Reduced Chronic Lymphocyte Activation following Interferon Alpha Blockade during the Acute Phase of Simian Immunodeficiency Virus Infection in Rhesus Macaques

作者：Diane G. Carnathan, Benton Lawson, Joana Yu, Kalpana Patel, James M. Billingsley, Gregory K. Tharp, Olivia M. Delmas, Reem Dawoud, Peter Wilkinson, Charles A. Nicolette, Mark J. Cameron, Rafick‐Pierre Sékaly, Steven E. Bosinger, Guido Silvestri, Thomas H. Vanderford · 发表于：Journal of Virology · 年份：2018 · DOI：10.1128/jvi.01760-17 · 被引用次数：27 · 研究领域：HIV Research and Treatment、Immune Cell Function and Interaction、HIV/AIDS Research and Interventions

ABSTRACT 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-α) in SIV pathogenesis, 12 RMs were treated prior to intravenous (i.v.) SIV mac239 infection with a high or a low dose of an antibody (AGS-009) that neutralizes most IFN-α subtypes and were compared with six mock-infused, SIV-infected controls. Plasma viremia was measured postinfection to assess the effect of IFN-α 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 + 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-α decreased the levels of activated CD4 + and CD8 + T cells, as well as B cells, as measured by PD-1 and/or Ki67 expression. The lower levels of activated lymphocytes in IFN-α-blockaded animals supports the hypothesis that IFN-α signaling contributes to lymphocyt...