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

Autor: Rachel M. Podgorski, Jake A. Robinson, Mandy D. Smith, Suvadip Mallick, Huaqing Zhao, Ronald S. Veazey, Dennis L. Kolson, Katharine J. Bar, Tricia H. Burdo
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Retrovirology, Vol 20, Iss 1, Pp 1-10 (2023)
Druh dokumentu: article
ISSN: 1742-4690
DOI: 10.1186/s12977-023-00628-5
Popis: Abstract 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.
Databáze: Directory of Open Access Journals
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