{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T08:53:32Z","timestamp":1785920012736,"version":"3.56.0"},"reference-count":149,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2021,9,29]],"date-time":"2021-09-29T00:00:00Z","timestamp":1632873600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01AI153076"],"award-info":[{"award-number":["R01AI153076"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01AI162631"],"award-info":[{"award-number":["R01AI162631"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Ever since the immune regulatory strains of lymphocytic choriomeningitis virus (LCMV), such as Clone 13, were isolated, LCMV infection of mice has served as a valuable model for the mechanistic study of viral immune suppression and virus persistence. The exhaustion of virus-specific T cells was demonstrated during LCMV infection, and the underlying mechanisms have been extensively investigated using LCMV infection in mouse models. In particular, the mechanism for gradual CD8+ T cell exhaustion at molecular and transcriptional levels has been investigated. These studies revealed crucial roles for inhibitory receptors, surface markers, regulatory cytokines, and transcription factors, including PD-1, PSGL-1, CXCR5, and TOX in the regulation of T cells. However, the action mode for CD4+ T cell suppression is largely unknown. Recently, sphingosine kinase 2 was proven to specifically repress CD4+ T cell proliferation and lead to LCMV persistence. As CD4+ T cell regulation was also known to be important for viral persistence, research to uncover the mechanism for CD4+ T cell repression could help us better understand how viruses launch and prolong their persistence. This review summarizes discoveries derived from the study of LCMV in regard to the mechanisms for T cell suppression and approaches for the termination of viral persistence with special emphasis on CD8+ T cells.<\/jats:p>","DOI":"10.3390\/v13101951","type":"journal-article","created":{"date-parts":[[2021,10,11]],"date-time":"2021-10-11T01:59:47Z","timestamp":1633917587000},"page":"1951","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Chronic LCMV Infection Is Fortified with Versatile Tactics to Suppress Host T Cell Immunity and Establish Viral Persistence"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3795-0774","authenticated-orcid":false,"given":"Caleb J.","family":"Studstill","sequence":"first","affiliation":[{"name":"Departments of Surgery and Molecular Microbiology & Immunology, University of Missouri-Columbia, Medical Science Building M331, One Hospital Drive, Columbia, MO 65212, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0083-6129","authenticated-orcid":false,"given":"Bumsuk","family":"Hahm","sequence":"additional","affiliation":[{"name":"Departments of Surgery and Molecular Microbiology & Immunology, University of Missouri-Columbia, Medical Science Building M331, One Hospital Drive, Columbia, MO 65212, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1128\/iai.4.3.281-286.1971","article-title":"Lytic and Turbid Plaque-Type Mutants of Lymphocytic Choriomeningitis Virus as a Cause of Neurological Disease or Persistent Infection","volume":"4","author":"Hotchin","year":"1971","journal-title":"Infect. 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