Vpr R77Q is Associated with Long-term Nonprogressive HIV Infection and Impaired Induction of Apoptosis

Overview

Journal J Clin Invest

Specialty General Medicine

Date 2003 May 17

PMID 12750404

Citations 92

Authors

Julian J Lum

Oren J Cohen

Zilin Nie

Joel G Weaver

Timothy S Gomez

Xiao-Jian Yao

David Lynch

Andre A Pilon

Nanci Hawley

John E Kim

Zhaoxia Chen

Michael Montpetit

Jaime Sanchez-Dardon

Eric A Cohen

Andrew D Badley

Affiliations

Soon will be listed here.

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 (deltapsi(m)), 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.

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