{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T19:00:21Z","timestamp":1791313221527,"version":"4.3.1"},"reference-count":54,"publisher":"American Society for Microbiology","issue":"8","license":[{"start":{"date-parts":[[2014,4,15]],"date-time":"2014-04-15T00:00:00Z","timestamp":1397520000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2014,4,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            The antiviral role of TRIM E3 ligases\n            <jats:italic>in vivo<\/jats:italic>\n            is not fully understood. To test the hypothesis that TRIM5\u03b1 and TRIM22 have differential transcriptional regulation and distinct anti-HIV roles according to infection phase and compartment, we measured TRIM5\u03b1, TRIM22, and type I interferon (IFN-I)-inducible myxovirus resistance protein A (MxA) levels in peripheral blood mononuclear cells (PBMCs) during primary and chronic HIV-1 infection, with chronic infection samples being matched PBMCs and central nervous system (CNS)-derived cells. Associations with biomarkers of disease progression were explored. The impact of IFN-I, select proinflammatory cytokines, and HIV on TRIM E3 ligase-specific expression was investigated. PBMCs from individuals with primary and chronic HIV-1 infection had significantly higher levels of MxA and TRIM22 than did PBMCs from HIV-1-negative individuals (\n            <jats:italic>P<\/jats:italic>\n            &lt; 0.05 for all comparisons). PBMCs from chronic infection had lower levels of TRIM5\u03b1 than did PBMCs from primary infection or HIV-1-uninfected PBMCs (\n            <jats:italic>P<\/jats:italic>\n            = 0.0001 for both). In matched CNS-derived samples and PBMCs, higher levels of MxA (\n            <jats:italic>P<\/jats:italic>\n            = 0.001) and TRIM5\u03b1 (\n            <jats:italic>P<\/jats:italic>\n            = 0.0001) in the CNS were noted. There was a negative correlation between TRIM22 levels in PBMCs and plasma viral load (\n            <jats:italic>r<\/jats:italic>\n            = \u22120.40;\n            <jats:italic>P<\/jats:italic>\n            = 0.04).\n            <jats:italic>In vitro<\/jats:italic>\n            , IFN-I and, rarely, proinflammatory cytokines induced TRIM5\u03b1 and TRIM22 in a cell type-dependent manner, and the knockdown of either protein in CD4\n            <jats:sup>+<\/jats:sup>\n            lymphocytes resulted in increased HIV-1 infection. These data suggest that there are infection-phase-specific and anatomically compartmentalized differences in TRIM5\u03b1 and TRIM22 regulation involving primarily IFN-I and specific cell types and indicate subtle differences in the antiviral roles and transcriptional regulation of TRIM E3 ligases\n            <jats:italic>in vivo<\/jats:italic>\n            .\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            Type I interferon-inducible TRIM E3 ligases are a family of intracellular proteins with potent antiviral activities mediated through diverse mechanisms. However, little is known about the contribution of these proteins to antiviral immunity\n            <jats:italic>in vivo<\/jats:italic>\n            and how their expression is regulated. We show here that TRIM5\u03b1 and TRIM22, two prominent members of the family, have different expression patterns\n            <jats:italic>in vivo<\/jats:italic>\n            and that the expression pattern depends on HIV-1 infection status and phase. Furthermore, expression differs in peripheral blood versus central nervous system anatomical sites of infection. Only TRIM22 expression correlated negatively with HIV-1 viral load, but gene silencing of both proteins enhances HIV-1 infection of target cells. We report subtle differences in TRIM5\u03b1 and TRIM22 gene induction by IFN-I and proinflammatory cytokines in CD4\n            <jats:sup>+<\/jats:sup>\n            lymphocytes, monocytes, and neuronal cells. This study enhances our understanding of antiviral immunity by intrinsic antiviral factors and how their expression is determined.\n          <\/jats:p>","DOI":"10.1128\/jvi.03603-13","type":"journal-article","created":{"date-parts":[[2014,1,30]],"date-time":"2014-01-30T04:17:19Z","timestamp":1391055439000},"page":"4291-4303","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":23,"title":["TRIM5\u03b1 and TRIM22 Are Differentially Regulated According to HIV-1 Infection Phase and Compartment"],"prefix":"10.1128","volume":"88","author":[{"given":"Ravesh","family":"Singh","sequence":"first","affiliation":[{"name":"KwaZulu-Natal Research Institute for Tuberculosis and HIV (K-RITH), Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa"},{"name":"HIV Pathogenesis Programme, Doris Duke Medical Research Institute, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vinod","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of KwaZulu-Natal, Durban, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianne W.","family":"Mureithi","sequence":"additional","affiliation":[{"name":"KwaZulu-Natal Research Institute for Tuberculosis and HIV (K-RITH), Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa"},{"name":"HIV Pathogenesis Programme, Doris Duke Medical Research Institute, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa"},{"name":"The Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivek","family":"Naranbhai","sequence":"additional","affiliation":[{"name":"HIV Pathogenesis Programme, Doris Duke Medical Research Institute, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa"},{"name":"Centre for the AIDS Programme of Research in South Africa (CAPRISA), Doris Duke Medical Research Institute, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Duran","family":"Ramsuran","sequence":"additional","affiliation":[{"name":"KwaZulu-Natal Research Institute for Tuberculosis and HIV (K-RITH), Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sahil","family":"Tulsi","sequence":"additional","affiliation":[{"name":"HIV Pathogenesis Programme, Doris Duke Medical Research Institute, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa"},{"name":"Centre for the AIDS Programme of Research in South Africa (CAPRISA), Doris Duke Medical Research Institute, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keshni","family":"Hiramen","sequence":"additional","affiliation":[{"name":"KwaZulu-Natal Research Institute for Tuberculosis and HIV (K-RITH), Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa"},{"name":"HIV Pathogenesis Programme, Doris Duke Medical Research Institute, Nelson R. 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