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

Journal of Virology
Diane CarnathanThomas H Vanderford

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.) SIVmac239 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 level...Continue Reading

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Citations

Jul 13, 2018·AIDS Research and Human Retroviruses·Sho SugawaraAshwin Balagopal
Feb 15, 2019·Virologica Sinica·Krystelle Nganou-Makamdop, Daniel C Douek
Aug 20, 2019·The Journal of Experimental Medicine·Franck J Barrat, Lishan Su
Jun 4, 2019·Frontiers in Immunology·Jake William RhodesStuart Grant Turville
Oct 17, 2019·Frontiers in Immunology·Kirstie Melissa BertramAndrew Nicholas Harman
Jun 30, 2021·The Journal of Immunology : Official Journal of the American Association of Immunologists·Stéphane IsnardAnne Hosmalin

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