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.
View: Text | PDF
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

×

Figure 1

Options: View larger image (or click on image) Download as PowerPoint
R77Q Vpr induces less apoptosis in single-cycle infections using VSV-G p...
R77Q Vpr induces less apoptosis in single-cycle infections using VSV-G pseudotype HIV-1 virus. (a) Jurkat T cells were infected at an MOI of 0.01 with VSV-G pseudotyped virus expressing wild-type Vpr, Vpr-negative (Vpr–), or R77Q Vpr. Cells were analyzed by annexin V FITC/propidium iodide (PI) staining for apoptotic cells at the indicated time points after infection. Values are representative of three independent experiments. The inset denotes the number of propidium iodide–positive cells at each time point (% annextin+/PI– refers to the percentage of cells which stain with annexin V-FITC, but not PI). (b) Cells were isolated on day 6 after infection and stained with TUNEL for apoptosis measurement and with p24 antibody for measurement of viral replication. Data are representative of two independent infections.