HIV-1 strains from a cohort of American subjects reveal the presence of a V2 region extension unique to slow progressors and non-progressors.
OBJECTIVE
To determine the molecular nature of HIV-1 quasispecies and their evolution, in vivo over time, in an American cohort of 22 homosexual men [four rapid progressors (RP), 15 slow progressors (SP) and three long-term non-progressors (LTNP)], infected with HIV-1 between 1982 and 1983, and to assess the possible role of the HIV-1 V2 region extension in HIV disease progression.


METHODS
Genetic and phylogenetic analyses of the V3 region and the nef gene clones over time from uncultured peripheral blood mononuclear cells (PBMC) of American patients with varying HIV disease progression rates.


METHODS
Proviral DNA from longitudinally collected uncultured PBMC were subjected to PCR amplification in the nef gene and env V2 and V3 regions, followed by cloning, sequencing and phylogenetic analysis to establish evolutionary relationships between HIV-1 strains over time.


RESULTS
Analysis of multiple viral clones showed nef gene deletions/insertions in 10 out of 15 SP, along with the coexistence of intact and defective nef gene lineages in the same individual over time, whereas these nefgene abnormalities were absent from HIV-1 strains from LTNP. Increasing quasispecies diversity in HIV-1 strains, over time, abrogation of a V3 region N-linked glycosylation site in > 60% of the clones, and, importantly, an extended V2 region were unique features of HIV-1 strains from SP and LTNP.


CONCLUSIONS
The V2 region extension was unique to only SP and LTNP, and so may have a role in slow progression or non-progression of HIV disease. Increasing genetic diversity in HIV-1 strains in SP and LTNP correlated with the immunocompetent status of the host.
Wang
B
B
Retroviral Genetics Laboratory, Center for Virus Research, Westmead Hospital, University of Sydney, Australia.
Spira
T J
TJ
Owen
S
S
Lal
R B
RB
Saksena
N K
NK
D000595:Amino Acid Sequence; D001483:Base Sequence; D015331:Cohort Studies; D017931:DNA Primers; D018450:Disease Progression; D015754:Genes, nef; D015497:HIV-1 / Q000235:genetics / Q000302:isolation & purification* / Q000502:physiology; D018451:Homosexuality, Male; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid; D014779:Virus Replication / Q000502:physiology
D017931:DNA Primers