Transmitted/founder SHIV.D replicates in the brain, causes neuropathogenesis, and persists on combination antiretroviral therapy in rhesus macaques

Retrovirology

Brief Report

Huaqing Zhao¹  Rachel M. Podgorski²  Mandy D. Smith²  Tricia H. Burdo²  Jake A. Robinson²  Suvadip Mallick³  Katharine J. Bar³  Dennis L. Kolson⁴  Ronald S. Veazey⁵ 

[1]Center for Biostatistics and Epidemiology, Department of Biomedical Education and Data Science, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA

[2]Center for NeuroVirology and Gene Editing, Department of Microbiology, Immunology, and Inflammation, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA

[3]Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

[4]Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

[5]Tulane National Primate Research Center, Tulane School of Medicine, Covington, LA, USA

关键词: SHIV;    Non-human primates;    HIV;    Persistence;    NeuroHIV;   

DOI  :  10.1186/s12977-023-00628-5

 received in 2023-03-27, accepted in 2023-07-11,  发布年份 2023

来源: Springer

【 摘 要 】

A biologically relevant non-human primate (NHP) model of HIV persistence in the central nervous system (CNS) is necessary. Most current NHP/SIV models of HIV infection fail to recapitulate viral persistence in the CNS without encephalitis or fail to employ viruses that authentically represent the ongoing HIV-1 pandemic. Here, we demonstrate viral replication in the brain and neuropathogenesis after combination antiretroviral therapy (ART) in rhesus macaques (RMs) using novel macrophage-tropic transmitted/founder (TF) simian-human immunodeficiency virus SHIV.D.191,859 (SHIV.D). Quantitative immunohistochemistry (IHC) and DNA/RNAscope in situ hybridization (ISH) were performed on three brain regions from six SHIV.D-infected RMs; two necropsied while viremic, two during analytical treatment interruptions, and two on suppressive ART. We demonstrated myeloid-mediated neuroinflammation, viral replication, and proviral DNA in the brain in all animals. These results demonstrate that TF SHIV.D models native HIV-1 CNS replication, pathogenesis, and persistence on ART in rhesus macaques.

【 授权许可】

CC BY   
© Diane D. Jeang 2023

【 图 表 】

12938_2023_1137_Article_IEq32.gif

Fig. 3

Fig. 1