Both brain macrophages and memory CD4+ T-cells may serve as potential reservoirs in SIV-infected rhesus macaques

Authors

• CA Lee
• E Beasley
• K Sundar
• K Matsuda
• F Wu
• CL Vinton
• C Deleage
• MG Smelkinson
• JD Estes
• JM Brenchley
• VM Hirsch

Abstract

Human immunodeficiency virus (HIV) infects the central nervous system (CNS) early in the course of disease, which can lead to HIV-induced encephalitis (HIVE/neuroAIDS). Simian-immunodeficiency virus (SIV) infected non-human primates serve as a relevant model for neuroAIDS with pathologic and clinical features reminiscent of HIVE. In a recent study, we isolated a neuropathogenic clone SIVsm804E-CL757 (CL757) from rhesus macaques following four in vivo serial passages. This virus induces SIVE in 50% of the animals with high CSF viral loads and the formation of lesions in the. The aim of this current study was to isolate and identify cellular subsets in the brain that can serve as potential viral reservoirs. Isolation of mononuclear cells from the brains of SIV infected macaques showed that CSF viral load correlated with an increase in the number of mononuclear cells, specifically brain CD4+ memory T cells (mCD4s) and macrophages (MFs), indicating cell infiltration in the brains of animals with SIVE. Using cell sorting and SIV qPCR we show that both mCD4s and MFs harbor viral DNA and corroborated in situ using DNAscope. Virus isolation by co-culturing techniques confirmed productive infection of both cell types. Only in animals exhibiting SIVE/neuroAIDS was SIV DNA detected in MFs. Phylogenetic analysis using gp120 sequences show that SIV variants in MFs and mCD4s are compartmentalized with sequences from the CSF and distinct from sequences in the blood mCD4 cells indicating viral replication within each cellular subset which suggests a previously unanticipated role of mCD4s as a potential reservoir in the brain.

Scientific Focus Area: Virology

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