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

Sanjeev Gumber, Praveen Kumar Amancha, Po Jen Yen, Francois Villinger, Dana Gabuzda, Siddappa N. Byrareddy

Research output: Contribution to journalArticle

1 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)411-419
Number of pages9
JournalJournal of neurovirology
Volume24
Issue number4
DOIs
StatePublished - Aug 1 2018

Keywords

  • Central nerveous system
  • Macrophage-tropic
  • Macrophages
  • Myeloid cells
  • Rhesus macaques
  • SIV

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience
  • Virology

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