SIV Vpr evolution is inversely related to disease progression in a morphine-dependent rhesus macaque model of AIDS.
Three of six morphine-dependent monkeys progressed rapidly to AIDS and died by 20 weeks in our SIV/SHIV non-human primate model of drug addiction and AIDS. We studied the evolution of the SIV vpr gene in both cerebrospinal fluid (CSF) and plasma in these rapid progressors, in their normal progressor counterparts and in infected, drug-free controls at 12 and 20 weeks post infection. Viral RNA was amplified, cloned, and sequenced to permit phylogenetic analyses of diversity and divergence of the vpr locus. As we found for SIV tat and env, the vpr gene evolves inversely to the rate of disease progression. Further, we found evidence that compartmentalization of the virus in plasma and CSF is significantly greater in the normal progressors than in the morphine-dependent, rapid progressors. Interestingly, although our previous work with the accessory gene nef indicated no association between disease progression and evolution, the accessory factor, vpr, behaves similarly to the essential lentiviral genes tat and env.
Noel
Richard J
RJ
Department of Biochemistry, Ponce School of Medicine, Ponce, PR 00716, USA. rnoel@psm.edu
Kumar
Anil
A
D000163:Acquired Immunodeficiency Syndrome / Q000378:metabolism / Q000821:virology; D000595:Amino Acid Sequence; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D004195:Disease Models, Animal; D018450:Disease Progression; D019143:Evolution, Molecular; D016336:Gene Products, vpr / Q000097:blood / Q000134:cerebrospinal fluid / Q000235:genetics / Q000378:metabolism*; D014644:Genetic Variation; D008253:Macaca mulatta / Q000821:virology; D008297:Male; D008969:Molecular Sequence Data; D009021:Morphine Dependence; D010802:Phylogeny; D016097:Simian Acquired Immunodeficiency Syndrome / Q000473:pathology* / Q000821:virology*; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000502:physiology*; D054325:vpr Gene Products, Human Immunodeficiency Virus
D000596:Amino Acids; D016336:Gene Products, vpr; D054325:vpr Gene Products, Human Immunodeficiency Virus