In vivo characterization of macrophage-tropic simian immunodeficiency virus molecular clones in rhesus macaques

• Type of Material: Article
• Authors: Sanjeev Gumber, Emory University; Praveen Kumar Amancha, University of Louisiana; Po-Jen Yen, Dana-Farber Cancer Institute; Francois Villinger, Emory University; Dana Gabuzda, Dana-Farber Cancer Institute; Siddappa Byrareddy, Emory University
• Language: English
• Date: 2018-08-01
• Publisher: Taylor & Francis: STM, Behavioural Science and Public Health Titles
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2018, Journal of NeuroVirology, Inc.
• Final Published Version (URL): http://dx.doi.org/10.1007/s13365-018-0628-2
• Title of Journal or Parent Work: Journal of NeuroVirology
• ISSN: 1355-0284
• Volume: 24
• Issue: 4
• Start Page: 411
• End Page: 419
• Grant/Funding Information: This study was supported in part by NIH R01AI113883 & R21AI114415 to SNB.; DG was supported by NIH R01 MH 97659.
• Keywords: Myeloid cells; Science & Technology; REPLICATION; Central nerveous system; Macrophages; SIV; CD4 EXPRESSION; TYPE-1; Neurosciences & Neurology; RETROVIRUS; Neurosciences; Macrophage-tropic; PERIVASCULAR MACROPHAGES; INFECTION; Life Sciences & Biomedicine; IDENTIFICATION; HIV-1; CEREBROSPINAL-FLUID; Rhesus macaques; Virology; VIRAL LOAD
• Research Categories: Biology, Animal Physiology; Health Sciences, Immunology; Biology, Microbiology

Abstract

Macrophages are a major target of HIV/SIV infection and play an important role in pathogenesis by serving as viral reservoirs in the central nervous system. Previously, a unique early SIVmac251 envelope (Env) variant, deSIV147 was cloned from blood of a rhesus macaque with rapid disease progression and SIV-associated encephalitis. Here, we show that infectious molecular clone deSIV147 caused systemic infection in rhesus macaques following intravenous or intrarectal exposure. Next, we inoculated deSIV147 into macaques depleted of CD4+ T cells and found that animals were SIV-positive, with high plasma and CSF viral loads. These macaques also showed SIVp17-positive macrophages in brain, lymph nodes, colon, lung, and liver. Furthermore, accumulation of perivascular macrophages, multinucleated giant cells, and microgliosis was detected. These findings suggest that the neurotropic deSIV147 clone will be useful to study macrophage infection in HIV/SIV-associated neurocognitive disorders, gain insights into myeloid cell reservoirs in brain and other anatomical sites, as well as test strategies for eradication.