Evidence for host-driven selection of the HIV type 1 vpr gene in vivo during HIV disease progression in a transfusion-acquired cohort.
An epidemiologically linked HIV-1-infected cohort, in which a nonprogressor donor infected two recipients who progressed to AIDS, was examined. Sequence analysis, over time, of HIV-1 vpr gene quasispecies from uncultured peripheral blood cells revealed an insertion of arginine at position 90 altering a highly conserved C-terminal motif, believed to play a role in Vpr nuclear targeting. Full genome analysis from each patient showed no gene defects in other gene regions, implying that the mutational selection was unique to the vpr gene. A detailed analysis of the vpr quasispecies showed very little amino acid diversity in the nonprogressing donor, whereas, following viral transmission, the amino acid diversity increased dramatically over time in tandem with disease progression in the two recipients. Although the R insertion at position 90 was present in all three individuals, the variable degree of additional amino acid changes over time may have influenced HIV disease in the nonprogressor donor and the two progressing recipients. These data provide the first evidence in favor of vpr gene evolution over time, which was host-driven. The status of the nonprogressing donor was consistent with a highly protective B-57 HLA type, which was absent in the two progressing recipients, implying a role for host HLA type and other immunologic selective pressures in vpr gene selection in vivo.
Cali
Leon
L
Nuclear Signalling Laboratory, Department of Biochemistry and Molecular Biology, Monash University, Monash, VIC 3800, Australia.
Wang
Bin
B
Mikhail
Meriet
M
Gill
Michael J
MJ
Beckthold
Brenda
B
Salemi
Marco
M
Jans
David A
DA
Piller
Sabine C
SC
Saksena
Nitin K
NK
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy / Q000635:transmission / Q000821:virology*; D000595:Amino Acid Sequence; D023241:Antiretroviral Therapy, Highly Active; D015331:Cohort Studies; D018450:Disease Progression; D016334:Genes, vpr; D015497:HIV-1 / Q000145:classification / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D010802:Phylogeny; D065227:Transfusion Reaction