tumors, by analyzing samples of 128 patients treated with chemotherapy agents based on platinum derivatives and/or antimetabolites, developing novel in vitro knock-out models to explore the mechanisms driving SAMHD1 function in cancer. Low (or no) expression of SAMHD1 was associated with a positive prognosis in breast, ovarian, and non-small cell lung cancer (NSCLC) cancer patients. A predictive value was associated with low-SAMHD1 expression in NSCLC and ovarian patients treated with antimetabolites in combination with platinum derivatives. In vitro, SAMHD1 knock-out cells showed increased {$\gamma$}-H2AX and apoptosis, suggesting that SAMHD1 depletion induces DNA damage leading to cell death. In vitro treatment with platinum-derived drugs significantly enhanced {$\gamma$}-H2AX and apoptotic markers expression in knock-out cells, indicating a synergic effect of SAMHD1 depletion and platinum-based treatment. SAMHD1 expression represents a new strong prognostic and predictive biomarker in solid tumors and, thus, modulation of the SAMHD1 function may constitute a promising target for the improvement of cancer therapy.}, langid = {english}, pmcid = {PMC8833711}, pmid = {35158911} } @article{goldstoneHIV1RestrictionFactor2011, title = {{{HIV-1}} Restriction Factor {{SAMHD1}} Is a Deoxynucleoside Triphosphate Triphosphohydrolase}, author = {Goldstone, David C. and {Ennis-Adeniran}, Valerie and Hedden, Joseph J. and Groom, Harriet C. T. and Rice, Gillian I. and Christodoulou, Evangelos and Walker, Philip A. and Kelly, Geoff and Haire, Lesley F. and Yap, Melvyn W. and De Carvalho, Luiz Pedro S. and Stoye, Jonathan P. and Crow, Yanick J. and Taylor, Ian A. and Webb, Michelle}, year = 2011, month = dec, journal = {Nature}, volume = {480}, number = {7377}, pages = {379--382}, issn = {0028-0836, 1476-4687}, doi = {10.1038/nature10623}, urldate = {2026-08-18}, copyright = {http://www.springer.com/tdm}, langid = {english}, pmid = {22056990} } @article{gottigApobec3ADeaminationFunctions2023, title = {{{Apobec3A Deamination Functions Are Involved}} in {{Antagonizing Efficient Human Adenovirus Replication}} and {{Gene Expression}}}, author = {G{\"o}ttig, Lilian and Wei{\ss}, Christina and Stubbe, Miona and Hanrieder, Lisa and Hofmann, Samuel and Grodziecki, Alessandro and Stadler, Daniela and Carpentier, Arnaud and Protzer, Ulrike and Schreiner, Sabrina}, editor = {Harris, Reuben S. and Goff, Stephen P.}, year = 2023, month = jun, journal = {mBio}, volume = {14}, number = {3}, pages = {e03478-22}, issn = {2150-7511}, doi = {10.1128/mbio.03478-22}, urldate = {2026-08-18}, abstract = {Our data provide a novel conceptual insight into the virus/host-cell interplay, changing the current view of how a host-cell can defeat a virus infection. Thus, our study reveals a novel and general impact of cellular Apobec3A on the intervention of human adenovirus (HAdV) gene expression and replication by improving the host antiviral defense mechanisms, thereby providing a novel basis for innovative antiviral strategies in future therapeutic settings. , ABSTRACT Apobec3A is involved in the antiviral host defense, targeting nuclear DNA, introducing point mutations, and thereby activating DNA damage response (DDR). Here, we found a significant upregulation of Apobec3A during HAdV infection, including Apobec3A protein stabilization mediated by the viral proteins E1B-55K and E4orf6, which subsequently limited HAdV replication and most likely involved a deaminase-dependent mechanism. The transient silencing of Apobec3A enhanced adenoviral replication. HAdV triggered Apobec3A dimer formation and enhanced activity to repress the virus. Apobec3A decreased E2A SUMOylation and interfered with viral replication centers. A comparative sequence analysis revealed that HAdV types A, C, and F may have evolved a strategy to escape Apobec3A-mediated deamination via reduced frequencies of TC dinucleotides within the viral genome. Although viral components induce major changes within infected cells to support lytic life cycles, our findings demonstrate that host Apobec3A-mediated restriction limits virus replication, albeit that HAdV may have evolved to escape this restriction. This allows for novel insights into the HAdV/host-cell interplay, which broaden the current view of how a host cell can limit HAdV infection. IMPORTANCE Our data provide a novel conceptual insight into the virus/host-cell interplay, changing the current view of how a host-cell can defeat a virus infection. Thus, our study reveals a novel and general impact of cellular Apobec3A on the intervention of human adenovirus (HAdV) gene expression and replication by improving the host antiviral defense mechanisms, thereby providing a novel basis for innovative antiviral strategies in future therapeutic settings. Ongoing investigations of the cellular pathways that are modulated by HAdV are of great interest, particularly since adenovirus-based vectors actually serve as COVID vaccine vectors and also frequently serve as tools in human gene therapy and oncolytic treatment options. HAdV constitute an ideal model system by which to analyze the transforming capabilities of DNA tumor viruses as well as the underlying molecular principles of virus-induced and cellular tumorigenesis.}, langid = {english}, pmcid = {PMC10294656}, pmid = {37154747}, file = {C:\Users\adama\Zotero\storage\6PQNJ324\Göttig et al. - 2023 - Apobec3A Deamination Functions Are Involved in Antagonizing Efficient Human Adenovirus Replication a.pdf} } @article{gutierrez-chamorroSAMHD1ExpressionModulates2023, title = {{{SAMHD1}} Expression Modulates Innate Immune Activation and Correlates with Ovarian Cancer Prognosis}, author = {{Guti{\'e}rrez-Chamorro}, Luc{\'i}a and Felip, Eudald and {Bernat-Peguera}, Adri{\`a} and Ezeonwumelu, Ifeanyi Jude and Teruel, Iris and {Mart{\'i}nez-Card{\'u}s}, Anna and Clotet, Bonaventura and {Riveira-Mu{\~n}oz}, Eva and Romeo, Margarita and Margel{\'i}, Mireia and Ballana, Ester}, year = 2023, month = feb, journal = {Frontiers in Immunology}, volume = {14}, pages = {1112761}, issn = {1664-3224}, doi = {10.3389/fimmu.2023.1112761}, urldate = {2026-08-18}, abstract = {Purpose SAMHD1 is a deoxynucleotide triphosphate (dNTP) triphosphohydrolase which has been proposed as a putative prognostic factor in haematological cancers and certain solid tumours, although with controversial data. Here, we evaluate SAMHD1 function in ovarian cancer, both in vitro and in ovarian cancer patients. Methods SAMHD1 expression was downregulated in ovarian cancer cell lines OVCAR3 and SKOV3 by RNA interference. Gene and protein expression changes in immune signalling pathways were assessed. SAMHD1 expression in ovarian cancer patients was evaluated by immunohistochemistry and survival analysis was performed according to SAMHD1 expression. Results SAMHD1 knockdown induced a significant upregulation of proinflammatory cytokines concomitant to increased expression of the main RNA-sensors, MDA5 and RIG-I, and interferon-stimulated genes, supporting the idea that the absence of SAMHD1 promotes innate immune activation in vitro . To assess the contribution of SAMHD1 in ovarian cancer patients, tumours were stratified in SAMHD1-low and SAMHD1-high expressing tumours, resulting in significantly shorter progression free survival (PFS) and overall survival (OS) in SAMHD1-high expression subgroup ( p =0.01 and 0.04, respectively). Conclusions SAMHD1 depletion correlates with increased innate immune cell signalling in ovarian cancer cells. In clinical samples, SAMHD1-low expressing tumors showed increased progression free survival and overall survival irrespective of BRCA mutation status. These results point towards SAMHD1 modulation as a new therapeutic strategy, able to enhance innate immune activation directly in tumour cells, leading to improved prognosis in ovarian cancer.}, pmcid = {PMC9948397}, pmid = {36845138}, file = {C:\Users\adama\Zotero\storage\3GISXLXM\Gutiérrez-Chamorro et al. - 2023 - SAMHD1 expression modulates innate immune activation and correlates with ovarian cancer prognosis.pdf} } @article{hayesExpressionMxAEsophageal2024, title = {Expression of {{{\textsc{MxA}}}} in Esophageal Cancer Cell Lines Can Influence Sensitivity to Chemotherapeutic Agents but This Does Not Require Apoptosis}, shorttitle = {Expression Of}, author = {Hayes, R. M. and O'Donovan, T. R. and McKenna, S. L.}, year = 2024, month = sep, journal = {Cancer Medicine}, volume = {13}, number = {17}, pages = {e70173}, issn = {2045-7634, 2045-7634}, doi = {10.1002/cam4.70173}, urldate = {2026-08-18}, abstract = {Abstract Esophageal cancer is a poor prognosis cancer characterized by intrinsic or acquired resistance to chemotherapeutic agents. The primary determinants of treatment failure are unknown. Expression of an anti-viral protein, myxovirus resistance protein A (MxA) is de-regulated in many cancers, including esophageal cancer, and its activity has been linked to apoptosis. This study has assessed whether MxA expression can influence the response of esophageal cancer cells to the chemotherapeutic agents 5-fluorouracil (5-FU) or oxaliplatin. MxA protein was differentially expressed in a panel of five esophageal cancer cell lines. KYSE450 and KYSE140 cells did not express MxA and were apoptosis incompetent. FLO-1, KYSE270, and OE21 cells expressed MxA, were more drug-sensitive and were apoptosis competent. MxA was artificially overexpressed in cell lines with no endogenous expression (KYSE450 and KYSE140). This increased the resistance of KYSE450 but not KYSE140 cells. Both cell lines remained apoptosis incompetent. We then evaluated siRNA knockdown of MxA in FLO-1 cells and CRISPR knockout in OE21 cells. Knockdown of MxA significantly increased drug sensitivity and caspase-3 activation in FLO-1 cells. OE21- MX1 KO cells were also more drug-sensitive, but in contrast to FLO-1 cells, caspase-3 activation was reduced. Collectively these data indicate that MxA can promote resistance to chemotherapy, but this does not always correspond with effects on apoptosis. Effects on apoptosis are cell line specific, suggesting that other co-operating pathways determine the overall impact of MxA. Importantly, in cancer cells that overexpress the protein, drug sensitivity can be improved by interfering with MxA.}, langid = {english}, pmcid = {PMC11405456}, pmid = {39285636}, file = {C:\Users\adama\Zotero\storage\22EYBVI3\Hayes et al. - 2024 - Expression of MxA in esophageal cancer cell lines can.pdf} } @article{heBST2InducedMacrophage2023, title = {{{BST2}} Induced Macrophage {{M2}} Polarization to Promote the Progression of Colorectal Cancer}, author = {He, Xuefeng and Chen, Huaijun and Zhong, Xinyang and Wang, Yaxian and Hu, Zijuan and Huang, Huixia and Zhao, Senlin and Wei, Ping and Shi, Debing and Li, Dawei}, year = 2023, journal = {International Journal of Biological Sciences}, volume = {19}, number = {1}, pages = {331--345}, issn = {1449-2288}, doi = {10.7150/ijbs.72538}, urldate = {2026-08-18}, langid = {english}, pmcid = {PMC9760448}, pmid = {36594082}, file = {C:\Users\adama\Zotero\storage\I9DGNTKU\He et al. - 2023 - BST2 induced macrophage M2 polarization to promote the progression of colorectal cancer.pdf} } @article{howardNuclearDNASensor2022, title = {The {{Nuclear DNA Sensor IFI16 Indiscriminately Binds}} to and {{Diminishes Accessibility}} of the {{HSV-1 Genome}} to {{Suppress Infection}}}, author = {Howard, Timothy R. and Lum, Krystal K. and Kennedy, Michelle A. and Cristea, Ileana M.}, editor = {{Nita-Lazar}, Aleksandra}, year = 2022, month = jun, journal = {mSystems}, volume = {7}, number = {3}, pages = {e00198-22}, issn = {2379-5077}, doi = {10.1128/msystems.00198-22}, urldate = {2026-08-18}, abstract = {Mammalian host defense against viral infection includes broad-acting cellular restriction factors, as well as effectors of intrinsic and innate immunity. IFI16 is a critical nuclear host defense factor and intrinsic immune protein involved in binding viral DNA genomes, thereby repressing the replication of nucleus-replicating viruses, including the human herpes simplex virus 1. , ABSTRACT Human cells identify invading pathogens and activate immune signaling pathways through a wide array of pattern recognition receptors, including DNA sensors. The interferon-inducible protein 16 (IFI16) is a nuclear DNA sensor that recognizes double-stranded DNA from a number of viral sources, including genomes of nuclear-replicating viruses. Among these is the prevalent human pathogen herpes simplex virus 1 (HSV-1). Upon binding to the HSV-1 DNA genome, IFI16 both induces antiviral cytokine expression and suppresses virus gene expression. Here, we used a multiomics approach of DNA sequencing techniques paired with targeted mass spectrometry to obtain an extensive view of the interaction between IFI16 and the HSV-1 genome and how this binding affects the viral DNA structure and protein expression. Through chromatin immunoaffinity purification coupled with next-generation DNA sequencing (ChIP-seq), we found that IFI16 binds to the HSV-1 genome in a sequence-independent manner while simultaneously exhibiting broad enrichment at two loci: UL30, the viral DNA polymerase gene, and US1 to US7. The assay for transposase-accessible chromatin with sequencing (ATAC-seq) revealed that these two regions are among the most accessible stretches of DNA on the genome, thereby facilitating IFI16 binding. Accessibility of the entire HSV-1 genome is elevated upon IFI16 knockout, indicating that expression of IFI16 globally induces chromatinization of viral DNA. Deletion of IFI16 also results in a global increase in the expression of HSV-1 proteins, as measured by parallel reaction monitoring-mass spectrometry of viral proteins representing 80\% of the HSV-1 genome. Altogether, we demonstrate that IFI16 interacts with the HSV-1 genome in a sequence-independent manner, coordinating epigenetic silencing of the viral genome and decreasing protein expression and virus replication. IMPORTANCE Mammalian host defense against viral infection includes broad-acting cellular restriction factors, as well as effectors of intrinsic and innate immunity. IFI16 is a critical nuclear host defense factor and intrinsic immune protein involved in binding viral DNA genomes, thereby repressing the replication of nucleus-replicating viruses, including the human herpes simplex virus 1. What has remained unclear is where on the viral genome IFI16 binds and how binding affects both viral DNA structural accessibility and viral protein expression. Our study provides a global view of where and how a nuclear restriction factor of DNA viruses associates with viral genomes to exert antiviral functions during early stages of an acute virus infection. Our study can additionally serve as a systems-level model to evaluate nuclear DNA sensor interactions with viral genomes, as well as the antiviral outcomes of transcriptionally silencing pathogen-derived DNA.}, langid = {english}, pmcid = {PMC9239196}, pmid = {35575489}, file = {C:\Users\adama\Zotero\storage\WS6GGNHG\Howard et al. - 2022 - The Nuclear DNA Sensor IFI16 Indiscriminately Binds to and Diminishes Accessibility of the HSV-1 Gen.pdf} } @article{hurInnateImmunityProtein2020, title = {The Innate Immunity Protein {{IFITM3}} Modulates {$\gamma$}-Secretase in {{Alzheimer}}'s Disease}, author = {Hur, Ji-Yeun and Frost, Georgia R. and Wu, Xianzhong and Crump, Christina and Pan, Si Jia and Wong, Eitan and Barros, Marilia and Li, Thomas and Nie, Pengju and Zhai, Yujia and Wang, Jen Chyong and Tcw, Julia and Guo, Lei and McKenzie, Andrew and Ming, Chen and Zhou, Xianxiao and Wang, Minghui and Sagi, Yotam and Renton, Alan E. and Esposito, Bianca T. and Kim, Yong and Sadleir, Katherine R. and Trinh, Ivy and Rissman, Robert A. and Vassar, Robert and Zhang, Bin and Johnson, Douglas S. and Masliah, Eliezer and Greengard, Paul and Goate, Alison and Li, Yue-Ming}, year = 2020, month = oct, journal = {Nature}, volume = {586}, number = {7831}, pages = {735--740}, issn = {0028-0836, 1476-4687}, doi = {10.1038/s41586-020-2681-2}, urldate = {2026-08-18}, langid = {english}, pmcid = {PMC7919141}, pmid = {32879487} } @article{jinBST2PromotesGrowth2019, title = {{{BST2}} Promotes Growth and Induces Gefitinib Resistance in Oral Squamous Cell Carcinoma via Regulating the {{EGFR}} Pathway}, author = {Jin, Huang and Zhang, Lianping and Wang, Shufang and Qian, Lei}, year = 2019, month = jul, journal = {Archives of Medical Science}, issn = {1734-1922, 1896-9151}, doi = {10.5114/aoms.2019.86183}, urldate = {2026-08-18}, abstract = {Introduction Gefitinib, well known as a new antitumor agent, has been applied in various cancers such as oral squamous cell carcinoma (OSCC). However, most patients eventually acquire resistance to gefitinib, and the molecular mechanism of gefitinib resistance is not well described. Bone marrow stromal cell antigen 2 (BST2) has been reported to promote tumor cell growth and confer chemotherapy resistance in various cancers. However, the roles of BST2 in OSCC still need to be fully understood. Material and methods We determined the expression of BST2 in OSCC tissues using qRT-PCR, immunohistochemistry and western blot. Next, we used MTT assay, flow cytometry and western blot to determine the roles of BST2 in OSCC cell proliferation, cycle progression and apoptosis, respectively. Furthermore, we evaluated the effect of BST2 on gefitinib resistance in OSCC cells and explored the related molecular mechanism. Results BST2 expression was up-regulated in OSCC tissues compared with the adjacent normal tissues. BST2 overexpression significantly enhanced OSCC cell proliferation, mediated the cell cycle progression and inhibited cell apoptosis. Additionally, the results showed that BST2 overexpression effectively induced gefitinib resistance in OSCC cells. Subsequent analysis revealed that the underlying mechanism was associated with activation of the EGFR pathway. Conclusions Our study indicated that BST2 promoted growth and induced gefitinib resistance in OSCC cells, at least partially, through regulating the EGFR pathway. Thus, BST2 could be used as a therapeutic target for gefitinib resistance in OSCC.}, pmcid = {PMC8641506}, pmid = {34900059}, file = {C:\Users\adama\Zotero\storage\D7EPENCV\Jin et al. - 2019 - BST2 promotes growth and induces gefitinib resistance in oral squamous cell carcinoma via regulating.pdf} } @article{johnsonIFI16RestrictsHSV12014, title = {{{IFI16 Restricts HSV-1 Replication}} by {{Accumulating}} on the {{HSV-1 Genome}}, {{Repressing HSV-1 Gene Expression}}, and {{Directly}} or {{Indirectly Modulating Histone Modifications}}}, author = {Johnson, Karen E. and Bottero, Virginie and Flaherty, Stephanie and Dutta, Sujoy and Singh, Vivek Vikram and Chandran, Bala}, editor = {Everett, Roger D.}, year = 2014, month = nov, journal = {PLoS Pathogens}, volume = {10}, number = {11}, pages = {e1004503}, issn = {1553-7374}, doi = {10.1371/journal.ppat.1004503}, urldate = {2026-08-18}, langid = {english}, pmcid = {PMC4223080}, pmid = {25375629}, file = {C:\Users\adama\Zotero\storage\L7EVQJXT\Johnson et al. - 2014 - IFI16 Restricts HSV-1 Replication by Accumulating on the HSV-1 Genome, Repressing HSV-1 Gene Express.pdf} } @article{klugeSnapShotAntiviralRestriction2015, title = {{{SnapShot}}: {{Antiviral Restriction Factors}}}, shorttitle = {{{SnapShot}}}, author = {Kluge, Silvia F. and Sauter, Daniel and Kirchhoff, Frank}, year = 2015, month = oct, journal = {Cell}, volume = {163}, number = {3}, pages = {774-774.e1}, issn = {00928674}, doi = {10.1016/j.cell.2015.10.019}, urldate = {2026-08-18}, copyright = {https://www.elsevier.com/tdm/userlicense/1.0/}, langid = {english}, pmid = {26496613} } @article{leeCharacterizationInteractionTrim282018, title = {Characterization of Interaction between {{Trim28}} and {{YY1}} in Silencing Proviral {{DNA}} of {{Moloney}} Murine Leukemia Virus}, author = {Lee, Andreia and Cing{\"O}z, Oya and Sabo, Yosef and Goff, Stephen P.}, year = 2018, month = mar, journal = {Virology}, volume = {516}, pages = {165--175}, issn = {00426822}, doi = {10.1016/j.virol.2018.01.012}, urldate = {2026-08-18}, langid = {english}, pmcid = {PMC8456507}, pmid = {29407374}, file = {C:\Users\adama\Zotero\storage\Z6H9HYHJ\Lee et al. - 2018 - Characterization of interaction between Trim28 and YY1 in silencing proviral DNA of Moloney murine l.pdf} } @article{legrandSAMD9LActsAntiviral2024, title = {{{SAMD9L}} Acts as an Antiviral Factor against {{HIV-1}} and Primate Lentiviruses by Restricting Viral and Cellular Translation}, author = {Legrand, Alexandre and Dahoui, Clara and De La Myre Mory, Cl{\'e}ment and Noy, Kodie and Guiguettaz, Laura and Versapuech, Margaux and Loyer, Clara and Pillon, Margaux and Wcislo, M{\'e}gane and Gu{\'e}guen, Laurent and {Berlioz-Torrent}, Clarisse and Cimarelli, Andrea and Mateo, Mathieu and Fiorini, Francesca and Ricci, Emiliano P. and Etienne, Lucie}, editor = {Xie, Xuping}, year = 2024, month = jul, journal = {PLOS Biology}, volume = {22}, number = {7}, pages = {e3002696}, issn = {1545-7885}, doi = {10.1371/journal.pbio.3002696}, urldate = {2026-08-18}, abstract = {Sterile alpha motif domain-containing proteins 9 and 9-like (SAMD9/9L) are associated with life-threatening genetic diseases in humans and are restriction factors of poxviruses. Yet, their cellular function and the extent of their antiviral role are poorly known. Here, we found that interferon-stimulated human SAMD9L restricts HIV-1 in the late phases of replication, at the posttranscriptional and prematuration steps, impacting viral translation and, possibly, endosomal trafficking. Surprisingly, the paralog SAMD9 exerted an opposite effect, enhancing HIV-1. More broadly, we showed that SAMD9L restricts primate lentiviruses, but not a gammaretrovirus (MLV), nor 2 RNA viruses (arenavirus MOPV and rhabdovirus VSV). Using structural modeling and mutagenesis of SAMD9L, we identified a conserved Schlafen-like active site necessary for HIV-1 restriction by human and a rodent SAMD9L. By testing a gain-of-function constitutively active variant from patients with SAMD9L-associated autoinflammatory disease, we determined that SAMD9L pathogenic functions also depend on the Schlafen-like active site. Finally, we found that the constitutively active SAMD9L strongly inhibited HIV, MLV, and, to a lesser extent, MOPV. This suggests that the virus-specific effect of SAMD9L may involve its differential activation/sensing and the virus ability to evade from SAMD9L restriction. Overall, our study identifies SAMD9L as an HIV-1 antiviral factor from the cell autonomous immunity and deciphers host determinants underlying the translational repression. This provides novel links and therapeutic avenues against viral infections and genetic diseases.}, langid = {english}, pmcid = {PMC11221667}, pmid = {38959200}, file = {C:\Users\adama\Zotero\storage\7UWHS3WU\Legrand et al. - 2024 - SAMD9L acts as an antiviral factor against HIV-1 and primate lentiviruses by restricting viral and c.pdf} } @article{leonhardtAntiviralHIV1SERINC2023, title = {Antiviral {{HIV-1 SERINC}} Restriction Factors Disrupt Virus Membrane Asymmetry}, author = {Leonhardt, Susan A. and Purdy, Michael D. and Grover, Jonathan R. and Yang, Ziwei and Poulos, Sandra and McIntire, William E. and Tatham, Elizabeth A. and Erramilli, Satchal K. and Nosol, Kamil and Lai, Kin Kui and Ding, Shilei and Lu, Maolin and Uchil, Pradeep D. and Finzi, Andr{\'e}s and Rein, Alan and Kossiakoff, Anthony A. and Mothes, Walther and Yeager, Mark}, year = 2023, month = jul, journal = {Nature Communications}, volume = {14}, number = {1}, pages = {4368}, issn = {2041-1723}, doi = {10.1038/s41467-023-39262-2}, urldate = {2026-08-18}, abstract = {Abstract The host proteins SERINC3 and SERINC5 are HIV-1 restriction factors that reduce infectivity when incorporated into the viral envelope. The HIV-1 accessory protein Nef abrogates incorporation of SERINCs via binding to intracellular loop 4 (ICL4). Here, we determine cryoEM maps of full-length human SERINC3 and an ICL4 deletion construct, which reveal that hSERINC3 is comprised of two {$\alpha$}-helical bundles connected by a\,\textasciitilde\,40-residue, highly tilted, ``crossmember'' helix. The design resembles non-ATP-dependent lipid transporters. Consistently, purified hSERINCs reconstituted into proteoliposomes induce flipping of phosphatidylserine (PS), phosphatidylethanolamine and phosphatidylcholine. Furthermore, SERINC3, SERINC5 and the scramblase TMEM16F expose PS on the surface of HIV-1 and reduce infectivity, with similar results in MLV. SERINC effects in HIV-1 and MLV are counteracted by Nef and GlycoGag, respectively. Our results demonstrate that SERINCs are membrane transporters that flip lipids, resulting in a loss of membrane asymmetry that is strongly correlated with changes in Env conformation and loss of infectivity.}, langid = {english}, pmcid = {PMC10359404}, pmid = {37474505}, file = {C:\Users\adama\Zotero\storage\CVEGNKFK\Leonhardt et al. - 2023 - Antiviral HIV-1 SERINC restriction factors disrupt virus membrane asymmetry.pdf} } @article{liExpressionMxAProtein2020, title = {Expression of {{MxA Protein}} in {{Triple Negative Breast Cancer}} and Its {{Relationship}} with {{Prognosis}}}, author = {Li, Jinmei and Sun, Jirui and Chen, Hong and Ma, Qiushuang and Zhang, Jinku}, year = 2020, month = jun, journal = {Proceedings of Anticancer Research}, volume = {4}, number = {3}, issn = {2208-3553, 2208-3545}, doi = {10.26689/par.v4i3.1257}, urldate = {2026-08-18}, abstract = {Objective: To explore the expression of human myxovirus resistance protein A (MxA) in triple negative breast cancer (TNBC) and its relationship with prognosis. Methods: 144 cases of TNBC confirmed by pathology before or after surgery from January 2014 to January 2017 in the First Central Hospital of Baoding City were retrospectively collected. Western blotting was used to detect the expression of MxA protein in TNBC and adjacent breast tissues. According to the expression of MxA protein, 144 TNBC patients were divided into low MxA protein expression group (n = 91) and MxA protein high expression group (n = 53) for subsequent comparison of prognosis of patients in between these two groups. Results: The expression of MxA protein in TNBC tissue was lower than that of adjacent breast tissue, and the difference was statistically significant (P{$<$}0.05). The patients in high MxA expression group had higher loco-regional recurrence-free rate, disease-free survival (DFS) rate, and overall survival (OS) rate than those in low MxA expression group for 3 years. On the other hand, the distant metastasis rate was lower in the high expression group compared to that in the low MxA expression group, and the difference was statistically significant (P{$<$}0.05). Conclusion: In triple-negative breast cancer, high MxA expression is a potential predictor of TNBC prognosis.}, file = {C:\Users\adama\Zotero\storage\FKE9X2HT\Li et al. - 2020 - Expression of MxA Protein in Triple Negative Breast Cancer and its Relationship with Prognosis.pdf} } @article{lillyFv2IdentificationLocation1970, title = {Fv-2: {{Identification}} and {{Location}} of a {{Second Gene Governing}} the {{Spleen Focus Response}} to {{Friend Leukemia Virus}} in {{Mice}}}, shorttitle = {Fv-2}, author = {Lilly, Frank}, year = 1970, month = jul, journal = {JNCI: Journal of the National Cancer Institute}, volume = {45}, number = {1}, pages = {163--169}, issn = {0027-8874}, doi = {10.1093/jnci/45.1.163}, urldate = {2026-08-18}, abstract = {The use of 2 strains of Friend virus, the F-S strain and its BALB/c-adapted variant, the F-B strain, permitted the identification of a second major gene distinguishing the DBA/2J (susceptible to both virus strains) and C57BL (resistant to both virus strains) mouse strains with respect to their spleen focus responses to the viruses. Progeny testing of (C57BL \texttimes{} DBA/2J) \texttimes{} DBA/2J backcross females showed that the new gene, Fv-2, segregates independently of the previously identified Fv-1 gene; Fv-2, with alleles Fv-2S (susceptible) and Fv-2r (resistant), is linked to dilute in linkage group II. Expression of the Fv-1 phenotype (relative spleen-focus response to F-S virus) is suppressed by homozygosity for the recessive Fv-2r allele, but the Fv-1 locus appears to exert little influence on the expression of the Fv-2 phenotype (spleen focus response to F-B virus). The possible relevance of these findings to the concept that spleen focus formation by Friend virus requires a helper virus is discussed.} } @article{liuPSGL1InhibitsHIV12020, title = {{{PSGL-1}} Inhibits {{HIV-1}} Infection by Restricting Actin Dynamics and Sequestering {{HIV}} Envelope Proteins}, author = {Liu, Ying and Song, Yutong and Zhang, Siyu and Diao, Min and Huang, Shanjin and Li, Sai and Tan, Xu}, year = 2020, month = aug, journal = {Cell Discovery}, volume = {6}, number = {1}, pages = {53}, issn = {2056-5968}, doi = {10.1038/s41421-020-0184-9}, urldate = {2026-08-18}, abstract = {Abstract PSGL-1 has recently been identified as an HIV restriction factor that inhibits HIV DNA synthesis and more potently, virion infectivity. But the underlying mechanisms of these inhibitions are unknown. Here we show that PSGL-1 directly binds to cellular actin filaments (F-actin) to restrict actin dynamics, which leads to inhibition of HIV DNA synthesis. PSGL-1 is incorporated into nascent virions and restricts actin dynamics in the virions, which partially accounts for the inhibition of virion infectivity. More potently, PSGL-1 inhibits incorporation of Env proteins into nascent virions, causing a loss of envelope spikes on the virions as shown by Cryo-electron microscopy and super-resolution imaging. This loss is associated with a profound defect in viral entry. Mechanistically, PSGL-1 binds gp41 and sequesters gp41 at the plasma membrane, explaining the inhibition of Env incorporation in nascent virions. PSGL-1's dual anti-HIV mechanisms represent novel strategies of human cells to defend against HIV infection.}, langid = {english}, pmcid = {PMC7400672}, pmid = {32802403}, file = {C:\Users\adama\Zotero\storage\WNQF8SFL\Liu et al. - 2020 - PSGL-1 inhibits HIV-1 infection by restricting actin dynamics and sequestering HIV envelope proteins.pdf} } @article{luIFI16PromotesProgression2024, title = {{{IFI16}} Promotes the Progression of Clear Cell Renal Cell Carcinoma through the {{IL6}}/{{PI3K}}/{{AKT}} Axis}, author = {Lu, Ke and Zhao, Yan and Li, Yu and Fu, Zhenyu and Chen, Yongchang and Kong, Ying and Li, Gang}, year = 2024, month = jun, journal = {Journal of Translational Medicine}, volume = {22}, number = {1}, pages = {533}, issn = {1479-5876}, doi = {10.1186/s12967-024-05354-w}, urldate = {2026-08-18}, abstract = {Abstract Background Clear cell renal cell carcinoma (ccRCC) is a common disease in the urinary system, with a high incidence and poor prognosis in advanced stages. Although {$\gamma$}-interferon-inducible protein 16 (IFI16) has been reported to play a role in various tumors, its involvement in ccRCC remains poorly documented, and the molecular mechanisms are not yet clear. Methods We conducted bioinformatics analysis to study the expression of IFI16 in ccRCC using public databases. Additionally, we analyzed and validated clinical specimens that we collected. Subsequently, we explored the impact of IFI16 on ccRCC cell proliferation, migration, and invasion through in vitro and in vivo experiments. Furthermore, we predicted downstream molecules and pathways using transcriptome analysis and confirmed them through follow-up experimental validation. Results IFI16 was significantly upregulated in ccRCC tissue and correlated with poor patient prognosis. In vitro, IFI16 promoted ccRCC cell proliferation, migration, and invasion, while in vivo, it facilitated subcutaneous tumor growth and the formation of lung metastatic foci. Knocking down IFI16 suppressed its oncogenic function. At the molecular level, IFI16 promoted the transcription and translation of IL6, subsequently activating the PI3K/AKT signaling pathway and inducing epithelial-mesenchymal transition (EMT). Conclusion IFI16 induced EMT through the IL6/PI3K/AKT axis, promoting the progression of ccRCC.}, langid = {english}, pmcid = {PMC11149187}, pmid = {38831470}, file = {C:\Users\adama\Zotero\storage\WM4CTWAZ\Lu et al. - 2024 - IFI16 promotes the progression of clear cell renal cell carcinoma through the IL6PI3KAKT axis.pdf} } @article{maggHeterozygousOAS1Gainoffunction2021, title = {Heterozygous {{{\emph{OAS1}}}} Gain-of-Function Variants Cause an Autoinflammatory Immunodeficiency}, author = {Magg, Thomas and Okano, Tsubasa and Koenig, Lars M. and Boehmer, Daniel F.R. and Schwartz, Samantha L. and Inoue, Kento and Heimall, Jennifer and Licciardi, Francesco and {Ley-Zaporozhan}, Julia and Ferdman, Ronald M. and {Caballero-Oteyza}, Andr{\'e}s and Park, Esther N. and Calderon, Brenda M. and Dey, Debayan and Kanegane, Hirokazu and Cho, Kazutoshi and Montin, Davide and Reiter, Karl and Griese, Matthias and Albert, Michael H. and Rohlfs, Meino and Gray, Paul and Walz, Christoph and Conn, Graeme L. and Sullivan, Kathleen E. and Klein, Christoph and Morio, Tomohiro and Hauck, Fabian}, year = 2021, month = jun, journal = {Science Immunology}, volume = {6}, number = {60}, pages = {eabf9564}, issn = {2470-9468}, doi = {10.1126/sciimmunol.abf9564}, urldate = {2026-08-18}, abstract = {OAS1-GOF/RNase L--mediated RNA cleavage caused an interferon-induced hyperinflammatory monocyte and B cell immunodeficiency. , Mutated OAS1 leads to immunodeficiency Inborn errors of immunity can result in autoinflammatory immunodeficiencies. Type I interferon--inducible oligoadenylate synthetase 1 (OAS1) can initiate antiviral immune responses and is linked to pulmonary alveolar proteinosis with hypogammaglobulinemia. Here, Magg et al. identified four heterozygous OAS1 gain-of-function mutations that cause a polymorphic immunodeficiency in six patients. The OAS1 mutants induced functional and transcriptomic alterations in monocytes, B cells, and T cells, which related to RNase L--dependent cellular dysfunction, apoptosis, protein translation arrest, and cellular RNA degradation. These deficiencies correlated to the altered structure of the OAS1 mutants. Some of these OAS1 gain-of-function patients were cured by hematopoietic stem cell transplantation, suggesting that these immune defects directly contributed to the disease phenotypes. These data give further insight into a rare autoinflammatory immunodeficiency. , Analysis of autoinflammatory and immunodeficiency disorders elucidates human immunity and fosters the development of targeted therapies. Oligoadenylate synthetase 1 is a type I interferon--induced, intracellular double-stranded RNA (dsRNA) sensor that generates 2{$\prime$}-5{$\prime$}-oligoadenylate to activate ribonuclease L (RNase L) as a means of antiviral defense. We identified four de novo heterozygous OAS1 gain-of-function variants in six patients with a polymorphic autoinflammatory immunodeficiency characterized by recurrent fever, dermatitis, inflammatory bowel disease, pulmonary alveolar proteinosis, and hypogammaglobulinemia. To establish causality, we applied genetic, molecular dynamics simulation, biochemical, and cellular functional analyses in heterologous, autologous, and inducible pluripotent stem cell--derived macrophages and/or monocytes and B cells. We found that upon interferon-induced expression, OAS1 variant proteins displayed dsRNA-independent activity, which resulted in RNase L--mediated RNA cleavage, transcriptomic alteration, translational arrest, and dysfunction and apoptosis of monocytes, macrophages, and B cells. RNase L inhibition with curcumin modulated and allogeneic hematopoietic cell transplantation cured the disorder. Together, these data suggest that human OAS1 is a regulator of interferon-induced hyperinflammatory monocyte, macrophage, and B cell pathophysiology.}, langid = {english}, pmcid = {PMC8392508}, pmid = {34145065} } @article{maharanaSAMHD1ControlsInnate2022, title = {{{SAMHD1}} Controls Innate Immunity by Regulating Condensation of Immunogenic Self {{RNA}}}, author = {Maharana, Shovamayee and Kretschmer, Stefanie and Hunger, Susan and Yan, Xiao and Kuster, David and Traikov, Sofia and Zillinger, Thomas and Gentzel, Marc and Elangovan, Shobha and Dasgupta, Padmanava and Chappidi, Nagaraja and Lucas, Nadja and Maser, Katharina Isabell and Maatz, Henrike and Rapp, Alexander and Marchand, Virginie and Chang, Young-Tae and Motorin, Yuri and Hubner, Norbert and Hartmann, Gunther and Hyman, Anthony A. and Alberti, Simon and {Lee-Kirsch}, Min Ae}, year = 2022, month = oct, journal = {Molecular Cell}, volume = {82}, number = {19}, pages = {3712-3728.e10}, issn = {10972765}, doi = {10.1016/j.molcel.2022.08.031}, urldate = {2026-08-18}, langid = {english}, pmid = {36150385}, file = {C:\Users\adama\Zotero\storage\JPXSK47P\Maharana et al. - 2022 - SAMHD1 controls innate immunity by regulating condensation of immunogenic self RNA.pdf} } @article{manjunathAPOBEC3BDrivesPKRmediated2023, title = {{{APOBEC3B}} Drives {{PKR-mediated}} Translation Shutdown and Protects Stress Granules in Response to Viral Infection}, author = {Manjunath, Lavanya and Oh, Sunwoo and Ortega, Pedro and Bouin, Alexis and Bournique, Elodie and Sanchez, Ambrocio and Martensen, Pia M{\o}ller and Auerbach, Ashley A. and Becker, Jordan T. and Seldin, Marcus and Harris, Reuben S. and Semler, Bert L. and Buisson, R{\'e}mi}, year = 2023, month = feb, journal = {Nature Communications}, volume = {14}, number = {1}, pages = {820}, issn = {2041-1723}, doi = {10.1038/s41467-023-36445-9}, urldate = {2026-08-18}, abstract = {Abstract Double-stranded RNA produced during viral replication and transcription activates both protein kinase R (PKR) and ribonuclease L (RNase L), which limits viral gene expression and replication through host shutoff of translation. In this study, we find that APOBEC3B forms a complex with PABPC1 to stimulate PKR and counterbalances the PKR-suppressing activity of ADAR1 in response to infection by many types of viruses. This leads to translational blockage and the formation of stress granules. Furthermore, we show that APOBEC3B localizes to stress granules through the interaction with PABPC1. APOBEC3B facilitates the formation of protein-RNA condensates with stress granule assembly factor (G3BP1) by protecting mRNA associated with stress granules from RNAse L-induced RNA cleavage during viral infection. These results not only reveal that APOBEC3B is a key regulator of different steps of the innate immune response throughout viral infection but also highlight an alternative mechanism by which APOBEC3B can impact virus replication without editing viral genomes.}, langid = {english}, pmcid = {PMC9925369}, pmid = {36781883}, file = {C:\Users\adama\Zotero\storage\BXKQFTJZ\Manjunath et al. - 2023 - APOBEC3B drives PKR-mediated translation shutdown and protects stress granules in response to viral.pdf} } @article{mengParalogousPairMammalian2018, title = {A Paralogous Pair of Mammalian Host Restriction Factors Form a Critical Host Barrier against Poxvirus Infection}, author = {Meng, Xiangzhi and Zhang, Fushun and Yan, Bo and Si, Chuanping and Honda, Hiroaki and Nagamachi, Akiko and Sun, Lu-Zhe and Xiang, Yan}, editor = {Sutter, Gerd}, year = 2018, month = feb, journal = {PLOS Pathogens}, volume = {14}, number = {2}, pages = {e1006884}, issn = {1553-7374}, doi = {10.1371/journal.ppat.1006884}, urldate = {2026-08-18}, langid = {english}, pmcid = {PMC5831749}, pmid = {29447249}, file = {C:\Users\adama\Zotero\storage\2PGVKVHK\Meng et al. - 2018 - A paralogous pair of mammalian host restriction factors form a critical host barrier against poxviru.pdf} } @article{morelPKRDoubleStranded2009, title = {{{PKR}}, the Double Stranded {{RNA}}-dependent Protein Kinase as a Critical Target in {{Alzheimer}}'s Disease}, author = {Morel, Milena and Couturier, Julien and Lafay-Chebassier, Claire and Paccalin, Marc and Page, Guyl{\`e}ne}, year = 2009, month = aug, journal = {Journal of Cellular and Molecular Medicine}, volume = {13}, number = {8a}, pages = {1476--1488}, issn = {1582-1838, 1582-4934}, doi = {10.1111/j.1582-4934.2009.00849.x}, urldate = {2026-08-18}, abstract = {Abstract Introduction Control of translation Dysfunctions of protein synthesis mediated by PKR- and mTOR-dependent signalling pathways Crosslink between the up-regulation of PKR/eIF2{$\alpha$} and the down-regulation of mTOR/RS6K in AD PKR: a potential biomarker of AD diagnosis Conclusion and perspectives Amyloid {$\beta$}-peptide (A{$\beta$}) deposits and neurofibrillary tangles are key hallmarks in Alzheimer's disease (AD). A{$\beta$} stimulates many signal transducers involved in the neuronal death. However, many mechanisms remain to be elucidated because no definitive therapy of AD exists. Some studies have focused on the control of translation which involves eIF2 and eIF4E, main eukaryotic factors of initiation. The availability of these factors depends on the activation of the double-stranded RNA-dependent protein kinase (PKR) and the mammalian target of rapamycin (mTOR), respectively. mTOR positively regulates the translation while PKR results in a protein synthesis shutdown. Many studies demonstrated that the PKR signalling pathway is up-regulated in cellular and animal models of AD and in the brain of AD patients. Interestingly, our results showed that phosphorylated PKR and eIF2{$\alpha$} levels were significantly increased in lymphocytes of AD patients. These modifications were significantly correlated with cognitive and memory test scores performed in AD patients. On the contrary, the mTOR signalling pathway is down-regulated in cellular and animal models of AD. Recently, we showed that p53, regulated protein in development and DNA damage response 1 and tuberous sclerosis complex 2 could represent molecular links between PKR and mTOR signalling pathways. PKR could be an early biomarker of the neuronal death and a critical target for a therapeutic programme in AD.}, copyright = {http://onlinelibrary.wiley.com/termsAndConditions\#vor}, langid = {english}, pmcid = {PMC3828860}, pmid = {19602051}, file = {C:\Users\adama\Zotero\storage\6PDLZMIN\Morel et al. - 2009 - PKR, the double stranded RNA‐dependent protein kinase as a critical target in Alzheimer's disease.pdf} } @article{naumannDNADeaminationRequired2023, title = {{{DNA Deamination Is Required}} for {{Human APOBEC3A-Driven Hepatocellular Carcinoma In Vivo}}}, author = {Naumann, Jordan A. and Argyris, Prokopios P. and Carpenter, Michael A. and Gupta, Harshita B. and Chen, Yanjun and Temiz, Nuri A. and Zhou, Yufan and Durfee, Cameron and Proehl, Joshua and Koniar, Brenda L. and Conticello, Silvestro G. and Largaespada, David A. and Brown, William L. and Aihara, Hideki and Vogel, Rachel I. and Harris, Reuben S.}, year = 2023, month = may, journal = {International Journal of Molecular Sciences}, volume = {24}, number = {11}, pages = {9305}, issn = {1422-0067}, doi = {10.3390/ijms24119305}, urldate = {2026-08-18}, abstract = {Although the APOBEC3 family of single-stranded DNA cytosine deaminases is well-known for its antiviral factors, these enzymes are rapidly gaining attention as prominent sources of mutation in cancer. APOBEC3{$\prime$}s signature single-base substitutions, C-to-T and C-to-G in TCA and TCT motifs, are evident in over 70\% of human malignancies and dominate the mutational landscape of numerous individual tumors. Recent murine studies have established cause-and-effect relationships, with both human APOBEC3A and APOBEC3B proving capable of promoting tumor formation in vivo. Here, we investigate the molecular mechanism of APOBEC3A-driven tumor development using the murine Fah liver complementation and regeneration system. First, we show that APOBEC3A alone is capable of driving tumor development (without Tp53 knockdown as utilized in prior studies). Second, we show that the catalytic glutamic acid residue of APOBEC3A (E72) is required for tumor formation. Third, we show that an APOBEC3A separation-of-function mutant with compromised DNA deamination activity and wildtype RNA-editing activity is defective in promoting tumor formation. Collectively, these results demonstrate that APOBEC3A is a ``master driver'' that fuels tumor formation through a DNA deamination-dependent mechanism.}, langid = {english}, pmcid = {PMC10253583}, pmid = {37298259} } @article{okamotoSLFN11PromotesStalled2021a, title = {{{{\emph{SLFN11}}}} Promotes Stalled Fork Degradation That Underlies the Phenotype in {{Fanconi}} Anemia Cells}, author = {Okamoto, Yusuke and Abe, Masako and Mu, Anfeng and Tempaku, Yasuko and Rogers, Colette B. and Mochizuki, Ayako L. and Katsuki, Yoko and Kanemaki, Masato T. and {Takaori-Kondo}, Akifumi and Sobeck, Alexandra and Bielinsky, Anja-Katrin and Takata, Minoru}, year = 2021, month = jan, journal = {Blood}, volume = {137}, number = {3}, pages = {336--348}, issn = {0006-4971, 1528-0020}, doi = {10.1182/blood.2019003782}, urldate = {2026-08-18}, abstract = {Abstract Fanconi anemia (FA) is a hereditary disorder caused by mutations in any 1 of 22 FA genes. The disease is characterized by hypersensitivity to interstrand crosslink (ICL) inducers such as mitomycin C (MMC). In addition to promoting ICL repair, FA proteins such as RAD51, BRCA2, or FANCD2 protect stalled replication forks from nucleolytic degradation during replication stress, which may have a profound impact on FA pathophysiology. Recent studies showed that expression of the putative DNA/RNA helicase SLFN11 in cancer cells correlates with cell death on chemotherapeutic treatment. However, the underlying mechanisms of SLFN11-mediated DNA damage sensitivity remain unclear. Because SLFN11 expression is high in hematopoietic stem cells, we hypothesized that SLFN11 depletion might ameliorate the phenotypes of FA cells. Here we report that SLFN11 knockdown in the FA patient-derived FANCD2-deficient PD20 cell line improved cell survival on treatment with ICL inducers. FANCD2-/-SLFN11-/- HAP1 cells also displayed phenotypic rescue, including reduced levels of MMC-induced chromosome breakage compared with FANCD2-/- cells. Importantly, we found that SLFN11 promotes extensive fork degradation in FANCD2-/- cells. The degradation process is mediated by the nucleases MRE11 or DNA2 and depends on the SLFN11 ATPase activity. This observation was accompanied by an increased RAD51 binding at stalled forks, consistent with the role of RAD51 antagonizing nuclease recruitment and subsequent fork degradation. Suppression of SLFN11 protects nascent DNA tracts even in wild-type cells. We conclude that SLFN11 destabilizes stalled replication forks, and this function may contribute to the attrition of hematopoietic stem cells in FA.}, langid = {english}, pmcid = {PMC7819757}, pmid = {32735670} } @article{orrisGuaninecontainingSsDNARNA2023, title = {Guanine-Containing {{ssDNA}} and {{RNA}} Induce Dimeric and Tetrameric Structural Forms of {{SAMHD1}}}, author = {Orris, Benjamin and Sung, Min Woo and Bhat, Shridhar and Xu, Yingrong and Huynh, Kevin W and Han, Seungil and Johnson, Darren C and Bosbach, Benedikt and Shields, David J and Stivers, James T}, year = 2023, month = dec, journal = {Nucleic Acids Research}, volume = {51}, number = {22}, pages = {12443--12458}, issn = {0305-1048, 1362-4962}, doi = {10.1093/nar/gkad971}, urldate = {2026-08-18}, abstract = {Abstract The dNTPase activity of tetrameric SAM and HD domain containing deoxynucleoside triphosphate triphosphohydrolase 1 (SAMHD1) plays a critical role in cellular dNTP regulation. SAMHD1 also associates with stalled DNA replication forks, DNA repair foci, ssRNA~and telomeres. The above functions require nucleic acid binding by SAMHD1, which may be modulated by its oligomeric state. Here we establish in cryo-EM and biochemical studies that the guanine-specific A1 activator site of each SAMHD1 monomer is used to target the enzyme to guanine nucleotides within single-stranded (ss) DNA and RNA. Remarkably, nucleic acid strands containing a single guanine base induce dimeric SAMHD1, while two or more guanines with {$\sim$}20 nucleotide spacing induce a tetrameric form. A cryo-EM structure of ssRNA-bound tetrameric SAMHD1 shows how ssRNA strands bridge two SAMHD1 dimers and stabilize the structure. This ssRNA-bound tetramer is inactive with respect to dNTPase and RNase activity.}, copyright = {https://creativecommons.org/licenses/by-nc/4.0/}, langid = {english}, pmcid = {PMC10711556}, pmid = {37930833} } @article{ozcanBendingBST2Coiledcoil2017, title = {Bending of the {{BST}}-2 Coiled-coil during Viral Budding}, author = {Ozcan, Kadir A. and Berndsen, Christopher E.}, year = 2017, month = nov, journal = {Proteins: Structure, Function, and Bioinformatics}, volume = {85}, number = {11}, pages = {2081--2087}, issn = {0887-3585, 1097-0134}, doi = {10.1002/prot.25362}, urldate = {2026-08-18}, abstract = {Abstract BST-2/tetherin is a human extracellular transmembrane protein that serves as a host defense factor against HIV-1 and other viruses by inhibiting viral spreading. Structurally, BST-2 is a homo-dimeric coiled-coil that is connected to the host cell membrane by N and C terminal transmembrane anchors. The C-terminal membrane anchor of BST-2 is inserted into the budding virus while the N-terminal membrane anchor remains in the host cell membrane creating a viral tether. The structural mechanism of viral budding and tethering as mediated by BST-2 is not clear. To more fully describe the mechanism of viral tethering, we created a model of BST-2 embedded in a membrane and used steered molecular dynamics to simulate the transition from the host cell membrane associated form to the cell-virus membrane bridging form. We observed that BST-2 did not transition as a rigid structure, but instead bent at positions with a reduced interface between the helices of the coiled-coil. The simulations for the human BST-2 were then compared with simulations on the mouse homolog, which has no apparent weak spots. We observed that the mouse homolog spread the bending across the ectodomain, rather than breaking at discrete points as observed with the human homolog. These simulations support previous biochemical and cellular work suggesting some flexibility in the coiled-coil is necessary for viral tethering, while also highlighting how subtle changes in protein sequence can influence the dynamics and stability of proteins with overall similar structure.}, copyright = {http://onlinelibrary.wiley.com/termsAndConditions\#am}, langid = {english}, pmid = {28779494} } @article{russellSAMD9LAutoinflammatoryAtaxia2021, title = {{{SAMD9L}} Autoinflammatory or Ataxia Pancytopenia Disease Mutations Activate Cell-Autonomous Translational Repression}, author = {Russell, Amanda J. and Gray, Paul E. and Ziegler, John B. and Kim, Yae Jean and Smith, Sandy and Sewell, William A. and Goodnow, Christopher C.}, year = 2021, month = aug, journal = {Proceedings of the National Academy of Sciences}, volume = {118}, number = {34}, pages = {e2110190118}, issn = {0027-8424, 1091-6490}, doi = {10.1073/pnas.2110190118}, urldate = {2026-08-18}, abstract = {Significance The experiments here advance understanding of the function of the SAMD9L gene and protein in innate immune mechanisms in resisting virus infection and in the pathogenesis of inflammatory, hematological, and neurological disorders. The clinical syndrome defined in two children with de novo truncating SAMD9L mutations expands the phenotypes in this newly recognized autoinflammatory disorder. Analysis of cells expressing normal or mutant SAMD9L reveals the protein represses protein translation, with the truncating mutations greatly exaggerating this activity. The experiments find equally potent gain of function caused by the truncating mutations or a recurrent missense mutation associated with clinically milder ataxia and pancytopenia syndromes, demonstrating that diverse clinical manifestations can arise from mutations that appear cell-biologically equivalent. , Sterile {$\alpha$} motif domain-containing protein 9-like (SAMD9L) is encoded by a hallmark interferon-induced gene with a role in controlling virus replication that is not well understood. Here, we analyze SAMD9L function from the perspective of human mutations causing neonatal-onset severe autoinflammatory disease. Whole-genome sequencing of two children with leukocytoclastic panniculitis, basal ganglia calcifications, raised blood inflammatory markers, neutrophilia, anemia, thrombocytopaenia, and almost no B cells revealed heterozygous de novo SAMD9L mutations, p.Asn885Thrfs*6 and p.Lys878Serfs*13. These frameshift mutations truncate the SAMD9L protein within a domain a region of homology to the nucleotide-binding and oligomerization domain (NOD) of APAF1, {$\sim$}80 amino acids C-terminal to the Walker B motif. Single-cell analysis of human cells expressing green fluorescent protein (GFP)-SAMD9L fusion proteins revealed that enforced expression of wild-type SAMD9L repressed translation of red fluorescent protein messenger RNA and globally repressed endogenous protein translation, cell autonomously and in proportion to the level of GFP-SAMD9L in each cell. The children's truncating mutations dramatically exaggerated translational repression even at low levels of GFP-SAMD9L per cell, as did a missense Arg986Cys mutation reported recurrently as causing ataxia pancytopenia syndrome. Autoinflammatory disease associated with SAMD9L truncating mutations appears to result from an interferon-induced translational repressor whose activity goes unchecked by the loss of C-terminal domains that may normally sense virus infection.}, langid = {english}, pmcid = {PMC8403910}, pmid = {34417303} } @article{sauterCounteractionMultifunctionalRestriction2014, title = {Counteraction of the Multifunctional Restriction Factor Tetherin}, author = {Sauter, Daniel}, year = 2014, month = apr, journal = {Frontiers in Microbiology}, volume = {5}, issn = {1664-302X}, doi = {10.3389/fmicb.2014.00163}, urldate = {2026-08-18}, pmcid = {PMC3989765}, pmid = {24782851}, file = {C:\Users\adama\Zotero\storage\SVYHBMVG\Sauter - 2014 - Counteraction of the multifunctional restriction factor tetherin.pdf} } @article{schillingHumanMxBProtein2018, title = {Human {{MxB Protein Is}} a {{Pan-herpesvirus Restriction Factor}}}, author = {Schilling, Mirjam and Bulli, Lorenzo and Weigang, Sebastian and Graf, Laura and Naumann, Sebastian and Patzina, Corinna and Wagner, Valentina and Bauersfeld, Liane and Goujon, Caroline and Hengel, Hartmut and Halenius, Anne and Ruzsics, Zsolt and Schaller, Torsten and Kochs, Georg}, editor = {{Sandri-Goldin}, Rozanne M.}, year = 2018, month = sep, journal = {Journal of Virology}, volume = {92}, number = {17}, pages = {e01056-18}, issn = {0022-538X, 1098-5514}, doi = {10.1128/JVI.01056-18}, urldate = {2026-08-18}, abstract = {Human herpesviruses pose a constant threat to human health. Reactivation of persisting herpesvirus infections, particularly in immunocompromised individuals and the elderly, can cause severe diseases, such as zoster, pneumonia, encephalitis, or cancer. The interferon system is relevant for the control of herpesvirus replication as exemplified by fatal disease outcomes in patients with primary immunodeficiencies. Here, we describe the interferon-induced, human MX2 gene product MxB as an efficient restriction factor of alpha-, beta-, and gammaherpesviruses. MxB has previously been described as an inhibitor of HIV-1. Importantly, our mutational analyses of MxB reveal an antiviral mechanism of herpesvirus restriction distinct from that against HIV-1. Thus, the dynamin-like MxB GTPase serves as a broadly acting intracellular restriction factor that controls retrovirus as well as herpesvirus infections. , ABSTRACT Herpesvirus infections are highly prevalent in the human population and persist for life. They are often acquired subclinically but potentially progress to life-threatening diseases in immunocompromised individuals. The interferon system is indispensable for the control of herpesviral replication. However, the responsible antiviral effector mechanisms are not well characterized. The type I interferon-induced, human myxovirus resistance 2 ( MX2 ) gene product MxB, a dynamin-like large GTPase, has recently been identified as a potent inhibitor of HIV-1. We now show that MxB also interferes with an early step of herpesvirus replication, affecting alpha-, beta-, and gammaherpesviruses before or at the time of immediate early gene expression. Defined MxB mutants influencing GTP binding and hydrolysis revealed that the effector mechanism against herpesviruses is thoroughly different from that against HIV-1. Overall, our findings demonstrate that MxB serves as a broadly acting intracellular restriction factor that controls the establishment of not only retrovirus but also herpesvirus infection of all three subfamilies. IMPORTANCE Human herpesviruses pose a constant threat to human health. Reactivation of persisting herpesvirus infections, particularly in immunocompromised individuals and the elderly, can cause severe diseases, such as zoster, pneumonia, encephalitis, or cancer. The interferon system is relevant for the control of herpesvirus replication as exemplified by fatal disease outcomes in patients with primary immunodeficiencies. Here, we describe the interferon-induced, human MX2 gene product MxB as an efficient restriction factor of alpha-, beta-, and gammaherpesviruses. MxB has previously been described as an inhibitor of HIV-1. Importantly, our mutational analyses of MxB reveal an antiviral mechanism of herpesvirus restriction distinct from that against HIV-1. Thus, the dynamin-like MxB GTPase serves as a broadly acting intracellular restriction factor that controls retrovirus as well as herpesvirus infections.}, langid = {english}, pmcid = {PMC6096802}, pmid = {29950411}, file = {C:\Users\adama\Zotero\storage\TJNR2A9K\Schilling et al. - 2018 - Human MxB Protein Is a Pan-herpesvirus Restriction Factor.pdf} } @article{serreroRestrictionFactorsRegulating2024, title = {Restriction Factors Regulating Human Herpesvirus Infections}, author = {Serrero, Manutea C. and Paludan, S{\o}ren R.}, year = 2024, month = sep, journal = {Trends in Immunology}, volume = {45}, number = {9}, pages = {662--677}, issn = {14714906}, doi = {10.1016/j.it.2024.07.010}, urldate = {2026-08-18}, langid = {english}, pmid = {39198098} } @article{shangSystematicPancancerAnalysis2023, title = {A Systematic Pan-Cancer Analysis Identifies {{TRIM28}} as an Immunological and Prognostic Predictor and Involved in Immunotherapy Resistance}, author = {Shang, Zhi and Wu, Xinqiang and Zheng, Shengfeng and Wei, Yaru and Hong, Zhe and Ye, Dingwei}, year = 2023, journal = {Journal of Cancer}, volume = {14}, number = {15}, pages = {2798--2810}, issn = {1837-9664}, doi = {10.7150/jca.86742}, urldate = {2026-08-18}, langid = {english}, pmcid = {PMC10539564}, pmid = {37781084}, file = {C:\Users\adama\Zotero\storage\B3QE9ULN\Shang et al. - 2023 - A systematic pan-cancer analysis identifies TRIM28 as an immunological and prognostic predictor and.pdf} } @article{shaoVersatilityZincFingerAntiviral2024, title = {Versatility of the {{Zinc-Finger Antiviral Protein}} ({{ZAP}}) {{As}} a {{Modulator}} of {{Viral Infections}}}, author = {Shao, Ran and Visser, Imke and Fros, Jelke J. and Yin, Xin}, year = 2024, journal = {International Journal of Biological Sciences}, volume = {20}, number = {12}, pages = {4585--4600}, issn = {1449-2288}, doi = {10.7150/ijbs.98029}, urldate = {2026-08-18}, langid = {english}, pmcid = {PMC11414379}, pmid = {39309436}, file = {C:\Users\adama\Zotero\storage\VTJSM5ZV\Shao et al. - 2024 - Versatility of the Zinc-Finger Antiviral Protein (ZAP) As a Modulator of Viral Infections.pdf} } @article{sivanHumanHostRange2018, title = {Human {{Host Range Restriction}} of the {{Vaccinia Virus C7}}/{{K1 Double Deletion Mutant Is Mediated}} by an {{Atypical Mode}} of {{Translation Inhibition}}}, author = {Sivan, Gilad and {Glushakow-Smith}, Shira G. and Katsafanas, George C. and Americo, Jeffrey L. and Moss, Bernard}, editor = {Shisler, Joanna L.}, year = 2018, month = dec, journal = {Journal of Virology}, volume = {92}, number = {23}, pages = {e01329-18}, issn = {0022-538X, 1098-5514}, doi = {10.1128/JVI.01329-18}, urldate = {2026-08-18}, abstract = {A dynamic relationship exists between viruses and their hosts in which each ostensibly attempts to exploit the other's vulnerabilities. A window is opened into the established condition, which evolved over millennia, if loss-of-function mutations occur in either the virus or host. Thus, the inability of viral host range mutants to replicate in specific cells can be overcome by identifying and inactivating the opposing cellular gene. Here, we investigated a C7/K1 host range mutant of vaccinia virus in which the cellular gene SAMD9 serves as the principal host restriction factor. Host restriction was triggered early in infection and manifested as a block in translation of viral mRNAs. Features of the block include inhibition of cap-dependent and internal ribosome entry site-mediated translation, sequestration of viral RNA, and inability to overcome the inhibition by inactivation of protein kinase R, ribonuclease L, or G3 binding proteins, suggesting a novel mechanism of host restriction. , ABSTRACT Replication of vaccinia virus in human cells depends on the viral C7 or K1 protein. A previous human genome-wide short interfering RNA (siRNA) screen with a C7/K1 double deletion mutant revealed SAMD9 as a principal host range restriction factor along with additional candidates, including WDR6 and FTSJ1. To compare their abilities to restrict replication, the cellular genes were individually inactivated by CRISPR/Cas9 mutagenesis. The C7/K1 deletion mutant exhibited enhanced replication in each knockout (KO) cell line but reached wild-type levels only in SAMD9 KO cells. SAMD9 was not depleted in either WDR6 or FTSJ1 KO cells, suggesting less efficient alternative rescue mechanisms. Using the SAMD9 KO cells as controls, we verified a specific block in host and viral intermediate and late protein synthesis in HeLa cells and demonstrated that the inhibition could be triggered by events preceding viral DNA replication. Inhibition of cap-dependent and -independent protein synthesis occurred primarily at the translational level, as supported by DNA and mRNA transfection experiments. Concurrent with collapse of polyribosomes, viral mRNA was predominantly in 80S and lighter ribonucleoprotein fractions. We confirmed the accumulation of cytoplasmic granules in HeLa cells infected with the C7/K1 deletion mutant and further showed that viral mRNA was sequestered with SAMD9. RNA granules were still detected in G3BP KO U2OS cells, which remained nonpermissive for the C7/K1 deletion mutant. Inhibition of cap-dependent and internal ribosome entry site-mediated translation, sequestration of viral mRNA, and failure of PKR, RNase L, or G3BP KO cells to restore protein synthesis support an unusual mechanism of host restriction. IMPORTANCE A dynamic relationship exists between viruses and their hosts in which each ostensibly attempts to exploit the other's vulnerabilities. A window is opened into the established condition, which evolved over millennia, if loss-of-function mutations occur in either the virus or host. Thus, the inability of viral host range mutants to replicate in specific cells can be overcome by identifying and inactivating the opposing cellular gene. Here, we investigated a C7/K1 host range mutant of vaccinia virus in which the cellular gene SAMD9 serves as the principal host restriction factor. Host restriction was triggered early in infection and manifested as a block in translation of viral mRNAs. Features of the block include inhibition of cap-dependent and internal ribosome entry site-mediated translation, sequestration of viral RNA, and inability to overcome the inhibition by inactivation of protein kinase R, ribonuclease L, or G3 binding proteins, suggesting a novel mechanism of host restriction.}, langid = {english}, pmcid = {PMC6232495}, pmid = {30209174} } @article{suntharalinghamEmergingPhenotypesLinked2022, title = {Emerging Phenotypes Linked to Variants in {{SAMD9}} and {{MIRAGE}} Syndrome}, author = {Suntharalingham, Jenifer P. and Ishida, Miho and Del Valle, Ignacio and Stalman, Susanne E. and Solanky, Nita and Wakeling, Emma and Moore, Gudrun E. and Achermann, John C. and Buonocore, Federica}, year = 2022, month = aug, journal = {Frontiers in Endocrinology}, volume = {13}, pages = {953707}, issn = {1664-2392}, doi = {10.3389/fendo.2022.953707}, urldate = {2026-08-18}, abstract = {Background Heterozygous de novo variants in SAMD9 cause MIRAGE syndrome, a complex multisystem disorder involving Myelodysplasia, Infection, Restriction of growth, Adrenal hypoplasia, Genital phenotypes, and Enteropathy. The range of additional clinical associations is expanding and includes disrupted placental development, poor post-natal growth and endocrine features. Increasingly, milder phenotypic features such as hypospadias in small for gestational age (SGA) boys and normal adrenal function are reported. Some children present with isolated myelodysplastic syndrome (MDS/monosomy 7) without MIRAGE features. Objective We aimed to investigate: 1) the range of reported SAMD9 variants, clinical features, and possible genotype-phenotype correlations; 2) whether SAMD9 disruption affects placental function and leads to pregnancy loss/recurrent miscarriage (RM); 3) and if pathogenic variants are associated with isolated fetal growth restriction (FGR). Methods Published data were analyzed, particularly reviewing position/type of variant, pregnancy, growth data, and associated endocrine features. Genetic analysis of SAMD9 was performed in products of conception (POC, n=26), RM couples, (couples n=48; individuals n=96), children with FGR (n=44), SGA (n=20), and clinical Silver-Russell Syndrome (SRS, n=8), (total n=194). Results To date, SAMD9 variants are reported in 116 individuals [MDS/monosomy 7, 64 (55.2\%); MIRAGE, 52 (44.8\%)]. Children with MIRAGE features are increasingly reported without an adrenal phenotype (11/52, 21.2\%). Infants without adrenal dysfunction were heavier at birth (median 1515~g versus 1020~g; P \< 0.05) and born later (median 34.5 weeks versus 31.0; P \< 0.05) compared to those with adrenal insufficiency. In MIRAGE patients, hypospadias is a common feature. Additional endocrinopathies include hypothyroidism, hypo- and hyper-glycemia, short stature and panhypopituitarism. Despite this increasing range of phenotypes, genetic analysis did not reveal any likely pathogenic variants/enrichment of specific variants in SAMD9 in the pregnancy loss/growth restriction cohorts studied. Conclusion MIRAGE syndrome is more phenotypically diverse than originally reported and includes growth restriction and multisystem features, but without adrenal insufficiency. Endocrinopathies might be overlooked or develop gradually, and may be underreported. As clinical features including FGR, severe infections, anemia and lung problems can be non-specific and are often seen in neonatal medicine, SAMD9-associated conditions may be underdiagnosed. Reaching a specific diagnosis of MIRAGE syndrome is critical for personalized management.}, pmcid = {PMC9433874}, pmid = {36060959}, file = {C:\Users\adama\Zotero\storage\4UXVPVN8\Suntharalingham et al. - 2022 - Emerging phenotypes linked to variants in SAMD9 and MIRAGE syndrome.pdf} } @article{tanwattanaHumanBST2Inhibits2023, title = {Human {{BST2}} Inhibits Rabies Virus Release Independently of Cysteine-Linked Dimerization and Asparagine-Linked Glycosylation}, author = {Tanwattana, Nathiphat and Wanasen, Nanchaya and Jantraphakorn, Yuparat and Srisutthisamphan, Kanjana and Chailungkarn, Thanathom and Boonrungsiman, Suwimon and Lumlertdacha, Boonlert and Lekchareonsuk, Porntippa and Kaewborisuth, Challika}, editor = {Yasuda, Jiro}, year = 2023, month = nov, journal = {PLOS ONE}, volume = {18}, number = {11}, pages = {e0292833}, issn = {1932-6203}, doi = {10.1371/journal.pone.0292833}, urldate = {2026-08-18}, abstract = {The innate immune response is a first-line defense mechanism triggered by rabies virus (RABV). Interferon (IFN) signaling and ISG products have been shown to confer resistance to RABV at various stages of the virus's life cycle. Human tetherin, also known as bone marrow stromal cell antigen 2 (hBST2), is a multifunctional transmembrane glycoprotein induced by IFN that has been shown to effectively counteract many viruses through diverse mechanisms. Here, we demonstrate that hBST2 inhibits RABV budding by tethering new virions to the cell surface. It was observed that release of virus-like particles (VLPs) formed by RABV G (RABV-G VLPs), but not RABV M (RABV-G VLPs), were suppressed by hBST2, indicating that RABV-G has a specific effect on the hBST2-mediated restriction of RABV. The ability of hBST2 to prevent the release of RABV-G VLPs and impede RABV growth kinetics is retained even when hBST2 has mutations at dimerization and/or glycosylation sites, making hBST2 an antagonist to RABV, with multiple mechanisms possibly contributing to the hBST2-mediated suppression of RABV. Our findings expand the knowledge of host antiviral mechanisms that control RABV infection.}, langid = {english}, pmcid = {PMC10624315}, pmid = {37922253}, file = {C:\Users\adama\Zotero\storage\FZLZPC8Q\Tanwattana et al. - 2023 - Human BST2 inhibits rabies virus release independently of cysteine-linked dimerization and asparagin.pdf} } @article{turanNuclearMxAProteins2004, title = {Nuclear {{MxA}} Proteins Form a Complex with Influenza Virus {{NP}} and Inhibit the Transcription of the Engineered Influenza Virus Genome}, author = {Turan, K.}, year = 2004, month = jan, journal = {Nucleic Acids Research}, volume = {32}, number = {2}, pages = {643--652}, issn = {1362-4962}, doi = {10.1093/nar/gkh192}, urldate = {2026-08-18}, langid = {english}, pmcid = {PMC373319}, pmid = {14752052} } @article{valdezSchlafen11Restricts2019, title = {Schlafen 11 {{Restricts Flavivirus Replication}}}, author = {Valdez, Federico and Salvador, Julienne and Palermo, Pedro M. and Mohl, Jonathon E. and Hanley, Kathryn A. and Watts, Douglas and Llano, Manuel}, editor = {Heise, Mark T.}, year = 2019, month = aug, journal = {Journal of Virology}, volume = {93}, number = {15}, pages = {e00104-19}, issn = {0022-538X, 1098-5514}, doi = {10.1128/JVI.00104-19}, urldate = {2026-08-18}, abstract = {We provide evidence that the cellular protein Schlafen 11 (Slfn11) impairs replication of flaviviruses, including West Nile virus (WNV), dengue virus (DENV), and Zika virus (ZIKV). However, replication of single-stranded negative RNA viruses was not affected. Specifically, Slfn11 decreases the infectivity of WNV potentially by preventing virus-induced modifications of the host tRNA repertoire that could lead to enhanced viral protein folding. Furthermore, we demonstrate that Slfn11 is not the limiting factor of this novel broad antiviral pathway. , ABSTRACT Schlafen 11 (Slfn11) is an interferon-stimulated gene that controls the synthesis of proteins by regulating tRNA abundance. Likely through this mechanism, Slfn11 has previously been shown to impair human immunodeficiency virus type 1 (HIV-1) infection and the expression of codon-biased open reading frames. Because replication of positive-sense single-stranded RNA [(+)ssRNA] viruses requires the immediate translation of the incoming viral genome, whereas negative-sense single-stranded RNA [(-)ssRNA] viruses carry at infection an RNA replicase that makes multiple translation-competent copies of the incoming viral genome, we reasoned that (+)ssRNA viruses will be more sensitive to the effect of Slfn11 on protein synthesis than (-)ssRNA viruses. To evaluate this hypothesis, we tested the effects of Slfn11 on the replication of a panel of ssRNA viruses in the human glioblastoma cell line A172, which naturally expresses Slfn11. Depletion of Slfn11 significantly increased the replication of (+)ssRNA viruses from the Flavivirus genus, including West Nile virus (WNV), dengue virus (DENV), and Zika virus (ZIKV), but had no significant effect on the replication of the (-)ssRNA viruses vesicular stomatitis virus (VSV) ( Rhabdoviridae family) and Rift Valley fever virus (RVFV) ( Phenuiviridae family). Quantification of the ratio of genome-containing viral particles to PFU indicated that Slfn11 impairs WNV infectivity. Intriguingly, Slfn11 prevented WNV-induced downregulation of a subset of tRNAs implicated in the translation of 11.8\% of the viral polyprotein. Low-abundance tRNAs might promote optimal protein folding and enhance viral infectivity, as previously reported. In summary, this study demonstrates that Slfn11 restricts flavivirus replication by impairing viral infectivity. IMPORTANCE We provide evidence that the cellular protein Schlafen 11 (Slfn11) impairs replication of flaviviruses, including West Nile virus (WNV), dengue virus (DENV), and Zika virus (ZIKV). However, replication of single-stranded negative RNA viruses was not affected. Specifically, Slfn11 decreases the infectivity of WNV potentially by preventing virus-induced modifications of the host tRNA repertoire that could lead to enhanced viral protein folding. Furthermore, we demonstrate that Slfn11 is not the limiting factor of this novel broad antiviral pathway.}, langid = {english}, pmcid = {PMC6639263}, pmid = {31118262}, file = {C:\Users\adama\Zotero\storage\DQA3UFLZ\Valdez et al. - 2019 - Schlafen 11 Restricts Flavivirus Replication.pdf} } @article{wangGenomewideCRISPRScreenings2024, title = {Genome-Wide {{CRISPR}} Screenings Identified {{SMCHD1}} as a Host-Restricting Factor for {{AAV}} Transduction}, author = {Wang, Chenlu and Liu, Yu and Xiong, Jingfei and Xie, Kun and Wang, Tianshu and Hu, Yu and Fu, Huancheng and Zhang, Baiquan and Huang, Xiaochao and Bao, Hui and Cai, Haoyang and Dong, Biao and Li, Zhonghan}, editor = {Neumann, Donna M.}, year = 2024, month = jul, journal = {PLOS Pathogens}, volume = {20}, number = {7}, pages = {e1012344}, issn = {1553-7374}, doi = {10.1371/journal.ppat.1012344}, urldate = {2026-08-18}, abstract = {AAV-mediated gene therapy typically requires a high dose of viral transduction, risking acute immune responses and patient safety, part of which is due to limited understanding of the host-viral interactions, especially post-transduction viral genome processing. Here, through a genome-wide CRISPR screen, we identified SMCHD1 (Structural Maintenance of Chromosomes Hinge Domain 1), an epigenetic modifier, as a critical broad-spectrum restricting host factor for post-entry AAV transgene expression. SMCHD1 knock-down by RNAi and CRISPRi or knock-out by CRISPR all resulted in significantly enhanced transgene expression across multiple viral serotypes, as well as for both single-strand and self-complementary AAV genome types. Mechanistically, upon viral transduction, SMCHD1 effectively repressed AAV transcription by the formation of an LRIF1-HP1-containing protein complex and directly binding with the AAV genome to maintain a heterochromatin-like state. SMCHD1 -KO or LRIF1 -KD could disrupt such a complex and thus result in AAV transcriptional activation. Together, our results highlight the host factor-induced chromatin remodeling as a critical inhibitory mechanism for AAV transduction and may shed light on further improvement in AAV-based gene therapy.}, langid = {english}, pmcid = {PMC11257396}, pmid = {38976714}, file = {C:\Users\adama\Zotero\storage\WECDVV9J\Wang et al. - 2024 - Genome-wide CRISPR screenings identified SMCHD1 as a host-restricting factor for AAV transduction.pdf} } @article{wangInterferoninducibleMX2Host2020, title = {Interferon-Inducible {{MX2}} Is a Host Restriction Factor of Hepatitis {{B}} Virus Replication}, author = {Wang, Yong-Xiang and Niklasch, Matthias and Liu, Tiantian and Wang, Yang and Shi, Bisheng and Yuan, Wenjie and Baumert, Thomas F. and Yuan, Zhenghong and Tong, Shuping and Nassal, Michael and Wen, Yu-Mei}, year = 2020, month = may, journal = {Journal of Hepatology}, volume = {72}, number = {5}, pages = {865--876}, issn = {01688278}, doi = {10.1016/j.jhep.2019.12.009}, urldate = {2026-08-18}, langid = {english}, pmid = {31863794} } @article{wangRolePSGL1Pathogenesis2019, title = {The Role of {{PSGL-1}} in Pathogenesis of Systemic Inflammatory Response and Coagulopathy in Endotoxemic Mice}, author = {Wang, Xiao-li and Deng, Hua-fei and Tan, Chu-yi and Xiao, Zi-hui and Liu, Mei-dong and Liu, Ke and Zhang, Hua-li and Xiao, Xian-zhong}, year = 2019, month = oct, journal = {Thrombosis Research}, volume = {182}, pages = {56--63}, issn = {00493848}, doi = {10.1016/j.thromres.2019.08.019}, urldate = {2026-08-18}, langid = {english}, pmid = {31450009} } @article{whitworthWilmsTumourResulting2024, title = {Wilms Tumour Resulting from Paternal Transmission of a {{TRIM28}} Pathogenic Variant---{{A}} First Report}, author = {Whitworth, James and Armstrong, Ruth and Maher, Eamonn R.}, year = 2024, month = mar, journal = {European Journal of Human Genetics}, volume = {32}, number = {3}, pages = {361--364}, issn = {1018-4813, 1476-5438}, doi = {10.1038/s41431-024-01545-7}, urldate = {2026-08-18}, abstract = {Abstract Wilms tumour (nephroblastoma) is a renal embryonal tumour that is frequently caused by constitutional variants in a small range of cancer predisposition genes. TRIM28 has recently been identified as one such gene. Previously, observational data strongly suggested a parent of origin effect, whereby Wilms tumour only occurred following maternal inheritance of a pathogenic genetic variant. However, here we report a child with bilateral Wilms tumour who had inherited a pathogenic TRIM28 variant from their father. This finding suggests that genetic counselling for paternally inherited pathogenic variants in TRIM28 should include discussion of a potential risk of Wilms tumour.}, langid = {english}, pmcid = {PMC10923773}, pmid = {38282073}, file = {C:\Users\adama\Zotero\storage\GIJBACWX\Whitworth et al. - 2024 - Wilms tumour resulting from paternal transmission of a TRIM28 pathogenic variant—A first report.pdf} } @article{wojcikProthromboticFibrinClot2019, title = {Prothrombotic Fibrin Clot Properties Are Associated with Post-Discharge Venous Thromboembolism in Acutely Ill Medical Patients}, author = {W{\'o}jcik, Mariusz and Zar{\k e}ba, Lech and Undas, Anetta}, year = 2019, month = oct, journal = {Thrombosis Research}, volume = {182}, pages = {141--149}, issn = {00493848}, doi = {10.1016/j.thromres.2019.08.010}, urldate = {2026-08-18}, langid = {english}, pmid = {31479942} } @article{wuPhosphoproteomicsRevealsRole2022, title = {Phosphoproteomics {{Reveals}} the {{Role}} of {{Constitutive KAP1 Phosphorylation}} by {{B-cell Receptor Signaling}} in {{Chronic Lymphocytic Leukemia}}}, author = {Wu, Jung-Lin and Wu, Hsin-Yi and Wu, Shang-Ju and Tsai, Ho-Yang and Weng, Shao-Hsing and Lin, Kuen-Tyng and Lin, Liang-In and Yao, Chi-Yuan and Zamanova, Margarita and Lee, Yi-Yuan and Angata, Takashi and Tien, Hwei-Fang and Chen, Yu-Ju and Lin, Kuo-I}, year = 2022, month = aug, journal = {Molecular Cancer Research}, volume = {20}, number = {8}, pages = {1222--1232}, issn = {1541-7786, 1557-3125}, doi = {10.1158/1541-7786.MCR-21-0722}, urldate = {2026-08-18}, abstract = {Abstract Application of B-cell receptor (BCR) pathway inhibitor ibrutinib for chronic lymphocytic leukemia (CLL) is a major breakthrough, yet the downstream effects following inhibition of BCR signaling and during relapse await further clarification. By comparative phosphoproteomic profiling of B cells from patients with CLL and healthy donors, as well as CLL B cells collected at multiple time points during the course of ibrutinib treatment, we provided the landscape of dysregulated phosphoproteome in CLL and its dynamic alterations associated with ibrutinib treatment. Particularly, differential phosphorylation events associated with several signaling pathways, including BCR pathway, were enriched in patient CLL cells. A constitutively elevated phosphorylation level of KAP1 at serine 473 (S473) was found in the majority of CLL samples prior to treatment. Further verification showed that BCR activation promoted KAP1 S473 phosphorylation, whereas ibrutinib treatment abolished it. Depletion of KAP1 in primary CLL cells decelerated cell-cycle progression and ectopic expression of a KAP1 S473 phospho-mimicking mutant accelerated G2--M cell-cycle transition of CLL cells. Moreover, temporal phosphoproteomic profiles using a series of CLL cells isolated from one patient during the ibrutinib treatment revealed the dynamic changes of several molecules associated with BCR signaling in the ibrutinib responsive and recurrent stages. Implications: This phosphoproteomic analysis and functional validation illuminated the phosphorylation of KAP1 at S473 as an important downstream BCR signaling event and a potential indicator for the success of ibrutinib treatment in CLL.}, langid = {english}, pmid = {35533307} } @article{xieMxBImpedesNUP358mediated2020, title = {{{MxB}} Impedes the {{NUP358-mediated HIV-1}} Pre-Integration Complex Nuclear Import and Viral Replication Cooperatively with {{CPSF6}}}, author = {Xie, Linlin and Chen, Lang and Zhong, Chaojie and Yu, Ting and Ju, Zhao and Wang, Meirong and Xiong, Hairong and Zeng, Yan and Wang, Jianhua and Hu, Haitao and Hou, Wei and Feng, Yong}, year = 2020, month = dec, journal = {Retrovirology}, volume = {17}, number = {1}, pages = {16}, issn = {1742-4690}, doi = {10.1186/s12977-020-00524-2}, urldate = {2026-08-18}, abstract = {Abstract Background The human myxovirus resistance 2 (Mx2/MxB) protein was originally found to regulate cytoplasmic-nuclear transport but was recently reported to restrict HIV-1 replication by binding to HIV-1 capsid (CA), preventing uncoating, the nuclear import of pre-integration complex (PIC) and viral DNA integration. This work explores the mechanisms of MxB-mediated HIV-1 inhibition. Results We demonstrated that MxB represses NUP358-mediated PIC nuclear import and HIV-1 replication. Moreover, MxB's effects on PIC nuclear import and HIV-1 replication depend critically on cofactor cleavage and polyadenylation specificity factor subunit 6 (CPSF6). MxB binds nucleoporin NUP358, blocks NUP358-CA interaction, thereby impeding the nuclear import of HIV-1 PIC with CPSF6 binding to PIC. More intriguingly, CPSF6's role in nuclear import depends on MxB, being a facilitator of HIV-1 nuclear import on its own, but becoming an inhibitor when MxB is present. Conclusions Our work establishes that MxB impedes the NUP358-mediated HIV-1 nuclear import and viral replication cooperatively with CPSF6.}, langid = {english}, pmcid = {PMC7322711}, pmid = {32600399}, file = {C:\Users\adama\Zotero\storage\JN8CSSMX\Xie et al. - 2020 - MxB impedes the NUP358-mediated HIV-1 pre-integration complex nuclear import and viral replication c.pdf} } @article{xuIFI16PartnersKAP12022, title = {{{IFI16 Partners}} with {{KAP1}} to {{Maintain Epstein-Barr Virus Latency}}}, author = {Xu, Huanzhou and Li, Xiaofan and Rousseau, Beth A. and Akinyemi, Ibukun A. and Frey, Tiffany R. and Zhou, Kevin and Droske, Lauren E. and Mitchell, Jennifer A. and McIntosh, Michael T. and {Bhaduri-McIntosh}, Sumita}, editor = {Goodrum, Felicia}, year = 2022, month = sep, journal = {Journal of Virology}, volume = {96}, number = {17}, pages = {e01028-22}, issn = {0022-538X, 1098-5514}, doi = {10.1128/jvi.01028-22}, urldate = {2026-08-18}, abstract = {The interferon-gamma inducible protein 16 (IFI16) is a nuclear DNA sensor that mediates antiviral responses by activating the inflammasome, triggering an interferon response, and silencing lytic genes of herpesviruses. The last, which helps maintain latency of the oncoherpesvirus Epstein-Barr virus (EBV), is accomplished via H3K9me3 heterochromatinization through unknown mechanisms. , ABSTRACT Herpesviruses establish latency to ensure permanent residence in their hosts. Upon entry into a cell, these viruses are rapidly silenced by the host, thereby limiting the destructive viral lytic phase while allowing the virus to hide from the immune system. Notably, although the establishment of latency by the oncogenic herpesvirus Epstein-Barr virus (EBV) requires the expression of viral latency genes, latency can be maintained with a negligible expression of viral genes. Indeed, in several herpesviruses, the host DNA sensor IFI16 facilitated latency via H3K9me3 heterochromatinization. This silencing mark is typically imposed by the constitutive heterochromatin machinery (HCM). The HCM, in an antiviral role, also silences the lytic phase of EBV and other herpes viruses. We investigated if IFI16 restricted EBV lytic activation by partnering with the HCM and found that IFI16 interacted with core components of the HCM, including the KRAB-associated protein 1 (KAP1) and the site-specific DNA binding KRAB-ZFP SZF1. This partnership silenced the EBV lytic switch protein ZEBRA, encoded by the BZLF1 gene, thereby favoring viral latency. Indeed, IFI16 contributed to H3K9 trimethylation at lytic genes of all kinetic classes. In defining topology, we found that IFI16 coenriched with KAP1 at the BZLF1 promoter, and while IFI16 and SZF1 were each adjacent to KAP1 in latent cells, IFI16 and SZF1 were not. Importantly, we also found that disruption of latency involved rapid downregulation of IFI16 transcription. These findings revealed a previously unknown partnership between IFI16 and the core HCM that supports EBV latency via antiviral heterochromatic silencing. IMPORTANCE The interferon-gamma inducible protein 16 (IFI16) is a nuclear DNA sensor that mediates antiviral responses by activating the inflammasome, triggering an interferon response, and silencing lytic genes of herpesviruses. The last, which helps maintain latency of the oncoherpesvirus Epstein-Barr virus (EBV), is accomplished via H3K9me3 heterochromatinization through unknown mechanisms. Here, we report that IFI16 physically partners with the core constitutive heterochromatin machinery to silence the key EBV lytic switch protein, thereby ensuring continued viral latency in B lymphocytes. We also find that disruption of latency involves rapid transcriptional downregulation of IFI16. These findings point to hitherto unknown physical and functional partnerships between a well-known antiviral mechanism and the core components of the constitutive heterochromatin machinery.}, langid = {english}, pmcid = {PMC9472614}, pmid = {35969079} } @article{yangKAP1StabilizesMYCN2024, title = {{{KAP1}} Stabilizes {{MYCN mRNA}} and Promotes Neuroblastoma Tumorigenicity by Protecting the {{RNA m6A}} Reader {{YTHDC1}} Protein Degradation}, author = {Yang, Yi and Zhang, Yingwen and Chen, Guoyu and Sun, Bowen and Luo, Fei and Gao, Yijin and Feng, Haizhong and Li, Yanxin}, year = 2024, month = may, journal = {Journal of Experimental \& Clinical Cancer Research}, volume = {43}, number = {1}, pages = {141}, issn = {1756-9966}, doi = {10.1186/s13046-024-03040-9}, urldate = {2026-08-18}, abstract = {Neuroblastoma (NB) patients with amplified MYCN often face a grim prognosis and are resistant to existing therapies, yet MYCN protein is considered undruggable. KAP1 (also named TRIM28) plays a crucial role in multiple biological activities. This study aimed to investigate the relationship between KAP1 and MYCN in NB.}, langid = {english}, pmcid = {PMC11092262}, pmid = {38745192}, keywords = {KAP1,m6A,METTL3,mRNA stability,MYCN,Neuroblastoma,YTHDC1}, file = {C:\Users\adama\Zotero\storage\PEIX5HCC\Yang et al. - 2024 - KAP1 stabilizes MYCN mRNA and promotes neuroblastoma tumorigenicity by protecting the RNA m6A reader.pdf} } @article{yuIFITMProteinsRestrict2015, title = {{{IFITM Proteins Restrict HIV-1 Infection}} by {{Antagonizing}} the {{Envelope Glycoprotein}}}, author = {Yu, Jingyou and Li, Minghua and Wilkins, Jordan and Ding, Shilei and Swartz, Talia~H. and Esposito, Anthony~M. and Zheng, Yi-Min and Freed, Eric~O. and Liang, Chen and Chen, Benjamin~K. and Liu, Shan-Lu}, year = 2015, month = oct, journal = {Cell Reports}, volume = {13}, number = {1}, pages = {145--156}, issn = {22111247}, doi = {10.1016/j.celrep.2015.08.055}, urldate = {2026-08-18}, langid = {english}, pmcid = {PMC4602366}, pmid = {26387945}, file = {C:\Users\adama\Zotero\storage\AC9HE72Q\Yu et al. - 2015 - IFITM Proteins Restrict HIV-1 Infection by Antagonizing the Envelope Glycoprotein.pdf} }