{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T11:30:26Z","timestamp":1761823826933,"version":"3.37.3"},"reference-count":62,"publisher":"American Society for Microbiology","issue":"22","license":[{"start":{"date-parts":[[2016,11,15]],"date-time":"2016-11-15T00:00:00Z","timestamp":1479168000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100008880","name":"KANAE Foundation for the Promotion of Medical Science","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100008880","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI047140","AI077719"],"award-info":[{"award-number":["AI047140","AI077719"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005927","name":"Daiichi Sankyo Foundation of Life Science","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005927","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2016,11,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Several arenaviruses, chiefly Lassa virus (LASV), cause hemorrhagic fever disease in humans and pose serious public health concerns in their regions of endemicity. Moreover, mounting evidence indicates that the worldwide-distributed prototypic arenavirus, lymphocytic choriomeningitis virus (LCMV), is a neglected human pathogen of clinical significance. We have documented that a recombinant LCMV containing the glycoprotein (GPC) gene of LASV within the backbone of the immunosuppressive clone 13 (Cl-13) variant of the Armstrong strain of LCMV (rCl-13\/LASV-GPC) exhibited Cl-13-like growth properties in cultured cells, but in contrast to Cl-13, rCl-13\/LASV-GPC was unable to establish persistence in immunocompetent adult mice, which prevented its use for some\n            <jats:italic>in vivo<\/jats:italic>\n            experiments. Recently, V459K and K461G mutations within the GP2 cytoplasmic domain (CD) of rCl-13\/LASV-GPC were shown to increase rCl-13\/LASV-GPC infectivity in mice. Here, we generated rCl-13(GPC\/VGKS) by introducing the corresponding revertant mutations K465V and G467K within GP2 of rCl-13 and we show that rCl-13(GPC\/VGKS) was unable to persist in mice. K465V and G467K mutations did not affect GPC processing, virus RNA replication, or gene expression. In addition, rCl-13(GPC\/VGKS) grew to high titers in cultured cell lines and in immunodeficient mice. Further analysis revealed that rCl-13(GPC\/VGKS) infected fewer splenic plasmacytoid dendritic cells than rCl-13, yet the two viruses induced similar type I interferon responses in mice. Our findings have identified novel viral determinants of Cl-13 persistence and also revealed that virus GPC-host interactions yet to be elucidated critically contribute to Cl-13 persistence.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            The prototypic arenavirus, lymphocytic choriomeningitis virus (LCMV), provides investigators with a superb experimental model system to investigate virus-host interactions. The Armstrong strain (ARM) of LCMV causes an acute infection, whereas its derivative, clone 13 (Cl-13), causes a persistent infection. Mutations F260L and K1079Q within GP1 and L polymerase, respectively, have been shown to play critical roles in Cl-13's ability to persist in mice. However, there is an overall lack of knowledge about other viral determinants required for Cl-13's persistence. Here, we report that mutations K465V and G467K within the cytoplasmic domain of Cl-13 GP2 resulted in a virus, rCl-13(GPC\/VGKS), that failed to persist in mice despite exhibiting Cl-13 wild-type-like fitness in cultured cells and immunocompromised mice. This finding has uncovered novel viral determinants of viral persistence, and a detailed characterization of rCl-13(GPC\/VGKS) can provide novel insights into the mechanisms underlying persistent viral infection.\n          <\/jats:p>","DOI":"10.1128\/jvi.01303-16","type":"journal-article","created":{"date-parts":[[2016,9,1]],"date-time":"2016-09-01T00:21:41Z","timestamp":1472689301000},"page":"10102-10112","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":4,"title":["Residues K465 and G467 within the Cytoplasmic Domain of GP2 Play a Critical Role in the Persistence of Lymphocytic Choriomeningitis Virus in Mice"],"prefix":"10.1128","volume":"90","author":[{"given":"Masaharu","family":"Iwasaki","sequence":"first","affiliation":[{"name":"Department of Immunology and Microbial Science, Scripps Research Institute, La Jolla, California, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cherie T.","family":"Ng","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbial Science, Scripps Research Institute, La Jolla, California, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beatrice","family":"Cubitt","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbial Science, Scripps Research Institute, La Jolla, California, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan C.","family":"de la Torre","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbial Science, Scripps Research Institute, La Jolla, California, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","first-page":"1791","volume-title":"Fields virology","author":"Buchmeier MJ","year":"2007","unstructured":"Buchmeier MJ, Peters CJ, de la Torre JC. 2007. Arenaviridae: the viruses and their replication, p 1791\u20131851. In Knipe DM, Howley PM, Griffin DE, Lamb RA, Martin MA, Roizman B, Straus SE (ed), Fields virology, 5th ed, vol 2. Lippincott Williams & Wilkins, Philadelphia, PA.","edition":"5"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2133782100"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.77.19.10700-10705.2003"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2005.05.001"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1142"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.327.7426.1271"},{"key":"e_1_3_3_8_2","first-page":"865","article-title":"Emerging infectious diseases and risk to the traveler","volume":"83","author":"Freedman DO","year":"1999","unstructured":"Freedman DO, Woodall J. 1999. Emerging infectious diseases and risk to the traveler. 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