Vpr R77Q is associated with long-term nonprogressive HIV infection and impaired induction of apoptosis

Julian J. Lum, Oren J. Cohen, Zilin Nie, Joel G. Weaver, Timothy S. Gomez, Xiao Jian Yao, David Lynch, André A. Pilon, Nanci Hawley, John E. Kim, Zhaoxia Chen, Michael Montpetit, Jaime Sanchez-Dardon, Eric A. Cohen, Andrew David Badley

Research output: Contribution to journalArticle

Abstract

The absence of immune defects that occurs in the syndrome of long-term nonprogressive (LTNP) HIV infection offers insights into the pathophysiology of HIV-induced immune disease. The (H[F/S]RIG)2 domain of viral protein R (Vpr) induces apoptosis and may contribute to HIV-induced T cell depletion. We demonstrate a higher frequency of R77Q Vpr mutations in patients with LTNP than in patients with progressive disease. In addition, T cell infections using vesicular stomatitis virus G (VSV-G) pseudotyped HIV-1 Vpr R77Q result in less (P = 0.01) T cell death than infections using wild-type Vpr, despite similar levels of viral replication. Wild-type Vpr-associated events, including procaspase-8 and -3 cleavage, loss of mitochondrial transmembrane potential (ΔΨm), and DNA fragmentation factor activation are attenuated by R77Q Vpr. These data highlight the pathophysiologic role of Vpr in HIV-induced immune disease and suggest a novel mechanism of LTNP.

Original languageEnglish (US)
Pages (from-to)1547-1554
Number of pages8
JournalJournal of Clinical Investigation
Volume111
Issue number10
DOIs
StatePublished - May 2003

ASJC Scopus subject areas

  • Medicine(all)

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    Lum, J. J., Cohen, O. J., Nie, Z., Weaver, J. G., Gomez, T. S., Yao, X. J., Lynch, D., Pilon, A. A., Hawley, N., Kim, J. E., Chen, Z., Montpetit, M., Sanchez-Dardon, J., Cohen, E. A., & Badley, A. D. (2003). Vpr R77Q is associated with long-term nonprogressive HIV infection and impaired induction of apoptosis. Journal of Clinical Investigation, 111(10), 1547-1554. https://doi.org/10.1172/JCI200316233