{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T09:56:25Z","timestamp":1790762185363,"version":"4.1.0"},"reference-count":32,"publisher":"American Society for Microbiology","issue":"9","license":[{"start":{"date-parts":[[2018,5,1]],"date-time":"2018-05-01T00:00:00Z","timestamp":1525132800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["P01 AI76174"],"award-info":[{"award-number":["P01 AI76174"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["P51 OD011132"],"award-info":[{"award-number":["P51 OD011132"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["P30 AI050409"],"award-info":[{"award-number":["P30 AI050409"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2018,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Pathogenic human immunodeficiency virus (HIV)\/simian immunodeficiency virus (SIV) infection of humans and rhesus macaques (RMs) induces persistently high production of type I interferon (IFN-I), which is thought to contribute to disease progression. To elucidate the specific role of interferon alpha (IFN-\u03b1) in SIV pathogenesis, 12 RMs were treated prior to intravenous (i.v.) SIV\n            <jats:sub>mac239<\/jats:sub>\n            infection with a high or a low dose of an antibody (AGS-009) that neutralizes most IFN-\u03b1 subtypes and were compared with six mock-infused, SIV-infected controls. Plasma viremia was measured postinfection to assess the effect of IFN-\u03b1 blockade on virus replication, and peripheral blood and lymphoid tissue samples were analyzed by immunophenotypic staining. Consistent with the known antiviral effect of IFN-I, high-dose AGS-009 treatment induced a modest increase in acute-phase viral loads versus controls. Four out of 6 RMs receiving a high dose of AGS-009 also experienced an early decline in CD4\n            <jats:sup>+<\/jats:sup>\n            T cell counts that was associated with progression to AIDS. Interestingly, 50% of the animals treated with AGS-009 (6\/12) developed AIDS within 1 year of infection compared with 17% (1\/6) of untreated controls. Finally, blockade of IFN-\u03b1 decreased the levels of activated CD4\n            <jats:sup>+<\/jats:sup>\n            and CD8\n            <jats:sup>+<\/jats:sup>\n            T cells, as well as B cells, as measured by PD-1 and\/or Ki67 expression. The lower levels of activated lymphocytes in IFN-\u03b1-blockaded animals supports the hypothesis that IFN-\u03b1 signaling contributes to lymphocyte activation during SIV infection and suggests that this signaling pathway is involved in controlling virus replication during acute infection. The potential anti-inflammatory effect of IFN-\u03b1 blockade should be explored as a strategy to reduce immune activation in HIV-infected individuals.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            Interferon alpha (IFN-\u03b1) is a member of a family of molecules (type I interferons) that prevent or limit virus infections in mammals. However, IFN-\u03b1 production may contribute to the chronic immune activation that is thought to be the primary cause of immune decline and AIDS in HIV-infected patients. The study presented here attempts to understand the contribution of IFN-\u03b1 to the natural history and progression of SIV infection of rhesus macaques, the primary nonhuman primate model system for testing hypotheses about HIV infection in humans. Here, we show that blockade of IFN-\u03b1 action promotes lower chronic immune activation but higher early viral loads, with a trend toward faster disease progression. This study has significant implications for new treatments designed to impact the type I interferon system.\n          <\/jats:p>","DOI":"10.1128\/jvi.01760-17","type":"journal-article","created":{"date-parts":[[2018,2,19]],"date-time":"2018-02-19T14:30:32Z","timestamp":1519050632000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":27,"title":["Reduced Chronic Lymphocyte Activation following Interferon Alpha Blockade during the Acute Phase of Simian Immunodeficiency Virus Infection in Rhesus Macaques"],"prefix":"10.1128","volume":"92","author":[{"given":"Diane","family":"Carnathan","sequence":"first","affiliation":[{"name":"Emory Vaccine Center and Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benton","family":"Lawson","sequence":"additional","affiliation":[{"name":"Emory Vaccine Center and Yerkes National Primate 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