Central nervous system inflammation and infection during early, nonaccelerated simian-human immunodeficiency virus infection in rhesus macaques

Denise C. Hsu, Piyanate Sunyakumthorn, Matthew Wegner, Alexandra Schuetz, Decha Silsorn, Jacob D. Estes, Claire Deleage, Khamis Tomusange, Samir K. Lakhashe, Ruth M. Ruprecht, Eric Lombardini, Rawiwan Im-Erbsin, Yanin Kuncharin, Yuwadee Phuang-Ngern, Dutsadee Inthawong, Weerawan Chuenarom, Robin Burke, Merlin L. Robb, Lishomwa C. Ndhlovu, Jintanat AnanworanichVictor Valcour, Robert J. O'Connell, Serena Spudich, Nelson L. Michael, Sandhya Vasan*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

36 Scopus citations


Studies utilizing highly pathogenic simian immunodeficiency virus (SIV) and simian-human immunodeficiency virus (SHIV) have largely focused on the immunopathology of the central nervous system (CNS) during end-stage neurological AIDS and SIV encephalitis. However, this may not model pathophysiology in earlier stages of infection. In this nonaccelerated SHIV model, plasma SHIV RNA levels and peripheral blood and colonic CD4+ T cell counts mirrored early human immunodeficiency virus (HIV) infection in humans. At 12 weeks postinfection, cerebrospinal fluid (CSF) detection of SHIV RNA and elevations in IP-10 and MCP-1 reflected a discrete neurovirologic process. Immunohistochemical staining revealed a diffuse, low-level CD3+ CD4- cellular infiltrate in the brain parenchyma without a concomitant increase in CD68/CD163+ monocytes, macrophages, and activated microglial cells. Rare SHIV-infected cells in the brain parenchyma and meninges were identified by RNAScope in situ hybridization. In the meninges, there was also a trend toward increased CD4+ infiltration in SHIV-infected animals but no differences in CD68/ CD163+ cells between SHIV-infected and uninfected control animals. These data suggest that in a model that closely recapitulates human disease, CNS inflammation and SHIV in CSF are predominantly mediated by T cell-mediated processes during early infection in both brain parenchyma and meninges. Because SHIV expresses an HIV rather than SIV envelope, this model could inform studies to understand potential HIV cure strategies targeting the HIV envelope.

Original languageEnglish
Article numbere00222-18
JournalJournal of Virology
Issue number11
StatePublished - 1 Jun 2018
Externally publishedYes


  • Early infection
  • HIV
  • Neuropathology
  • SHIV


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