Identification and molecular characterization of SIV Vpr R50G mutation associated with long term survival in SIV-infected morphine dependent and control macaques

•We examined SIV vpr evolution from control and morphine-dependent macaques.•We detected a change (R50G) in Vpr that was present in macaques that survived.•The R50G change in Vpr results in altered protein structure, localization and function.

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.