Vpr R77Q is associated with long-term nonprogressive HIV infection and impaired induction of apoptosis
Julian J. Lum, … , Eric A. Cohen, Andrew D. Badley
Julian J. Lum, … , Eric A. Cohen, Andrew D. Badley
Published May 15, 2003
Citation Information: J Clin Invest. 2003;111(10):1547-1554. https://doi.org/10.1172/JCI16233.
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Article Immunology

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

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.

Authors

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

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Vpr R77Q induces less apoptosis than wild-type Vpr. Jurkat cells were tr...
Vpr R77Q induces less apoptosis than wild-type Vpr. Jurkat cells were treated with synthetic C-terminal wild-type or R77Q Vpr peptides for 16 hours followed by annexin V FITC/propidium iodide staining. Data represent the average of three independent experiments. The inset denotes the number of propidium iodide–positive cells at each time point.