title: Influence of CD4+ T cell counts on viral evolution in HIV-infected individuals undergoing suppressive HAART.
abstract: We analyzed the viral C2-V4 envelope diversity, glycosylation patterns, and dS/dN ratios of plasma HIV-1 in an attempt to better understand the complex interaction between viral quasispecies and the host-selective pressures pre- and post-HAART. Phylogenetic analysis of the envelope gene of five patients revealed monophyletic clustering in patients with higher CD4+ T cell counts and sequence intermingling in those with lower CD4+ T cells in relation to the stage of HAART. Our analyses also showed clear shifts in N-linked glycosylation patterns in patients with higher CD4+ T cells, suggesting possible distinct immunological pressures pre- and post-HAART. The relative preponderance of synonymous/nonsynonymous changes in the envelope region suggested a positive selection in patients with higher CD4+ T cells, whereas lack of evidence for positive selection was found in the patients with lower CD4+ T cells. An exception to the last analysis occurred in the only patient who reached complete viral suppression, maybe due to drug pressure exerted over the pol gene that may obscure the immune pressure/selection at the envelope in this analysis. All these indications may suggest that even when HAART generates viral suppression, quasispecies evolve in the envelope gene probably resulting from host-selective pressure.
authors.affiliation: AIDS Research Program, Ponce School of Medicine, Ponce 00732, Puerto Rico. elorenzo@psm.edu
authors.forename: Eric
authors.initials: E
authors.lastname: Lorenzo
authors.forename: Maria C
authors.initials: MC
authors.lastname: Colon
authors.forename: Sharilyn
authors.initials: S
authors.lastname: Almodovar
authors.forename: Irvin M
authors.initials: IM
authors.lastname: Maldonado
authors.forename: Sandra
authors.initials: S
authors.lastname: Gonzalez
authors.forename: Sonia E
authors.initials: SE
authors.lastname: Costa
authors.forename: Martin D
authors.initials: MD
authors.lastname: Hill
authors.forename: Rafael
authors.initials: R
authors.lastname: Mendoza
authors.forename: Gladys
authors.initials: G
authors.lastname: Sepulveda
authors.forename: Richard
authors.initials: R
authors.lastname: Yanagihara
authors.forename: Vivek
authors.initials: V
authors.lastname: Nerurkar
authors.forename: Rakesh
authors.initials: R
authors.lastname: Kumar
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Yamamura
authors.forename: Walter A
authors.initials: WA
authors.lastname: Scott
authors.forename: Anil
authors.initials: A
authors.lastname: Kumar
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000097:blood / Q000188:drug therapy* / Q000276:immunology*; D000595:Amino Acid Sequence; D023241:Antiretroviral Therapy, Highly Active; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D015497:HIV-1 / Q000145:classification / Q000276:immunology* / Q000302:isolation & purification; D006801:Humans; D008969:Molecular Sequence Data; D010802:Phylogeny; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014759:Viral Envelope Proteins / Q000097:blood / Q000737:chemistry* / Q000235:genetics
chemical_list: D014759:Viral Envelope Proteins