{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T03:03:32Z","timestamp":1787022212656,"version":"build-2736575974"},"update-to":[{"DOI":"10.1371\/journal.ppat.1012702","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2024,12,12]],"date-time":"2024-12-12T00:00:00Z","timestamp":1733961600000}}],"reference-count":69,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2024,12,2]],"date-time":"2024-12-02T00:00:00Z","timestamp":1733097600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Health and Medical Research Council of Australia","award":["APP1184867"],"award-info":[{"award-number":["APP1184867"]}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["GRK 1871\/2"],"award-info":[{"award-number":["GRK 1871\/2"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Victorian Government\u2019s Operational Infrastructure Support Programme"},{"DOI":"10.13039\/501100015971","name":"Hudson Institute of Medical Research","doi-asserted-by":"publisher","award":["Innovation Seed Grant"],"award-info":[{"award-number":["Innovation Seed Grant"]}],"id":[{"id":"10.13039\/501100015971","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>The testis is a reservoir for viruses that can cause persistent infection and adversely affect male reproductive health, an observation commonly attributed to deficiencies in inducible antiviral defence mechanisms. In this study, we demonstrate that interferon-epsilon (IFN\u03b5), a type I interferon initially discovered in female reproductive epithelia, is constitutively expressed by meiotic and post-meiotic spermatogenic cells, Leydig cells and macrophages in mouse testes. A similar distribution pattern was observed in human testes. Mice lacking IFN\u025b were more susceptible to Zika virus-induced inflammation and damage of the testis and epididymis compared to wild-type mice. Exogenous IFN\u03b5 treatment reduced the viral infection burden in cultured human testicular cells by inducing interferon-stimulated gene expression, and reducing inflammatory gene expression and cell damage. Treatment was more effective when administered prior to infection. These data indicate a critical role for constitutively-expressed IFN\u025b in limiting viral infection and inflammatory damage in the male reproductive tract.<\/jats:p>","DOI":"10.1371\/journal.ppat.1012702","type":"journal-article","created":{"date-parts":[[2024,12,2]],"date-time":"2024-12-02T14:05:13Z","timestamp":1733148313000},"page":"e1012702","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":16,"title":["Interferon epsilon is produced in the testis and protects the male reproductive tract against virus infection, inflammation and damage"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5584-1371","authenticated-orcid":true,"given":"Rukmali","family":"Wijayarathna","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eveline D.","family":"de Geus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosemary","family":"Genovese","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linden J.","family":"Gearing","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgie","family":"Wray-McCann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajini","family":"Sreenivasan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiba","family":"Hasan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monika","family":"Fijak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Stanton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Fietz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian","family":"Pilatz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans-Christian","family":"Schuppe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle D.","family":"Tate","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul J.","family":"Hertzog","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark P.","family":"Hedger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,12,2]]},"reference":[{"key":"ppat.1012702.ref001","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.1152\/physrev.00021.2019","article-title":"From Ancient to Emerging Infections: The Odyssey of Viruses in the Male Genital Tract","volume":"100","author":"A Le Tortorec","year":"2020","journal-title":"Physiological reviews"},{"key":"ppat.1012702.ref002","doi-asserted-by":"crossref","first-page":"e1008601","DOI":"10.1371\/journal.ppat.1008601","article-title":"Zika virus tropism during early infection of the testicular interstitium and its role in viral pathogenesis in the testes.","volume":"16","author":"KA Tsetsarkin","year":"2020","journal-title":"PLOS Pathogens"},{"key":"ppat.1012702.ref003","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1038\/nature20556","article-title":"Zika virus infection damages the testes in mice","volume":"540","author":"J Govero","year":"2016","journal-title":"Nature"},{"key":"ppat.1012702.ref004","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1111\/andr.13073","article-title":"Testicular pathology in fatal COVID-19: A descriptive autopsy study.","volume":"10","author":"AN Duarte-Neto","year":"2022","journal-title":"Andrology"},{"key":"ppat.1012702.ref005","doi-asserted-by":"crossref","first-page":"e28970","DOI":"10.1002\/jmv.28970","article-title":"Acute orchitis deciphered: Coxsackievirus B strains are the main etiology and their presence in semen is associated with acute inflammation and risk of persistent oligozoospermia","volume":"95","author":"A Pilatz","year":"2023","journal-title":"J Med Virol"},{"key":"ppat.1012702.ref006","doi-asserted-by":"crossref","first-page":"625","DOI":"10.2164\/jandrol.111.012989","article-title":"Immunophysiology and Pathology of Inflammation in the Testis and Epididymis","volume":"32","author":"MP Hedger","year":"2011","journal-title":"Journal of Andrology"},{"key":"ppat.1012702.ref007","doi-asserted-by":"crossref","first-page":"913502","DOI":"10.3389\/fimmu.2022.913502","article-title":"Sertoli Cell Immune Regulation: A Double-Edged Sword.","volume":"13","author":"RL Washburn","year":"2022","journal-title":"Front Immunol"},{"key":"ppat.1012702.ref008","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1095\/biolreprod.110.089425","article-title":"Immunoprotective properties of primary Sertoli cells in mice: potential functional pathways that confer immune privilege","volume":"86","author":"TJ Doyle","year":"2012","journal-title":"Biol Reprod"},{"key":"ppat.1012702.ref009","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.mce.2010.03.022","article-title":"Immunological, paracrine and endocrine aspects of testicular immune privilege","volume":"335","author":"A Meinhardt","year":"2011","journal-title":"Molecular and Cellular Endocrinology"},{"key":"ppat.1012702.ref010","doi-asserted-by":"crossref","first-page":"909341","DOI":"10.3389\/fimmu.2022.909341","article-title":"Human Testicular Germ Cells, a Reservoir for Zika Virus, Lack Antiviral Response Upon Zika or Poly(I:C) Exposure.","volume":"13","author":"ON Kuassivi","year":"2022","journal-title":"Front Immunol"},{"key":"ppat.1012702.ref011","doi-asserted-by":"crossref","first-page":"3081","DOI":"10.1210\/endo.139.7.6083","article-title":"Expression of interferons-alpha and -gamma in testicular interstitial tissue and spermatogonia of the rat","volume":"139","author":"N Dejucq","year":"1998","journal-title":"Endocrinology"},{"key":"ppat.1012702.ref012","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/S0165-0378(98)00065-5","article-title":"Interferons and interferon-induced antiviral proteins in the testis","volume":"41","author":"N Dejucq","year":"1998","journal-title":"J Reprod Immunol"},{"key":"ppat.1012702.ref013","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1016\/S1473-3099(16)30330-9","article-title":"Rollin PE Zika virus in semen: lessons from Ebola","volume":"16","author":"LJ Purpura","year":"2016","journal-title":"The Lancet Infectious Diseases"},{"key":"ppat.1012702.ref014","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1016\/j.chom.2018.08.003","article-title":"Persistent Marburg Virus Infection in the Testes of Nonhuman Primate Survivors","volume":"24","author":"KM Coffin","year":"2018","journal-title":"Cell host & microbe"},{"key":"ppat.1012702.ref015","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1128\/MMBR.65.2.208-231.2001","article-title":"Viruses in the Mammalian Male Genital Tract and Their Effects on the Reproductive System","volume":"65","author":"N Dejucq","year":"2001","journal-title":"Microbiology and Molecular Biology Reviews"},{"key":"ppat.1012702.ref016","doi-asserted-by":"crossref","first-page":"335","DOI":"10.4103\/aja.aja_82_20","article-title":"Viral infections and implications for male reproductive health","volume":"23","author":"TA Teixeira","year":"2021","journal-title":"Asian journal of andrology"},{"key":"ppat.1012702.ref017","doi-asserted-by":"crossref","first-page":"e1010843","DOI":"10.1371\/journal.ppat.1010843","article-title":"Constitutive expression and distinct properties of IFN-epsilon protect the female reproductive tract from Zika virus infection.","volume":"19","author":"RC Coldbeck-Shackley","year":"2023","journal-title":"PLoS Pathog"},{"key":"ppat.1012702.ref018","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1126\/science.1233321","article-title":"Interferon-\u03b5 protects the female reproductive tract from viral and bacterial infection","volume":"339","author":"KY Fung","year":"2013","journal-title":"Science"},{"key":"ppat.1012702.ref019","doi-asserted-by":"crossref","first-page":"101328","DOI":"10.1016\/j.smim.2019.101328","article-title":"Properties and functions of the novel type I Interferon Epsilon","volume":"43","author":"ZRC Marks","year":"2019","journal-title":"Seminars in immunology"},{"key":"ppat.1012702.ref020","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1038\/s41586-023-06421-w","article-title":"Interferon-\u03b5 is a tumour suppressor and restricts ovarian cancer","volume":"620","author":"ZRC Marks","year":"2023","journal-title":"Nature"},{"key":"ppat.1012702.ref021","doi-asserted-by":"crossref","first-page":"e71320","DOI":"10.1371\/journal.pone.0071320","article-title":"IFN-\u03b5 is constitutively expressed by cells of the reproductive tract and is inefficiently secreted by fibroblasts and cell lines","volume":"8","author":"P Hermant","year":"2013","journal-title":"PLoS One"},{"key":"ppat.1012702.ref022","doi-asserted-by":"crossref","first-page":"2195","DOI":"10.1056\/NEJMc1604449","article-title":"Evidence of Sexual Transmission of Zika Virus","volume":"374","author":"E D\u2019Ortenzio","year":"2016","journal-title":"The New England journal of medicine"},{"key":"ppat.1012702.ref023","doi-asserted-by":"crossref","first-page":"4510","DOI":"10.1038\/s41598-018-22840-6","article-title":"Sexual transmission of Zika virus enhances in utero transmission in a mouse model.","volume":"8","author":"NK Duggal","year":"2018","journal-title":"Sci Rep"},{"key":"ppat.1012702.ref024","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1093\/humupd\/dmx024","article-title":"Zika virus and reproduction: facts, questions and current management","volume":"23","author":"S Epelboin","year":"2017","journal-title":"Hum Reprod Update"},{"key":"ppat.1012702.ref025","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1007\/978-3-031-31574-9_11","volume-title":"In Andrology: Male Reproductive Health and Dysfunction","author":"D Fietz","year":"2023"},{"key":"ppat.1012702.ref026","doi-asserted-by":"crossref","first-page":"e0290846","DOI":"10.1371\/journal.pone.0290846","article-title":"Sertoli cell-enriched proteins in mouse and human testicular interstitial fluid","volume":"18","author":"L O\u2019Donnell","year":"2023","journal-title":"PLoS One"},{"key":"ppat.1012702.ref027","volume-title":"WHO laboratory manual for the examination and processing of human semen","author":"World Health Organization","year":"2010","edition":"5"},{"key":"ppat.1012702.ref028","volume-title":"WHO laboratory manual for the examination and processing of human semen","author":"World Health Organization","year":"2021","edition":"6"},{"key":"ppat.1012702.ref029","doi-asserted-by":"crossref","DOI":"10.1093\/humrep\/deae107","article-title":"Monocytes expressing activin A and CCR2 exacerbate chronic testicular inflammation by promoting immune cell infiltration","author":"H Hasan","year":"2024","journal-title":"Human reproduction (Oxford, England)."},{"key":"ppat.1012702.ref030","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.jri.2006.01.002","article-title":"The relationship between immunosuppressive activity and immunoregulatory cytokines in seminal plasma: influence of sperm autoimmunity and seminal leukocytes","volume":"71","author":"R Ochsenk\u00fchn","year":"2006","journal-title":"J Reprod Immunol"},{"key":"ppat.1012702.ref031","doi-asserted-by":"crossref","first-page":"1824","DOI":"10.1210\/endo-121-5-1824","article-title":"The Heterogeneity of Isolated Adult Rat Leydig Cells Separated on Percoll Density Gradients: An Immunological, Cytochemical, and Functional Analysis","volume":"121","author":"MP Hedger","year":"1987","journal-title":"Endocrinology"},{"key":"ppat.1012702.ref032","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/S0303-7207(98)00190-7","article-title":"A rapid method of Sertoli cell isolation by DSA lectin, allowing mitotic analyses","volume":"146","author":"S Scarpino","year":"1998","journal-title":"Molecular and Cellular Endocrinology"},{"key":"ppat.1012702.ref033","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.mce.2009.02.007","article-title":"Regulation of interleukin 1\u03b1, activin and inhibin by lipopolysaccharide in Sertoli cells from prepubertal rats","volume":"307","author":"WR Winnall","year":"2009","journal-title":"Molecular and Cellular Endocrinology"},{"key":"ppat.1012702.ref034","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1677\/joe.1.06634","article-title":"FSH regulates the formation of adherens junctions and ectoplasmic specialisations between rat Sertoli cells in vitro and in vivo","volume":"189","author":"Sluka P","year":"2006","journal-title":"Journal of Endocrinology"},{"key":"ppat.1012702.ref035","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1002\/mrd.1080360406","article-title":"Identification of receptor tyrosine kinases in the rat testis","volume":"36","author":"KL Loveland","year":"1993","journal-title":"Molecular reproduction and development"},{"key":"ppat.1012702.ref036","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1016\/j.chom.2016.03.010","article-title":"A Mouse Model of Zika Virus Pathogenesis","volume":"19","author":"HM Lazear","year":"2016","journal-title":"Cell host & microbe"},{"key":"ppat.1012702.ref037","doi-asserted-by":"crossref","DOI":"10.3390\/v14020377","article-title":"Zika Virus Infection of Sertoli Cells Alters Protein Expression Involved in Activated Immune and Antiviral Response Pathways, Carbohydrate Metabolism and Cardiovascular Disease.","volume":"14","author":"MU Rashid","year":"2022","journal-title":"Viruses"},{"key":"ppat.1012702.ref038","doi-asserted-by":"crossref","first-page":"e0008335","DOI":"10.1371\/journal.pntd.0008335","article-title":"Zika virus dysregulates human Sertoli cell proteins involved in spermatogenesis with little effect on tight junctions","volume":"14","author":"MU Rashid","year":"2020","journal-title":"PLoS neglected tropical diseases"},{"key":"ppat.1012702.ref039","doi-asserted-by":"crossref","first-page":"eabm0972","DOI":"10.1126\/sciadv.abm0972","article-title":"Origin, specification and differentiation of a rare supporting-like lineage in the developing mouse gonad","volume":"8","author":"C May\u00e8re","year":"2022","journal-title":"Science advances"},{"key":"ppat.1012702.ref040","doi-asserted-by":"crossref","first-page":"5477","DOI":"10.1038\/s41598-018-23899-x","article-title":"Human Sertoli cells support high levels of Zika virus replication and persistence.","volume":"8","author":"A Kumar","year":"2018","journal-title":"Sci Rep"},{"key":"ppat.1012702.ref041","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1002\/gcc.20520","article-title":"Further characterization of the first seminoma cell line TCam-2","volume":"47","author":"J de Jong","year":"2008","journal-title":"Genes, Chromosomes and Cancer"},{"key":"ppat.1012702.ref042","doi-asserted-by":"crossref","first-page":"e204","DOI":"10.1111\/j.1365-2605.2011.01170.x","article-title":"TCam-2 seminoma cell line exhibits characteristic foetal germ cell responses to TGF-beta ligands and retinoic acid","volume":"34","author":"JC Young","year":"2011","journal-title":"Int J Androl"},{"key":"ppat.1012702.ref043","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1111\/andr.12365","article-title":"An in vitro model demonstrates the potential of neoplastic human germ cells to influence the tumour microenvironment.","volume":"5","author":"B Klein","year":"2017","journal-title":"Andrology"},{"key":"ppat.1012702.ref044","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1038\/icb.2016.123","article-title":"Interferon epsilon promotes HIV restriction at multiple steps of viral replication","volume":"95","author":"A Garcia-Minambres","year":"2017","journal-title":"Immunol Cell Biol"},{"key":"ppat.1012702.ref045","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.jcmgh.2023.10.006","article-title":"Epithelially Restricted Interferon Epsilon Protects Against Colitis.","volume":"17","author":"ED de Geus","year":"2023","journal-title":"Cellular and molecular gastroenterology and hepatology"},{"key":"ppat.1012702.ref046","doi-asserted-by":"crossref","first-page":"42391","DOI":"10.1038\/srep42391","article-title":"Testicular activin and follistatin levels are elevated during the course of experimental autoimmune epididymo-orchitis in mice.","volume":"7","author":"N Nicolas","year":"2017","journal-title":"Sci Rep"},{"key":"ppat.1012702.ref047","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1007\/s00441-020-03215-8","article-title":"Region-specific immune responses to autoimmune epididymitis in the murine reproductive tract","volume":"381","author":"R Wijayarathna","year":"2020","journal-title":"Cell Tissue Res"},{"key":"ppat.1012702.ref048","article-title":"New aspects of activin biology in epididymal function and immunopathology","author":"R Wijayarathna","year":"2023","journal-title":"Andrology"},{"key":"ppat.1012702.ref049","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1677\/joe.0.1480267","article-title":"Development and application of a two-site enzyme immunoassay for the determination of \u2019total\u2019 activin-A concentrations in serum and follicular fluid.","volume":"148","author":"PG Knight","year":"1996","journal-title":"Journal of Endocrinology"},{"key":"ppat.1012702.ref050","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method.","volume":"25","author":"KJ Livak","year":"2001","journal-title":"Methods (San Diego, Calif.)"},{"key":"ppat.1012702.ref051","volume-title":"R: A language and environment for statistical computing","author":"Team RC","year":"2021"},{"key":"ppat.1012702.ref052","doi-asserted-by":"crossref","first-page":"e1006361","DOI":"10.1371\/journal.pcbi.1006361","article-title":"scPipe: A flexible R\/Bioconductor preprocessing pipeline for single-cell RNA-sequencing data","volume":"14","author":"L Tian","year":"2018","journal-title":"PLOS Computational Biology"},{"key":"ppat.1012702.ref053","doi-asserted-by":"crossref","first-page":"e47","DOI":"10.1093\/nar\/gkz114","article-title":"The R package Rsubread is easier, faster, cheaper and better for alignment and quantification of RNA sequencing reads","volume":"47","author":"Y Liao","year":"2019","journal-title":"Nucleic acids research"},{"key":"ppat.1012702.ref054","doi-asserted-by":"crossref","first-page":"3439","DOI":"10.1093\/bioinformatics\/bti525","article-title":"BioMart and Bioconductor: a powerful link between biological databases and microarray data analysis","volume":"21","author":"S Durinck","year":"2005","journal-title":"Bioinformatics"},{"key":"ppat.1012702.ref055","doi-asserted-by":"crossref","first-page":"1184","DOI":"10.1038\/nprot.2009.97","article-title":"Mapping identifiers for the integration of genomic datasets with the R\/Bioconductor package biomaRt","volume":"4","author":"S Durinck","year":"2009","journal-title":"Nature protocols"},{"key":"ppat.1012702.ref056","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1093\/bioinformatics\/btp616","article-title":"edgeR: a Bioconductor package for differential expression analysis of digital gene expression data","volume":"26","author":"MD Robinson","year":"2010","journal-title":"Bioinformatics"},{"key":"ppat.1012702.ref057","doi-asserted-by":"crossref","first-page":"R25","DOI":"10.1186\/gb-2010-11-3-r25","article-title":"A scaling normalization method for differential expression analysis of RNA-seq data","volume":"11","author":"MD Robinson","year":"2010","journal-title":"Genome Biology"},{"key":"ppat.1012702.ref058","doi-asserted-by":"crossref","first-page":"R29","DOI":"10.1186\/gb-2014-15-2-r29","article-title":"voom: precision weights unlock linear model analysis tools for RNA-seq read counts","volume":"15","author":"CW Law","year":"2014","journal-title":"Genome Biology"},{"key":"ppat.1012702.ref059","doi-asserted-by":"crossref","first-page":"e47","DOI":"10.1093\/nar\/gkv007","article-title":"limma powers differential expression analyses for RNA-sequencing and microarray studies","volume":"43","author":"ME Ritchie","year":"2015","journal-title":"Nucleic acids research"},{"key":"ppat.1012702.ref060","doi-asserted-by":"crossref","first-page":"946","DOI":"10.1214\/16-AOAS920","article-title":"Robust hyperparameter estimation protects against hypervariable genes and improves power to detect differential expression.","volume":"10","author":"B Phipson","year":"2016","journal-title":"The annals of applied statistics"},{"key":"ppat.1012702.ref061","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1093\/bioinformatics\/btp053","article-title":"Testing significance relative to a fold-change threshold is a TREAT","volume":"25","author":"DJ McCarthy","year":"2009","journal-title":"Bioinformatics"},{"key":"ppat.1012702.ref062","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/j.cels.2015.12.004","article-title":"The Molecular Signatures Database (MSigDB) hallmark gene set collection.","volume":"1","author":"A Liberzon","year":"2015","journal-title":"Cell systems"},{"key":"ppat.1012702.ref063","doi-asserted-by":"crossref","first-page":"D672","DOI":"10.1093\/nar\/gkad1025","article-title":"The Reactome Pathway Knowledgebase 2024","volume":"52","author":"M Milacic","year":"2023","journal-title":"Nucleic acids research"},{"key":"ppat.1012702.ref064","doi-asserted-by":"crossref","first-page":"15545","DOI":"10.1073\/pnas.0506580102","article-title":"Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles","volume":"102","author":"A Subramanian","year":"2005","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ppat.1012702.ref065","doi-asserted-by":"crossref","first-page":"e133","DOI":"10.1093\/nar\/gks461","article-title":"Camera: a competitive gene set test accounting for inter-gene correlation","volume":"40","author":"D Wu","year":"2012","journal-title":"Nucleic acids research"},{"key":"ppat.1012702.ref066","doi-asserted-by":"crossref","first-page":"1511","DOI":"10.1016\/j.cell.2016.11.016","article-title":"Zika Virus Causes Testis Damage and Leads to Male Infertility in Mice","volume":"167","author":"W Ma","year":"2016","journal-title":"Cell"},{"key":"ppat.1012702.ref067","doi-asserted-by":"crossref","first-page":"e3146","DOI":"10.1038\/cddis.2017.560","article-title":"Han, D. C-X-C motif chemokine ligand 10 produced by mouse Sertoli cells in response to mumps virus infection induces male germ cell apoptosis","volume":"8","author":"Q Jiang","year":"2017","journal-title":"Cell Death Dis"},{"key":"ppat.1012702.ref068","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.1093\/humrep\/dez073","article-title":"Dexamethasone improves therapeutic outcomes in a preclinical bacterial epididymitis mouse model","volume":"34","author":"B Klein","year":"2019","journal-title":"Human reproduction (Oxford, England)"},{"key":"ppat.1012702.ref069","doi-asserted-by":"crossref","first-page":"472","DOI":"10.4103\/aja.aja_116_19","article-title":"Damaged male germ cells induce epididymitis in mice","volume":"22","author":"WH Liu","year":"2020","journal-title":"Asian journal of andrology"}],"updated-by":[{"DOI":"10.1371\/journal.ppat.1012702","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2024,12,12]],"date-time":"2024-12-12T00:00:00Z","timestamp":1733961600000}}],"container-title":["PLOS Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1012702","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,12]],"date-time":"2024-12-12T13:56:53Z","timestamp":1734011813000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1012702"}},"subtitle":[],"editor":[{"given":"Christopher F.","family":"Basler","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2024,12,2]]},"references-count":69,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2024,12,2]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.ppat.1012702","relation":{},"ISSN":["1553-7374"],"issn-type":[{"value":"1553-7374","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,2]]}}}