Functional conservation of HIV-1 Vpr and variability in a mother-child pair of long-term non-progressors.
Increasing evidence suggests that HIV-1 Vpr is required in vivo for viral pathogenesis. Since Vpr displays multiple activities, little is known about which Vpr-specific activities are conserved in naturally occurring viruses or how natural mutations in Vpr might modulate viral pathogenesis in HIV-infected individuals. The goals of this study were to evaluate the functional variability of Vpr in naturally occurring viruses. The Vpr-specific activities of nuclear localization, induction of cell cycle G2 arrest and cell death were compared between viruses isolated from the fast progressing AIDS patients and a mother-child pair of long-term non-progressors (LTNPs). Wild-type Vpr activities were found in all of the viruses that were isolated from the fast progressing AIDS patients except for the truncated Vpr(IIIB) which lacked these activities. In contrast, defective Vpr were readily detected in viral populations isolated, over an 11-year period, from the mother-child pair. Sequence analyses indicated that these Vpr carried unique amino acid substitutions that frequently interrupted a highly conserved domain containing an N-terminal alpha-helix-turn-alpha-helix. Thus, Vpr activities are generally conserved in naturally occurring viruses. The functionally defective Vpr identified in the mother-child pair of LTNPs are likely to be unique and may possibly contribute to the slow disease progression.
D000293:Adolescent; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D016923:Cell Death / Q000187:drug effects; D002467:Cell Nucleus / Q000378:metabolism; D005260:Female; D016195:G2 Phase / Q000187:drug effects; D016336:Gene Products, vpr / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D014644:Genetic Variation; D015658:HIV Infections / Q000821:virology*; D020276:HIV Long-Term Survivors; D015497:HIV-1 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D018445:Infectious Disease Transmission, Vertical; D008969:Molecular Sequence Data; D012568:Schizosaccharomyces; D017422:Sequence Analysis, DNA; D054325:vpr Gene Products, Human Immunodeficiency Virus
D016336:Gene Products, vpr; D054325:vpr Gene Products, Human Immunodeficiency Virus