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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Figure 9

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Effects of wild-type or R77Q Vpr on T cell depletion in vivo. Balb-c mic...
Effects of wild-type or R77Q Vpr on T cell depletion in vivo. Balb-c mice (21–28 days old) were intravenously injected with vehicle control alone (data not shown) or vehicle containing wild-type Vpr or mutant Vpr. The absolute CD4+ or CD8+ T cell number at baseline, 24, and 48 hours after injection was determined by FACS analysis. Data are presented as the percent decrease from baseline normalized to control mice for CD4+ T cells (a) or CD8+ T cells (b).