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Identification and Molecular Characterization of SIV Vpr R50G Mutation Associated with Long Term Survival in SIV-infected Morphine Dependent and Control Macaques

Overview
Journal Virology
Specialty Microbiology
Date 2013 Oct 1
PMID 24074576
Citations 3
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Abstract

Viral protein R (Vpr) is an accessory protein of HIV and SIV involved in the pathogenesis of viral infection. In this study, we monitored SIV evolution in the central nervous system and other organs from morphine-dependent and control animals by sequencing vpr in an attempt to understand the relationship between drug abuse, disease progression, and compartmentalization of viral evolution. Animals in the morphine group developed accelerated disease and died within twenty weeks post-infection. A unique mutation, R50G, was identified in the macaques that survived regardless of morphine exposure. Functional studies revealed that the R50G mutation exhibited altered cellular localization and decreased the expression levels of both IL-6 and IL-8. Our results, therefore, suggest that sequence changes within the SIV/17E-Fr vpr occur regardless of drug abuse but correlate with survival, and that they alter disease progression rates by affecting Vpr functions.

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References
1.
Kumar R, Orsoni S, Norman L, Verma A, Tirado G, Giavedoni L . Chronic morphine exposure causes pronounced virus replication in cerebral compartment and accelerated onset of AIDS in SIV/SHIV-infected Indian rhesus macaques. Virology. 2006; 354(1):192-206. DOI: 10.1016/j.virol.2006.06.020. View

2.
Tungaturthi P, Sawaya B, Ayyavoo V, Murali R, Srinivasan A . HIV-1 Vpr: genetic diversity and functional features from the perspective of structure. DNA Cell Biol. 2004; 23(4):207-22. DOI: 10.1089/104454904773819798. View

3.
Noel R, Toro-Bahamonde A, Marrero-Otero Z, Orsini S, Verma A, Kumar R . Lack of correlation between SIV-Nef evolution and rapid disease progression in morphine-dependent nonhuman primate model of AIDS. AIDS Res Hum Retroviruses. 2006; 22(8):817-23. PMC: 2761833. DOI: 10.1089/aid.2006.22.817. View

4.
Le Rouzic E, Benichou S . The Vpr protein from HIV-1: distinct roles along the viral life cycle. Retrovirology. 2005; 2:11. PMC: 554975. DOI: 10.1186/1742-4690-2-11. View

5.
Shah A, Verma A, Patel K, Noel R, Rivera-Amill V, Silverstein P . HIV-1 gp120 induces expression of IL-6 through a nuclear factor-kappa B-dependent mechanism: suppression by gp120 specific small interfering RNA. PLoS One. 2011; 6(6):e21261. PMC: 3119684. DOI: 10.1371/journal.pone.0021261. View