{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T15:52:38Z","timestamp":1787068358429,"version":"build-2736575974"},"reference-count":64,"publisher":"Rockefeller University Press","issue":"12","license":[{"start":{"date-parts":[[2020,9,3]],"date-time":"2020-09-03T00:00:00Z","timestamp":1599091200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.rupress.org\/terms\/"},{"start":{"date-parts":[[2021,6,7]],"date-time":"2021-06-07T00:00:00Z","timestamp":1623024000000},"content-version":"vor","delay-in-days":277,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["FDN148386"],"award-info":[{"award-number":["FDN148386"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AI085043"],"award-info":[{"award-number":["AI085043"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Scotiabank Research Chair"},{"name":"Fonds de la Recherche en Sant\u00e9 du Qu\u00e9bec"}],"content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,12,7]]},"abstract":"<jats:p>Many pathogens subvert intestinal immunity to persist within the gastrointestinal tract (GIT); yet, the underlying mechanisms that enable sanctuary specifically in this reservoir are unclear. Using mass cytometry and network analysis, we demonstrate that chronic LCMV infection of the GIT leads to dysregulated microbial composition, a cascade of metabolic alterations, increased susceptibility to GI disease, and a system-wide recalibration of immune composition that defines viral persistence. Chronic infection led to outgrowth of activated Tbet\u2013expressing T reg cell populations unique to the GIT and the rapid erosion of pathogen-specific CD8 tissue-resident memory T cells. Mechanistically, T reg cells and coinhibitory receptors maintained long-term viral sanctuary within the GIT, and their targeting reactivated T cells and eliminated this viral reservoir. Thus, our data provide a high-dimensional definition of the mechanisms of immune regulation that chronic viruses implement to exploit the unique microenvironment of the GIT and identify T reg cells as key modulators of viral persistence in the intestinal tract.<\/jats:p>","DOI":"10.1084\/jem.20191473","type":"journal-article","created":{"date-parts":[[2020,1,22]],"date-time":"2020-01-22T02:21:20Z","timestamp":1579659680000},"update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":14,"title":["A network of immune and microbial modifications underlies viral persistence in the gastrointestinal tract"],"prefix":"10.1084","volume":"217","author":[{"given":"Bethany L.","family":"Macleod","sequence":"first","affiliation":[{"name":"Princess Margaret Cancer Center, University Health Network, Toronto, Ontario, Canada 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heidi J.","family":"Elsaesser","sequence":"additional","affiliation":[{"name":"Princess Margaret Cancer Center, University Health Network, Toronto, Ontario, Canada 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura M.","family":"Snell","sequence":"additional","affiliation":[{"name":"Princess Margaret Cancer Center, University Health Network, Toronto, Ontario, Canada 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Russell J.","family":"Dickson","sequence":"additional","affiliation":[{"name":"Princess Margaret Cancer Center, University Health Network, Toronto, Ontario, Canada 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengdi","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Toronto, Toronto, Ontario, Canada 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1905-9697","authenticated-orcid":true,"given":"Kebria","family":"Hezaveh","sequence":"additional","affiliation":[{"name":"Princess Margaret Cancer Center, University Health Network, Toronto, Ontario, Canada 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenxi","family":"Xu","sequence":"additional","affiliation":[{"name":"Princess Margaret Cancer Center, University Health Network, Toronto, Ontario, Canada 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1980-161X","authenticated-orcid":true,"given":"Akash","family":"Kothari","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Toronto, Toronto, Ontario, Canada 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tracy L.","family":"McGaha","sequence":"additional","affiliation":[{"name":"Princess Margaret Cancer Center, University Health Network, Toronto, Ontario, Canada 1"},{"name":"Department of Immunology, University of Toronto, Toronto, Ontario, Canada 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia J.","family":"Guidos","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Toronto, Toronto, Ontario, Canada 2"},{"name":"Program in Developmental and Stem Cell Biology, Hospital for Sick Children Research Institute, Toronto, Ontario, Canada 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7763-8764","authenticated-orcid":true,"given":"David G.","family":"Brooks","sequence":"additional","affiliation":[{"name":"Princess Margaret Cancer Center, University Health Network, Toronto, Ontario, Canada 1"},{"name":"Department of Immunology, University of Toronto, Toronto, Ontario, Canada 2"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2020,9,3]]},"reference":[{"key":"2023072717400733600_bib1","doi-asserted-by":"publisher","first-page":"1047","DOI":"10.1016\/j.molmed.2016.10.003","article-title":"Norovirus regulation by host and microbe","volume":"22","author":"Baldridge","year":"2016","journal-title":"Trends Mol. Med"},{"key":"2023072717400733600_bib2","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1097\/COH.0000000000000429","article-title":"Altered gut microbiome composition in HIV infection: causes, effects and potential intervention","volume":"13","author":"Bandera","year":"2018","journal-title":"Curr. Opin. HIV AIDS"},{"key":"2023072717400733600_bib3","doi-asserted-by":"publisher","first-page":"1029","DOI":"10.1016\/j.immuni.2018.04.026","article-title":"Epigenomic-guided mass cytometry profiling reveals disease-specific features of exhausted CD8 T cells","volume":"48","author":"Bengsch","year":"2018","journal-title":"Immunity"},{"key":"2023072717400733600_bib4","doi-asserted-by":"publisher","first-page":"18224","DOI":"10.18632\/oncotarget.24804","article-title":"Increased gut permeability in cancer cachexia: mechanisms and clinical relevance","volume":"9","author":"Bindels","year":"2018","journal-title":"Oncotarget"},{"key":"2023072717400733600_bib5","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1038\/ni1316","article-title":"HIV disease: fallout from a mucosal catastrophe?","volume":"7","author":"Brenchley","year":"2006","journal-title":"Nat. Immunol"},{"key":"2023072717400733600_bib6","doi-asserted-by":"publisher","first-page":"1675","DOI":"10.1172\/JCI26856","article-title":"Reprogramming of antiviral T cells prevents inactivation and restores T cell activity during persistent viral infection","volume":"116","author":"Brooks","year":"2006","journal-title":"J. Clin. Invest"},{"key":"2023072717400733600_bib7","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1038\/nmeth.f.303","article-title":"QIIME allows analysis of high-throughput community sequencing data","volume":"7","author":"Caporaso","year":"2010","journal-title":"Nat. Methods"},{"key":"2023072717400733600_bib8","doi-asserted-by":"publisher","first-page":"1621","DOI":"10.1038\/ismej.2012.8","article-title":"Ultra-high-throughput microbial community analysis on the Illumina HiSeq and MiSeq platforms","volume":"6","author":"Caporaso","year":"2012","journal-title":"ISME J"},{"key":"2023072717400733600_bib9","doi-asserted-by":"publisher","first-page":"4866","DOI":"10.4049\/jimmunol.1200402","article-title":"Antigen-independent differentiation and maintenance of effector-like resident memory T cells in tissues","volume":"188","author":"Casey","year":"2012","journal-title":"J. Immunol"},{"key":"2023072717400733600_bib10","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1186\/1471-2105-14-128","article-title":"Enrichr: interactive and collaborative HTML5 gene list enrichment analysis tool","volume":"14","author":"Chen","year":"2013","journal-title":"BMC Bioinformatics"},{"key":"2023072717400733600_bib11","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1005356","article-title":"Type I and type II interferon coordinately regulate suppressive dendritic cell fate and function during viral persistence","volume":"12","author":"Cunningham","year":"2016","journal-title":"PLoS Pathog"},{"key":"2023072717400733600_bib12","doi-asserted-by":"publisher","first-page":"354","DOI":"10.1016\/j.cell.2015.08.030","article-title":"Microbiota-dependent sequelae of acute infection compromise tissue-specific immunity","volume":"163","author":"Da Fonseca","year":"2015","journal-title":"Cell"},{"key":"2023072717400733600_bib13","doi-asserted-by":"publisher","first-page":"280","DOI":"10.1016\/j.chom.2016.02.012","article-title":"Dissecting how CD4 T cells are lost during HIV infection","volume":"19","author":"Doitsh","year":"2016","journal-title":"Cell Host Microbe"},{"key":"2023072717400733600_bib14","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1038\/nrmicro3552","article-title":"Gut biogeography of the bacterial microbiota","volume":"14","author":"Donaldson","year":"2016","journal-title":"Nat. Rev. Microbiol"},{"issue":"sup1","key":"2023072717400733600_bib15","doi-asserted-by":"publisher","first-page":"S65","DOI":"10.1080\/16070658.2010.11734275","article-title":"The gastrointestinal tract and HIV pathogenesis","volume":"23","author":"Downs","year":"2010","journal-title":"South Afr. J. Clin. Nutr"},{"key":"2023072717400733600_bib16","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/j.humic.2016.10.001","article-title":"Impact of HIV on the human gut microbiota: challenges and perspectives","volume":"2","author":"Dubourg","year":"2016","journal-title":"Hum. Microb. J"},{"key":"2023072717400733600_bib17","doi-asserted-by":"publisher","first-page":"996","DOI":"10.1038\/nmeth.2604","article-title":"UPARSE: highly accurate OTU sequences from microbial amplicon reads","volume":"10","author":"Edgar","year":"2013","journal-title":"Nat. Methods"},{"key":"2023072717400733600_bib18","doi-asserted-by":"publisher","first-page":"1271","DOI":"10.1038\/nm.4411","article-title":"Defining total-body AIDS-virus burden with implications for curative strategies","volume":"23","author":"Estes","year":"2017","journal-title":"Nat. Med"},{"key":"2023072717400733600_bib19","doi-asserted-by":"publisher","first-page":"987","DOI":"10.1084\/jem.20101773","article-title":"Viral persistence redirects CD4 T cell differentiation toward T follicular helper cells","volume":"208","author":"Fahey","year":"2011","journal-title":"J. Exp. Med"},{"key":"2023072717400733600_bib20","doi-asserted-by":"publisher","first-page":"1211","DOI":"10.1084\/jem.20162014","article-title":"Tissue adaptation: Implications for gut immunity and tolerance","volume":"214","author":"Faria","year":"2017","journal-title":"J. Exp. Med"},{"key":"2023072717400733600_bib21","doi-asserted-by":"publisher","first-page":"1886","DOI":"10.1002\/eji.201344279","article-title":"IRF4 at the crossroads of effector T-cell fate decision","volume":"44","author":"Huber","year":"2014","journal-title":"Eur. J. Immunol"},{"key":"2023072717400733600_bib22","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1038\/nature19330","article-title":"Defining CD8+ T cells that provide the proliferative burst after PD-1 therapy","volume":"537","author":"Im","year":"2016","journal-title":"Nature"},{"key":"2023072717400733600_bib23","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1016\/B978-0-444-53488-0.00018-3","article-title":"Enterovirus\/picornavirus infections","volume":"123","author":"Jubelt","year":"2014","journal-title":"Handb. Clin. Neurol"},{"key":"2023072717400733600_bib24","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1097\/QAI.0b013e318074ef6e","article-title":"The relation between symptoms, viral load, and viral load set point in primary HIV infection","volume":"45","author":"Kelley","year":"2007","journal-title":"J. Acquir. Immune Defic. Syndr"},{"key":"2023072717400733600_bib25","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.advms.2016.09.001","article-title":"Cells of the innate and adaptive immunity and their interactions in inflammatory bowel disease","volume":"62","author":"Kmie\u0107","year":"2017","journal-title":"Adv. Med. Sci"},{"key":"2023072717400733600_bib26","doi-asserted-by":"publisher","first-page":"637","DOI":"10.1084\/jem.20050821","article-title":"Type I interferons act directly on CD8 T cells to allow clonal expansion and memory formation in response to viral infection","volume":"202","author":"Kolumam","year":"2005","journal-title":"J. Exp. Med"},{"key":"2023072717400733600_bib27","doi-asserted-by":"publisher","first-page":"2763","DOI":"10.1182\/blood-2011-02-339515","article-title":"Plasmacytoid dendritic cells are recruited to the colorectum and contribute to immune activation during pathogenic SIV infection in rhesus macaques","volume":"118","author":"Kwa","year":"2011","journal-title":"Blood"},{"key":"2023072717400733600_bib28","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1007\/978-1-61737-979-6_10","article-title":"In vivo depletion of FoxP3+ Tregs using the DEREG mouse model","volume":"707","author":"Lahl","year":"2011","journal-title":"Methods Mol. Biol"},{"key":"2023072717400733600_bib29","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1186\/1743-422X-4-53","article-title":"Clearance of an immunosuppressive virus from the CNS coincides with immune reanimation and diversification","volume":"4","author":"Lauterbach","year":"2007","journal-title":"Virol. J"},{"key":"2023072717400733600_bib30","doi-asserted-by":"publisher","first-page":"4772","DOI":"10.1128\/JVI.02409-10","article-title":"The gut mucosal viral reservoir in HIV-infected patients is not the major source of rebound plasma viremia following interruption of highly active antiretroviral therapy","volume":"85","author":"Lerner","year":"2011","journal-title":"J. Virol"},{"key":"2023072717400733600_bib31","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1016\/j.cell.2015.05.047","article-title":"Data-driven phenotypic dissection of AML reveals progenitor-like cells that correlate with prognosis","volume":"162","author":"Levine","year":"2015","journal-title":"Cell"},{"key":"2023072717400733600_bib32","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1038\/nature22360","article-title":"Stability and function of regulatory T cells expressing the transcription factor T-bet","volume":"546","author":"Levine","year":"2017","journal-title":"Nature"},{"key":"2023072717400733600_bib33","doi-asserted-by":"publisher","first-page":"3271","DOI":"10.1172\/JCI64314","article-title":"Expansion of HIV-specific T follicular helper cells in chronic HIV infection","volume":"122","author":"Lindqvist","year":"2012","journal-title":"J. Clin. Invest"},{"key":"2023072717400733600_bib34","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1038\/nature13475","article-title":"Sphingolipid metabolites in inflammatory disease","volume":"510","author":"Maceyka","year":"2014","journal-title":"Nature"},{"key":"2023072717400733600_bib35","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0061217","article-title":"phyloseq: an R package for reproducible interactive analysis and graphics of microbiome census data","volume":"8","author":"McMurdie","year":"2013","journal-title":"PLoS One"},{"key":"2023072717400733600_bib36","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1016\/j.ejca.2015.11.016","article-title":"Immune-related adverse events with immune checkpoint blockade: a comprehensive review","volume":"54","author":"Michot","year":"2016","journal-title":"Eur. J. Cancer"},{"key":"2023072717400733600_bib37","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1038\/nri2524","article-title":"B cells in HIV infection and disease","volume":"9","author":"Moir","year":"2009","journal-title":"Nat. Rev. Immunol"},{"key":"2023072717400733600_bib38","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1099\/0022-1317-76-2-381","article-title":"Role of virus and host variables in virus persistence or immunopathological disease caused by a non-cytolytic virus","volume":"76","author":"Moskophidis","year":"1995","journal-title":"J. Gen. Virol"},{"key":"2023072717400733600_bib39","doi-asserted-by":"publisher","first-page":"667","DOI":"10.1038\/nri3738","article-title":"Regional specialization within the intestinal immune system","volume":"14","author":"Mowat","year":"2014","journal-title":"Nat. Rev. Immunol"},{"key":"2023072717400733600_bib40","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1038\/nri.2015.3","article-title":"Tissue-resident memory T cells: local specialists in immune defence","volume":"16","author":"Mueller","year":"2016","journal-title":"Nat. Rev. Immunol"},{"key":"2023072717400733600_bib41","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1016\/j.semcancer.2019.05.001","article-title":"Risk of colorectal cancer in inflammatory bowel diseases","volume":"64","author":"Nadeem","year":"2020","journal-title":"Semin. Cancer Biol"},{"key":"2023072717400733600_bib42","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1097\/01.JAA.0000524712.40590.76","article-title":"An introduction to gastrointestinal tract CMV disease","volume":"30","author":"O\u02bcHara","year":"2017","journal-title":"JAAPA"},{"key":"2023072717400733600_bib43","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1016\/j.virol.2010.11.023","article-title":"Decoding arenavirus pathogenesis: essential roles for alpha-dystroglycan-virus interactions and the immune response","volume":"411","author":"Oldstone","year":"2011","journal-title":"Virology"},{"key":"2023072717400733600_bib44","doi-asserted-by":"publisher","first-page":"1220","DOI":"10.1126\/science.1229620","article-title":"Progenitor and terminal subsets of CD8+ T cells cooperate to contain chronic viral infection","volume":"338","author":"Paley","year":"2012","journal-title":"Science"},{"key":"2023072717400733600_bib45","doi-asserted-by":"publisher","first-page":"1905","DOI":"10.1084\/jem.20132577","article-title":"Interplay between regulatory T cells and PD-1 in modulating T cell exhaustion and viral control during chronic LCMV infection","volume":"211","author":"Penaloza-MacMaster","year":"2014","journal-title":"J. Exp. Med"},{"key":"2023072717400733600_bib46","doi-asserted-by":"publisher","first-page":"1641","DOI":"10.1093\/molbev\/msp077","article-title":"FastTree: computing large minimum evolution trees with profiles instead of a distance matrix","volume":"26","author":"Price","year":"2009","journal-title":"Mol. Biol. Evol"},{"key":"2023072717400733600_bib47","doi-asserted-by":"publisher","first-page":"185","DOI":"10.3389\/fmicb.2016.00185","article-title":"Intestinal short chain fatty acids and their link with diet and human health","volume":"7","author":"R\u00edos-Covi\u00e1n","year":"2016","journal-title":"Front. Microbiol"},{"key":"2023072717400733600_bib48","doi-asserted-by":"publisher","DOI":"10.7717\/peerj.2584","article-title":"VSEARCH: a versatile open source tool for metagenomics","volume":"4","author":"Rognes","year":"2016","journal-title":"PeerJ"},{"key":"2023072717400733600_bib49","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1016\/j.coi.2015.03.002","article-title":"New insights into type I interferon and the immunopathogenesis of persistent viral infections","volume":"34","author":"Snell","year":"2015","journal-title":"Curr. Opin. Immunol"},{"key":"2023072717400733600_bib50","doi-asserted-by":"publisher","first-page":"542","DOI":"10.1016\/j.it.2017.05.005","article-title":"Type I interferon in chronic virus infection and cancer","volume":"38","author":"Snell","year":"2017","journal-title":"Trends Immunol"},{"key":"2023072717400733600_bib51","doi-asserted-by":"publisher","first-page":"678","DOI":"10.1016\/j.immuni.2018.08.002","article-title":"CD8+ T cell priming in established chronic viral infection preferentially directs differentiation of memory-like cells for sustained immunity","volume":"49","author":"Snell","year":"2018","journal-title":"Immunity"},{"key":"2023072717400733600_bib52","doi-asserted-by":"publisher","first-page":"501","DOI":"10.1093\/intimm\/dxu052","article-title":"Regulation of intestinal health and disease by innate lymphoid cells","volume":"26","author":"Sonnenberg","year":"2014","journal-title":"Int. Immunol"},{"key":"2023072717400733600_bib53","doi-asserted-by":"publisher","first-page":"737","DOI":"10.1016\/j.cell.2015.03.031","article-title":"Quantifying memory CD8 T cells reveals regionalization of immunosurveillance","volume":"161","author":"Steinert","year":"2015","journal-title":"Cell"},{"key":"2023072717400733600_bib54","doi-asserted-by":"publisher","first-page":"801","DOI":"10.1016\/j.immuni.2014.04.010","article-title":"Bystander chronic infection negatively impacts development of CD8(+) T cell memory","volume":"40","author":"Stelekati","year":"2014","journal-title":"Immunity"},{"key":"2023072717400733600_bib55","doi-asserted-by":"publisher","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":"Subramanian","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2023072717400733600_bib56","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1007183","article-title":"Norovirus interactions with the commensal microbiota","volume":"14","author":"Sullender","year":"2018","journal-title":"PLoS Pathog"},{"key":"2023072717400733600_bib57","doi-asserted-by":"publisher","first-page":"194","DOI":"10.3389\/fimmu.2017.00194","article-title":"CD4 CTL, a cytotoxic subset of CD4+ T cells, their differentiation and function","volume":"8","author":"Takeuchi","year":"2017","journal-title":"Front. Immunol"},{"key":"2023072717400733600_bib58","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1126\/science.1235214","article-title":"Persistent LCMV infection is controlled by blockade of type I interferon signaling","volume":"340","author":"Teijaro","year":"2013","journal-title":"Science"},{"key":"2023072717400733600_bib59","doi-asserted-by":"publisher","first-page":"723","DOI":"10.1016\/j.immuni.2017.09.017","article-title":"Differentiation and protective capacity of virus-specific CD8+ T cells suggest murine norovirus persistence in an immune-privileged enteric niche","volume":"47","author":"Tomov","year":"2017","journal-title":"Immunity"},{"key":"2023072717400733600_bib60","doi-asserted-by":"publisher","first-page":"5261","DOI":"10.1128\/AEM.00062-07","article-title":"Naive Bayesian classifier for rapid assignment of rRNA sequences into the new bacterial taxonomy","volume":"73","author":"Wang","year":"2007","journal-title":"Appl. Environ. Microbiol"},{"key":"2023072717400733600_bib61","doi-asserted-by":"publisher","first-page":"355","DOI":"10.3389\/fimmu.2016.00355","article-title":"Tr1-like T cells \u2014 an enigmatic regulatory T cell lineage","volume":"7","author":"White","year":"2016","journal-title":"Front. Immunol"},{"key":"2023072717400733600_bib62","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1126\/science.1235208","article-title":"Blockade of chronic type I interferon signaling to control persistent LCMV infection","volume":"340","author":"Wilson","year":"2013","journal-title":"Science"},{"key":"2023072717400733600_bib63","doi-asserted-by":"publisher","first-page":"363","DOI":"10.1111\/cei.12884","article-title":"Chronic norovirus infection and common variable immunodeficiency","volume":"188","author":"Woodward","year":"2017","journal-title":"Clin. Exp. Immunol"},{"key":"2023072717400733600_bib64","doi-asserted-by":"publisher","first-page":"260","DOI":"10.1172\/JCI89488","article-title":"Targeting type I interferon-mediated activation restores immune function in chronic HIV infection","volume":"127","author":"Zhen","year":"2017","journal-title":"J. Clin. Invest"}],"container-title":["Journal of Experimental Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/doi\/10.1084\/jem.20191473\/1818392\/jem_20191473.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/doi\/10.1084\/jem.20191473\/1818392\/jem_20191473.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,27]],"date-time":"2023-07-27T13:46:19Z","timestamp":1690465579000},"score":1,"resource":{"primary":{"URL":"https:\/\/rupress.org\/jem\/article\/217\/12\/e20191473\/152068\/A-network-of-immune-and-microbial-modifications"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,3]]},"references-count":64,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2020,12,7]]}},"URL":"https:\/\/doi.org\/10.1084\/jem.20191473","relation":{},"ISSN":["0022-1007","1540-9538"],"issn-type":[{"value":"0022-1007","type":"print"},{"value":"1540-9538","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9,3]]},"article-number":"e20191473"}}