Identification and characterization of a macrophage-tropic SIV envelope glycoprotein variant in blood from early infection in SIVmac251-infected macaques

Po Jen Yen, Megan E. Mefford, James A. Hoxie, Kenneth C. Williams, Ronald Charles Desrosiers, Dana Gabuzda

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Macrophages play an important role in HIV/SIV pathogenesis by serving as a reservoir for viral persistence in brain and other tissues. Infected macrophages have been detected in brain early after infection, but macrophage-tropic viruses are rarely isolated until late-stage infection. Little is known about early variants that establish persistent infection in brain. Here, we characterize a unique macrophage-tropic SIV envelope glycoprotein (Env) variant from two weeks post-infection in blood of an SIVmac251-infected macaque that is closely related to sequences in brain from animals with neurological disease. SIVmac251 clones expressing this Env are highly fusogenic, and replicate efficiently in T cells and macrophages. N173 and N481 were identified as novel determinants of macrophage tropism and neutralization sensitivity. These results imply that macrophage-tropic SIV capable of establishing viral reservoirs in brain can be present in blood during early infection. Furthermore, these SIVmac251 clones will be useful for studies on pathogenesis, eradication, and vaccines.

Original languageEnglish (US)
Pages (from-to)53-68
Number of pages16
JournalVirology
Volume458-459
Issue number1
DOIs
StatePublished - 2014
Externally publishedYes

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Keywords

  • Brain
  • Envelope glycoprotein (Env)
  • Human immunodeficiency virus (HIV)
  • Macrophage tropism
  • Simian immunodeficiency virus (SIV)

ASJC Scopus subject areas

  • Virology

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