{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T22:28:29Z","timestamp":1792621709272,"version":"4.5.0"},"reference-count":98,"publisher":"Rockefeller University Press","issue":"10","license":[{"start":{"date-parts":[[2021,8,16]],"date-time":"2021-08-16T00:00:00Z","timestamp":1629072000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.rupress.org\/terms\/"},{"start":{"date-parts":[[2022,4,4]],"date-time":"2022-04-04T00:00:00Z","timestamp":1649030400000},"content-version":"vor","delay-in-days":231,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Swiss National Science Foundation","doi-asserted-by":"crossref","award":["310030_173132"],"award-info":[{"award-number":["310030_173132"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001711","name":"Swiss National Science Foundation","doi-asserted-by":"crossref","award":["310030B_201271"],"award-info":[{"award-number":["310030B_201271"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001711","name":"Swiss National Science Foundation","doi-asserted-by":"crossref","award":["310030_185321"],"award-info":[{"award-number":["310030_185321"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000781","name":"European Research Council","doi-asserted-by":"publisher","award":["865026"],"award-info":[{"award-number":["865026"]}],"id":[{"id":"10.13039\/501100000781","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,10,4]]},"abstract":"<jats:p>Several RNA viruses can establish life-long persistent infection in mammalian hosts, but the fate of individual virus-infected cells remains undefined. Here we used Cre recombinase\u2013encoding lymphocytic choriomeningitis virus to establish persistent infection in fluorescent cell fate reporter mice. Virus-infected hepatocytes underwent spontaneous noncytolytic viral clearance independently of type I or type II interferon signaling or adaptive immunity. Viral clearance was accompanied by persistent transcriptomic footprints related to proliferation and extracellular matrix remodeling, immune responses, and metabolism. Substantial overlap with persistent epigenetic alterations in HCV-cured patients suggested a universal RNA virus-induced transcriptomic footprint. Cell-intrinsic clearance occurred in cell culture, too, with sequential infection, reinfection cycles separated by a period of relative refractoriness to infection. Our study reveals that systemic persistence of a prototypic noncytolytic RNA virus depends on continuous spread and reinfection. Yet undefined cell-intrinsic mechanisms prevent viral persistence at the single-cell level but give way to profound transcriptomic alterations in virus-cleared cells.<\/jats:p>","DOI":"10.1084\/jem.20210408","type":"journal-article","created":{"date-parts":[[2021,8,16]],"date-time":"2021-08-16T13:36:22Z","timestamp":1629120982000},"update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":12,"title":["Persistent RNA virus infection is short-lived at the single-cell level but leaves transcriptomic footprints"],"prefix":"10.1084","volume":"218","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5198-8165","authenticated-orcid":true,"given":"Peter","family":"Reuther","sequence":"first","affiliation":[{"name":"Department of Biomedicine, Division of Experimental Virology, University of Basel, Basel, Switzerland 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8958-5492","authenticated-orcid":true,"given":"Katrin","family":"Martin","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Division of Experimental Virology, University of Basel, Basel, Switzerland 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0335-2733","authenticated-orcid":true,"given":"Mario","family":"Kreutzfeldt","sequence":"additional","affiliation":[{"name":"Department of Pathology and Immunology, Division of Clinical Pathology, Geneva Faculty of Medicine, Geneva University and University Hospital, Geneva, Switzerland 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1296-5606","authenticated-orcid":true,"given":"Matias","family":"Ciancaglini","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Division of Experimental Virology, University of Basel, Basel, Switzerland 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9076-9264","authenticated-orcid":true,"given":"Florian","family":"Geier","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Bioinformatics Core Facility, University Hospital Basel, Basel, Switzerland 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0259-8611","authenticated-orcid":true,"given":"Diego","family":"Calabrese","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Histology Core Facility, University Hospital Basel, Basel, Switzerland 4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0247-2007","authenticated-orcid":true,"given":"Doron","family":"Merkler","sequence":"additional","affiliation":[{"name":"Department of Pathology and Immunology, Division of Clinical Pathology, Geneva Faculty of Medicine, Geneva University and University Hospital, Geneva, Switzerland 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1594-3189","authenticated-orcid":true,"given":"Daniel D.","family":"Pinschewer","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Division of Experimental Virology, University of Basel, Basel, Switzerland 1"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2021,8,16]]},"reference":[{"key":"2023072804453187400_bib1","doi-asserted-by":"publisher","first-page":"3920","DOI":"10.1128\/jvi.61.12.3920-3929.1987","article-title":"Immune therapy of a persistent and disseminated viral infection","volume":"61","author":"Ahmed","year":"1987","journal-title":"J. Virol."},{"key":"2023072804453187400_bib2","doi-asserted-by":"publisher","first-page":"542","DOI":"10.1136\/gutjnl-2016-312162","article-title":"Proliferation of primary human hepatocytes and prevention of hepatitis B virus reinfection efficiently deplete nuclear cccDNA in vivo","volume":"67","author":"Allweiss","year":"2018","journal-title":"Gut."},{"key":"2023072804453187400_bib3","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1016\/0166-0934(91)90018-U","article-title":"Quantification of lymphocytic choriomeningitis virus with an immunological focus assay in 24- or 96-well plates","volume":"33","author":"Battegay","year":"1991","journal-title":"J. Virol. Methods."},{"key":"2023072804453187400_bib4","doi-asserted-by":"publisher","first-page":"592","DOI":"10.1099\/vir.0.82428-0","article-title":"Contributions of the lymphocytic choriomeningitis virus glycoprotein and polymerase to strain-specific differences in murine liver pathogenicity","volume":"88","author":"Bergthaler","year":"2007","journal-title":"J. Gen. Virol."},{"key":"2023072804453187400_bib5","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.1000080","article-title":"Impaired antibody response causes persistence of prototypic T cell-contained virus","volume":"7","author":"Bergthaler","year":"2009","journal-title":"PLoS Biol."},{"key":"2023072804453187400_bib6","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1126\/science.1059742","article-title":"Interferon-\u03b3-mediated site-specific clearance of alphavirus from CNS neurons","volume":"293","author":"Binder","year":"2001","journal-title":"Science."},{"key":"2023072804453187400_bib7","doi-asserted-by":"publisher","first-page":"490","DOI":"10.1016\/j.jhep.2016.04.016","article-title":"Treatment of chronic hepatitis D with the entry inhibitor myrcludex B: First results of a phase Ib\/IIa study","volume":"65","author":"Bogomolov","year":"2016","journal-title":"J. Hepatol."},{"key":"2023072804453187400_bib8","doi-asserted-by":"publisher","first-page":"816","DOI":"10.15252\/emmm.201607006","article-title":"Transcriptional response to hepatitis C virus infection and interferon-alpha treatment in the human liver","volume":"9","author":"Boldanova","year":"2017","journal-title":"EMBO Mol. Med."},{"key":"2023072804453187400_bib9","doi-asserted-by":"publisher","first-page":"731","DOI":"10.1084\/jem.20031482","article-title":"Spontaneous development of psoriasis in a new animal model shows an essential role for resident T cells and tumor necrosis factor-alpha","volume":"199","author":"Boyman","year":"2004","journal-title":"J. Exp. Med."},{"key":"2023072804453187400_bib10","doi-asserted-by":"publisher","first-page":"5079","DOI":"10.4049\/jimmunol.168.10.5079","article-title":"Visualization of lymphotoxin-\u03b2 and lymphotoxin-\u03b2 receptor expression in mouse embryos","volume":"168","author":"Browning","year":"2002","journal-title":"J. Immunol."},{"key":"2023072804453187400_bib11","doi-asserted-by":"publisher","first-page":"5374","DOI":"10.1128\/JVI.79.9.5374-5385.2005","article-title":"Gamma interferon-dependent, noncytolytic clearance of sindbis virus infection from neurons in vitro","volume":"79","author":"Burdeinick-Kerr","year":"2005","journal-title":"J. Virol."},{"key":"2023072804453187400_bib12","doi-asserted-by":"publisher","first-page":"3429","DOI":"10.1128\/JVI.02381-08","article-title":"Noncytolytic clearance of sindbis virus infection from neurons by gamma interferon is dependent on Jak\/STAT signaling","volume":"83","author":"Burdeinick-Kerr","year":"2009","journal-title":"J. Virol."},{"key":"2023072804453187400_bib13","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1007\/978-1-4939-6700-1_10","article-title":"Highly Sensitive Detection of HBV RNA in Liver Tissue by In Situ Hybridization","volume":"1540","author":"Calabrese","year":"2017","journal-title":"Methods Mol. Biol."},{"key":"2023072804453187400_bib14","doi-asserted-by":"publisher","first-page":"1964","DOI":"10.1038\/s41564-019-0509-3","article-title":"DNA mismatch repair is required for the host innate response and controls cellular fate after influenza virus infection","volume":"4","author":"Chambers","year":"2019","journal-title":"Nat. Microbiol."},{"key":"2023072804453187400_bib15","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1016\/j.ejca.2018.02.010","article-title":"Aflatoxin B1 exposure increases the risk of hepatocellular carcinoma associated with hepatitis C virus infection or alcohol consumption","volume":"94","author":"Chu","year":"2018","journal-title":"Eur. J. Cancer."},{"key":"2023072804453187400_bib16","doi-asserted-by":"publisher","first-page":"1552","DOI":"10.1128\/MCB.3.9.1552","article-title":"Changes in liver-specific compared to common gene transcription during primary culture of mouse hepatocytes","volume":"3","author":"Clayton","year":"1983","journal-title":"Mol. Cell. Biol."},{"key":"2023072804453187400_bib17","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1038\/238335a0","article-title":"Requirement for theta-bearing cells in lymphocytic choriomeningitis virus-induced central nervous system disease","volume":"238","author":"Cole","year":"1972","journal-title":"Nature."},{"key":"2023072804453187400_bib18","doi-asserted-by":"publisher","first-page":"9415","DOI":"10.1128\/JVI.75.19.9415-9426.2001","article-title":"RING finger Z protein of lymphocytic choriomeningitis virus (LCMV) inhibits transcription and RNA replication of an LCMV S-segment minigenome","volume":"75","author":"Cornu","year":"2001","journal-title":"J. Virol."},{"key":"2023072804453187400_bib19","doi-asserted-by":"publisher","first-page":"2979","DOI":"10.1128\/JVI.78.6.2979-2983.2004","article-title":"Cells expressing the RING finger Z protein are resistant to arenavirus infection","volume":"78","author":"Cornu","year":"2004","journal-title":"J. Virol."},{"key":"2023072804453187400_bib20","doi-asserted-by":"publisher","first-page":"474","DOI":"10.1016\/0042-6822(83)90185-X","article-title":"Response of cells persistently infected with arenaviruses to superinfection with homotypic and heterotypic viruses","volume":"129","author":"Damonte","year":"1983","journal-title":"Virology."},{"key":"2023072804453187400_bib21","doi-asserted-by":"publisher","first-page":"11734","DOI":"10.1128\/JVI.01613-15","article-title":"The Nucleoprotein Is Required for Lymphocytic Choriomeningitis Virus-Based Vaccine Vector Immunogenicity","volume":"89","author":"Darbre","year":"2015","journal-title":"J. Virol."},{"key":"2023072804453187400_bib22","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3009512","article-title":"Broadly neutralizing antibodies abrogate established hepatitis C virus infection","volume":"6","author":"de Jong","year":"2014","journal-title":"Sci. Transl. Med."},{"key":"2023072804453187400_bib23","doi-asserted-by":"publisher","first-page":"955","DOI":"10.1128\/jvi.2.10.955-961.1968","article-title":"Defectiveness of interferon production and of rubella virus interference in a line of African green monkey kidney cells (Vero)","volume":"2","author":"Desmyter","year":"1968","journal-title":"J. Virol."},{"key":"2023072804453187400_bib24","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","article-title":"STAR: ultrafast universal RNA-seq aligner","volume":"29","author":"Dobin","year":"2013","journal-title":"Bioinformatics."},{"key":"2023072804453187400_bib25","doi-asserted-by":"publisher","first-page":"895","DOI":"10.1038\/s41467-017-01169-0","article-title":"Dynamic regulation of canonical TGF\u03b2 signalling by endothelial transcription factor ERG protects from liver fibrogenesis","volume":"8","author":"Dufton","year":"2017","journal-title":"Nat. Commun."},{"key":"2023072804453187400_bib26","doi-asserted-by":"publisher","first-page":"779","DOI":"10.1038\/s41467-019-08617-z","article-title":"Non-lytic clearance of influenza B virus from infected cells preserves epithelial barrier function","volume":"10","author":"Dumm","year":"2019","journal-title":"Nat. Commun."},{"key":"2023072804453187400_bib27","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1002\/hep.28535","article-title":"Risk of hepatocellular carcinoma after sustained virological response in Veterans with hepatitis C virus infection","volume":"64","author":"El-Serag","year":"2016","journal-title":"Hepatology."},{"key":"2023072804453187400_bib28","doi-asserted-by":"publisher","first-page":"507","DOI":"10.1007\/s00705-003-0227-1","article-title":"Resistance to superinfection of Vero cells persistently infected with Junin virus","volume":"149","author":"Ellenberg","year":"2004","journal-title":"Arch. Virol."},{"key":"2023072804453187400_bib29","doi-asserted-by":"publisher","first-page":"11650","DOI":"10.1128\/JVI.00955-07","article-title":"Early antibodies specific for the neutralizing epitope on the receptor binding subunit of the lymphocytic choriomeningitis virus glycoprotein fail to neutralize the virus","volume":"81","author":"Eschli","year":"2007","journal-title":"J. Virol."},{"key":"2023072804453187400_bib30","doi-asserted-by":"publisher","first-page":"4663","DOI":"10.1073\/pnas.0600652103","article-title":"Recovery of an arenavirus entirely from RNA polymerase I\/II-driven cDNA","volume":"103","author":"Flatz","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"2023072804453187400_bib31","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1038\/nm.2104","article-title":"Development of replication-defective lymphocytic choriomeningitis virus vectors for the induction of potent CD8+ T cell immunity","volume":"16","author":"Flatz","year":"2010","journal-title":"Nat. Med."},{"key":"2023072804453187400_bib32","doi-asserted-by":"publisher","first-page":"1425","DOI":"10.1084\/jem.174.6.1425","article-title":"Immune response against lymphocytic choriomeningitis virus infection in mice without CD8 expression","volume":"174","author":"Fung-Leung","year":"1991","journal-title":"J. Exp. Med."},{"key":"2023072804453187400_bib33","doi-asserted-by":"publisher","first-page":"1363","DOI":"10.1101\/gr.240663.118","article-title":"Benchmark and integration of resources for the estimation of human transcription factor activities","volume":"29","author":"Garcia-Alonso","year":"2019","journal-title":"Genome Res."},{"key":"2023072804453187400_bib34","doi-asserted-by":"crossref","first-page":"3331","DOI":"10.4049\/jimmunol.149.10.3331","article-title":"Control of acute infection with lymphocytic choriomeningitis virus in mice that cannot present an immunodominant viral cytotoxic T lymphocyte epitope","volume":"149","author":"Gegin","year":"1992","journal-title":"J. Immunol."},{"key":"2023072804453187400_bib35","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1007\/s12026-009-8143-4","article-title":"Recovery from viral encephalomyelitis: immune-mediated noncytolytic virus clearance from neurons","volume":"47","author":"Griffin","year":"2010","journal-title":"Immunol. Res."},{"key":"2023072804453187400_bib36","doi-asserted-by":"publisher","first-page":"4748","DOI":"10.1128\/JVI.73.6.4748-4754.1999","article-title":"Role of the individual interferon systems and specific immunity in mice in controlling systemic dissemination of attenuated pseudorabies virus infection","volume":"73","author":"Grob","year":"1999","journal-title":"J. Virol."},{"key":"2023072804453187400_bib37","doi-asserted-by":"publisher","first-page":"2847","DOI":"10.1093\/bioinformatics\/btw313","article-title":"Complex heatmaps reveal patterns and correlations in multidimensional genomic data","volume":"32","author":"Gu","year":"2016","journal-title":"Bioinformatics."},{"key":"2023072804453187400_bib38","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1146\/annurev.immunol.19.1.65","article-title":"Noncytolytic control of viral infections by the innate and adaptive immune response","volume":"19","author":"Guidotti","year":"2001","journal-title":"Annu. Rev. Immunol."},{"key":"2023072804453187400_bib39","doi-asserted-by":"publisher","first-page":"3764","DOI":"10.1073\/pnas.91.9.3764","article-title":"Cytotoxic T lymphocytes inhibit hepatitis B virus gene expression by a noncytolytic mechanism in transgenic mice","volume":"91","author":"Guidotti","year":"1994","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"2023072804453187400_bib40","doi-asserted-by":"publisher","first-page":"4589","DOI":"10.1073\/pnas.93.10.4589","article-title":"Viral cross talk: intracellular inactivation of the hepatitis B virus during an unrelated viral infection of the liver","volume":"93","author":"Guidotti","year":"1996","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"2023072804453187400_bib41","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/S1074-7613(00)80295-2","article-title":"Intracellular inactivation of the hepatitis B virus by cytotoxic T lymphocytes","volume":"4","author":"Guidotti","year":"1996","journal-title":"Immunity."},{"key":"2023072804453187400_bib42","doi-asserted-by":"publisher","first-page":"1555","DOI":"10.1084\/jem.189.10.1555","article-title":"Noncytopathic clearance of lymphocytic choriomeningitis virus from the hepatocyte","volume":"189","author":"Guidotti","year":"1999","journal-title":"J. Exp. Med."},{"key":"2023072804453187400_bib43","doi-asserted-by":"publisher","first-page":"825","DOI":"10.1126\/science.284.5415.825","article-title":"Viral clearance without destruction of infected cells during acute HBV infection","volume":"284","author":"Guidotti","year":"1999","journal-title":"Science."},{"key":"2023072804453187400_bib44","doi-asserted-by":"publisher","first-page":"2313","DOI":"10.1053\/j.gastro.2019.02.038","article-title":"HCV-Induced Epigenetic Changes Associated With Liver Cancer Risk Persist After Sustained Virologic Response","volume":"156","author":"Hamdane","year":"2019","journal-title":"Gastroenterology."},{"key":"2023072804453187400_bib45","doi-asserted-by":"publisher","first-page":"3861","DOI":"10.1073\/pnas.1522376113","article-title":"Club cells surviving influenza A virus infection induce temporary nonspecific antiviral immunity","volume":"113","author":"Hamilton","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"2023072804453187400_bib46","doi-asserted-by":"publisher","first-page":"13509","DOI":"10.1128\/JVI.79.21.13509-13518.2005","article-title":"CD8 T cells require gamma interferon to clear borna disease virus from the brain and prevent immune system-mediated neuronal damage","volume":"79","author":"Hausmann","year":"2005","journal-title":"J. Virol."},{"key":"2023072804453187400_bib47","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1016\/j.ccr.2009.08.021","article-title":"A lymphotoxin-driven pathway to hepatocellular carcinoma","volume":"16","author":"Haybaeck","year":"2009","journal-title":"Cancer Cell."},{"key":"2023072804453187400_bib48","doi-asserted-by":"publisher","first-page":"1707","DOI":"10.1084\/jem.20140488","article-title":"Long-term survival of influenza virus infected club cells drives immunopathology","volume":"211","author":"Heaton","year":"2014","journal-title":"J. Exp. Med."},{"key":"2023072804453187400_bib49","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0087906","article-title":"Human but not mouse hepatocytes respond to interferon-lambda in vivo","volume":"9","author":"Hermant","year":"2014","journal-title":"PLoS One."},{"key":"2023072804453187400_bib50","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1186\/s13059-020-1949-z","article-title":"Robustness and applicability of transcription factor and pathway analysis tools on single-cell RNA-seq data","volume":"21","author":"Holland","year":"2020","journal-title":"Genome Biol."},{"key":"2023072804453187400_bib51","doi-asserted-by":"publisher","first-page":"1024","DOI":"10.1053\/j.gastro.2013.01.021","article-title":"Prognostic gene expression signature for patients with hepatitis C-related early-stage cirrhosis","volume":"144","author":"Hoshida","year":"2013","journal-title":"Gastroenterology."},{"key":"2023072804453187400_bib52","doi-asserted-by":"publisher","first-page":"479","DOI":"10.1101\/SQB.1962.027.001.046","article-title":"The biology of lymphocytic choriomeningitis infection: virus-induced immune disease","volume":"27","author":"Hotchin","year":"1962","journal-title":"Cold Spring Harb. Symp. Quant. Biol."},{"key":"2023072804453187400_bib53","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1007\/978-3-642-65681-1_8","author":"Hotchin","year":"1973"},{"key":"2023072804453187400_bib54","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1038\/newbio241270a0","article-title":"Transient virus infection: spontaneous recovery mechanism of lymphocytic choriomeningitis virrus-infected cells","volume":"241","author":"Hotchin","year":"1973","journal-title":"Nat. New Biol."},{"key":"2023072804453187400_bib55","first-page":"304","article-title":"Cyclical phenomena in persistent virus infection","volume":"15","author":"Hotchin","year":"1974","journal-title":"J. Reticuloendothel. Soc."},{"key":"2023072804453187400_bib56","doi-asserted-by":"publisher","first-page":"1283","DOI":"10.1126\/science.1891717","article-title":"Viral persistence in neurons explained by lack of major histocompatibility class I expression","volume":"253","author":"Joly","year":"1991","journal-title":"Science."},{"key":"2023072804453187400_bib57","doi-asserted-by":"publisher","first-page":"15327","DOI":"10.1038\/ncomms15327","article-title":"Replicating viral vector platform exploits alarmin signals for potent CD8+ T cell-mediated tumour immunotherapy","volume":"8","author":"Kallert","year":"2017","journal-title":"Nat. Commun."},{"key":"2023072804453187400_bib58","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02241-17","article-title":"Visualization of Arenavirus RNA Species in Individual Cells by Single-Molecule Fluorescence In Situ Hybridization Suggests a Model of Cyclical Infection and Clearance during Persistence","volume":"92","author":"King","year":"2018","journal-title":"J. Virol."},{"key":"2023072804453187400_bib59","doi-asserted-by":"publisher","first-page":"19743","DOI":"10.1073\/pnas.1112742108","article-title":"Arenavirus Z protein controls viral RNA synthesis by locking a polymerase-promoter complex","volume":"108","author":"Kranzusch","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"2023072804453187400_bib60","doi-asserted-by":"publisher","first-page":"770","DOI":"10.1038\/213770a0","article-title":"A carrier state of lymphocytic choriomeningitis virus in L cell cultures","volume":"213","author":"Lehmann-Grube","year":"1967","journal-title":"Nature."},{"key":"2023072804453187400_bib61","doi-asserted-by":"crossref","first-page":"608","DOI":"10.4049\/jimmunol.134.1.608","article-title":"Mechanism of recovery from acute virus infection. I. Role of T lymphocytes in the clearance of lymphocytic choriomeningitis virus from spleens of mice","volume":"134","author":"Lehmann-Grube","year":"1985","journal-title":"J. Immunol."},{"key":"2023072804453187400_bib62","doi-asserted-by":"publisher","first-page":"923","DOI":"10.1093\/bioinformatics\/btt656","article-title":"featureCounts: an efficient general purpose program for assigning sequence reads to genomic features","volume":"30","author":"Liao","year":"2014","journal-title":"Bioinformatics."},{"key":"2023072804453187400_bib63","doi-asserted-by":"publisher","first-page":"619","DOI":"10.1016\/j.chom.2016.04.008","article-title":"Epigenetics and Genetics of Viral Latency","volume":"19","author":"Lieberman","year":"2016","journal-title":"Cell Host Microbe."},{"key":"2023072804453187400_bib64","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1038\/nature06293","article-title":"Transgenic strategies for combinatorial expression of fluorescent proteins in the nervous system","volume":"450","author":"Livet","year":"2007","journal-title":"Nature."},{"key":"2023072804453187400_bib65","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1002\/eji.200636745","article-title":"Faithful activation of an extra-bright red fluorescent protein in \u201cknock-in\u201d Cre-reporter mice ideally suited for lineage tracing studies","volume":"37","author":"Luche","year":"2007","journal-title":"Eur. J. Immunol."},{"key":"2023072804453187400_bib66","doi-asserted-by":"publisher","first-page":"1221","DOI":"10.1126\/science.1243462","article-title":"Specific and nonhepatotoxic degradation of nuclear hepatitis B virus cccDNA","volume":"343","author":"Lucifora","year":"2014","journal-title":"Science."},{"key":"2023072804453187400_bib67","doi-asserted-by":"publisher","first-page":"4288","DOI":"10.1093\/nar\/gks042","article-title":"Differential expression analysis of multifactor RNA-Seq experiments with respect to biological variation","volume":"40","author":"McCarthy","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"2023072804453187400_bib68","doi-asserted-by":"publisher","first-page":"869","DOI":"10.1016\/0092-8674(92)90030-G","article-title":"RAG-1-deficient mice have no mature B and T lymphocytes","volume":"68","author":"Mombaerts","year":"1992","journal-title":"Cell."},{"key":"2023072804453187400_bib69","doi-asserted-by":"publisher","first-page":"2279","DOI":"10.1128\/MCB.6.6.2279","article-title":"Transcriptional and posttranscriptional regulation of exogenous human beta interferon gene in simian cells defective in interferon synthesis","volume":"6","author":"Mosca","year":"1986","journal-title":"Mol. Cell. Biol."},{"key":"2023072804453187400_bib70","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.abb1817","article-title":"T cell engagement of cross-presenting microglia protects the brain from a nasal virus infection","volume":"5","author":"Moseman","year":"2020","journal-title":"Sci. Immunol."},{"key":"2023072804453187400_bib71","doi-asserted-by":"publisher","first-page":"879","DOI":"10.1016\/j.ccell.2016.11.004","article-title":"Molecular Liver Cancer Prevention in Cirrhosis by Organ Transcriptome Analysis and Lysophosphatidic Acid Pathway Inhibition","volume":"30","author":"Nakagawa","year":"2016","journal-title":"Cancer Cell."},{"key":"2023072804453187400_bib72","doi-asserted-by":"publisher","first-page":"360","DOI":"10.1038\/300360a0","article-title":"Restricted expression of viral glycoprotein in cells of persistently infected mice","volume":"300","author":"Oldstone","year":"1982","journal-title":"Nature."},{"key":"2023072804453187400_bib73","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1038\/321239a0","article-title":"Cytoimmunotherapy for persistent virus infection reveals a unique clearance pattern from the central nervous system","volume":"321","author":"Oldstone","year":"1986","journal-title":"Nature."},{"key":"2023072804453187400_bib74","doi-asserted-by":"publisher","first-page":"534","DOI":"10.1080\/19440049.2012.751630","article-title":"Global geographical overlap of aflatoxin and hepatitis C: controlling risk factors for liver cancer worldwide","volume":"30","author":"Palliyaguru","year":"2013","journal-title":"Food Addit. Contam. Part A Chem. Anal. Control Expo. Risk Assess."},{"key":"2023072804453187400_bib75","doi-asserted-by":"crossref","first-page":"1641","DOI":"10.4049\/jimmunol.162.3.1641","article-title":"IFN-\u03b3 is required for viral clearance from central nervous system oligodendroglia","volume":"162","author":"Parra","year":"1999","journal-title":"J. Immunol."},{"key":"2023072804453187400_bib76","doi-asserted-by":"publisher","first-page":"4497","DOI":"10.1128\/JVI.76.9.4497-4506.2002","article-title":"Immune-mediated protection from measles virus-induced central nervous system disease is noncytolytic and gamma interferon dependent","volume":"76","author":"Patterson","year":"2002","journal-title":"J. Virol."},{"key":"2023072804453187400_bib77","doi-asserted-by":"publisher","first-page":"749","DOI":"10.1093\/intimm\/dxq061","article-title":"Innate and adaptive immune control of genetically engineered live-attenuated arenavirus vaccine prototypes","volume":"22","author":"Pinschewer","year":"2010","journal-title":"Int. Immunol."},{"key":"2023072804453187400_bib78","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1038\/342559a0","article-title":"Tolerance induction in double specific T-cell receptor transgenic mice varies with antigen","volume":"342","author":"Pircher","year":"1989","journal-title":"Nature."},{"key":"2023072804453187400_bib79","doi-asserted-by":"publisher","first-page":"6874","DOI":"10.1073\/pnas.94.13.6874","article-title":"A critical role for neutralizing-antibody-producing B cells, CD4(+) T cells, and interferons in persistent and acute infections of mice with lymphocytic choriomeningitis virus: implications for adoptive immunotherapy of virus carriers","volume":"94","author":"Planz","year":"1997","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"2023072804453187400_bib80","doi-asserted-by":"publisher","first-page":"11346","DOI":"10.1038\/srep11346","article-title":"Generation of a variety of stable Influenza A reporter viruses by genetic engineering of the NS gene segment","volume":"5","author":"Reuther","year":"2015","journal-title":"Sci. Rep."},{"key":"2023072804453187400_bib81","doi-asserted-by":"publisher","first-page":"3331","DOI":"10.1016\/S0264-410X(01)00028-7","article-title":"Neonatal and early life vaccinology","volume":"19","author":"Siegrist","year":"2001","journal-title":"Vaccine."},{"key":"2023072804453187400_bib82","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1186\/1471-213X-1-4","article-title":"Cre reporter strains produced by targeted insertion of EYFP and ECFP into the ROSA26 locus","volume":"1","author":"Srinivas","year":"2001","journal-title":"BMC Dev. Biol."},{"key":"2023072804453187400_bib83","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aav5519","article-title":"Brain-resident memory T cells generated early in life predispose to autoimmune disease in mice","volume":"11","author":"Steinbach","year":"2019","journal-title":"Sci. Transl. Med."},{"key":"2023072804453187400_bib84","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1016\/j.jhep.2020.09.022","article-title":"T cell immunity to hepatitis C virus: Lessons for a prophylactic vaccine","volume":"74","author":"Thimme","year":"2021","journal-title":"J. Hepatol."},{"key":"2023072804453187400_bib85","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1128\/JVI.77.1.68-76.2003","article-title":"CD8(+) T cells mediate viral clearance and disease pathogenesis during acute hepatitis B virus infection","volume":"77","author":"Thimme","year":"2003","journal-title":"J. Virol."},{"key":"2023072804453187400_bib86","doi-asserted-by":"publisher","first-page":"7079","DOI":"10.1182\/blood-2010-12-317990","article-title":"ERG promotes T-acute lymphoblastic leukemia and is transcriptionally regulated in leukemic cells by a stem cell enhancer","volume":"117","author":"Thoms","year":"2011","journal-title":"Blood."},{"key":"2023072804453187400_bib87","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1006\/viro.1993.1613","article-title":"Cytotoxic T lymphocytes cleanse viral gene products from individually infected neurons and lymphocytes in mice persistently infected with lymphocytic choriomeningitis virus","volume":"197","author":"Tishon","year":"1993","journal-title":"Virology."},{"key":"2023072804453187400_bib88","doi-asserted-by":"publisher","first-page":"244","DOI":"10.1006\/viro.1995.1477","article-title":"An essential role for type 1 interferon-\u03b3 in terminating persistent viral infection","volume":"212","author":"Tishon","year":"1995","journal-title":"Virology."},{"key":"2023072804453187400_bib89","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1084\/jem.64.2.183","article-title":"The Epidemiology of Lymphocytic Choriomeningitis in White Mice","volume":"64","author":"Traub","year":"1936","journal-title":"J. Exp. Med."},{"key":"2023072804453187400_bib90","doi-asserted-by":"publisher","first-page":"992","DOI":"10.1084\/jem.153.4.992","article-title":"Effector T lymphocytes in lymphocytic choriomeningitis virus-infected mice. Cytolytic activity of Lyt-23 spleen cells in vitro does not correlate with elimination of infectious virus from spleens","volume":"153","author":"Varho","year":"1981","journal-title":"J. Exp. Med."},{"key":"2023072804453187400_bib91","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1111\/j.1699-0463.1963.tb05115.x","article-title":"STUDIES ON IMMUNOLOGICAL TOLERANCE TO LCM VIRUS. 2. TREATMENT OF VIRUS CARRIER MICE BY ADOPTIVE IMMUNIZATION","volume":"57","author":"Volkert","year":"1963","journal-title":"Acta Pathol. Microbiol. Scand."},{"key":"2023072804453187400_bib92","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1084\/jem.127.2.327","article-title":"The provocation of latent lymphocytic choriomeningitis virus infections in mice by treatment with antilymphocytic serum","volume":"127","author":"Volkert","year":"1968","journal-title":"J. Exp. Med."},{"key":"2023072804453187400_bib93","doi-asserted-by":"publisher","first-page":"787","DOI":"10.1146\/annurev.immunol.23.021704.115719","article-title":"Network communications: lymphotoxins, LIGHT, and TNF","volume":"23","author":"Ware","year":"2005","journal-title":"Annu. Rev. Immunol."},{"key":"2023072804453187400_bib94","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1007\/BF01309275","article-title":"Persistent infection of cultivated cells with lymphocytic choriomeningitis virus: regulation of virus replication. Brief report","volume":"77","author":"Weber","year":"1983","journal-title":"Arch. Virol."},{"key":"2023072804453187400_bib95","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1099\/0022-1317-14-2-177","article-title":"Determinants of lymphocytic choriomeningitis interference","volume":"14","author":"Welsh","year":"1972","journal-title":"J. Gen. Virol."},{"key":"2023072804453187400_bib96","doi-asserted-by":"publisher","first-page":"344","DOI":"10.1038\/s41586-019-0896-x","article-title":"PU.1 controls fibroblast polarization and tissue fibrosis","volume":"566","author":"Wohlfahrt","year":"2019","journal-title":"Nature."},{"key":"2023072804453187400_bib97","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1016\/j.virol.2018.01.013","article-title":"Mammarenaviruses deleted from their Z gene are replicative and produce an infectious progeny in BHK-21 cells","volume":"518","author":"Zaza","year":"2018","journal-title":"Virology."},{"key":"2023072804453187400_bib98","first-page":"1","article-title":"Lymphocytic choriomeningitis virus and immunology","volume":"263","author":"Zinkernagel","year":"2002","journal-title":"Curr. Top. Microbiol. Immunol."}],"container-title":["Journal of Experimental Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/doi\/10.1084\/jem.20210408\/1828155\/jem_20210408.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/doi\/10.1084\/jem.20210408\/1828155\/jem_20210408.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,28]],"date-time":"2023-07-28T04:48:53Z","timestamp":1690519733000},"score":1,"resource":{"primary":{"URL":"https:\/\/rupress.org\/jem\/article\/218\/10\/e20210408\/212556\/Persistent-RNA-virus-infection-is-short-lived-at"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,16]]},"references-count":98,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2021,10,4]]}},"URL":"https:\/\/doi.org\/10.1084\/jem.20210408","relation":{},"ISSN":["0022-1007","1540-9538"],"issn-type":[{"value":"0022-1007","type":"print"},{"value":"1540-9538","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,16]]},"article-number":"e20210408"}}