HIV-1 strains from a cohort of American subjects reveal the presence of a V2 region extension unique to slow progressors and non-progressors

Objectives: To determine the molecular nature of HIV-I quasispecies and the ir 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 (LTN)], infected with HIV-1 between 1982 and 1983, and to assess the possible role of the HIV-1 V2 region extension in HIV disease pr ogression. Design: 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 su bjected to PCR amplification in the nef gene and env V2 and V3 regions, fol lowed by cloning, sequencing and phylogenetic analysis to establish evoluti onary relationships between HIV-1 strains over time. Results: Analysis of multiple viral clones showed nef gene deletions/insert ions 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 nef gene abnormalities were absent from HIV-1 strains from LTNP. Increasing quasisp ecies diversity in HIV-1 strains, over lime, abrogation of a V3 region N-li nked glycosylation site in > 60% of the clones, and, importantly, an extend ed V2 region were unique features or HIV-I 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. Inc reasing genetic diversity in HIV-1 strains in SP and LTNP correlated with t he immunocompetent status of the host. (C) 2000 Lippincott Williams & Wilki ns.