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 D. Badley
J Clin Invest.
2003;
111(10):1547–1554
doi:10.1172/JCI16233
This article Copyright © 2003, The American Society for Clinical Investigation
Abstract
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T
he 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.
