Influence of CD4+ T cell counts on viral evolution in HIV-infected individuals undergoing suppressive HAART.
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.
Lorenzo
Eric
E
AIDS Research Program, Ponce School of Medicine, Ponce 00732, Puerto Rico. elorenzo@psm.edu
Colon
Maria C
MC
Almodovar
Sharilyn
S
Maldonado
Irvin M
IM
Gonzalez
Sandra
S
Costa
Sonia E
SE
Hill
Martin D
MD
Mendoza
Rafael
R
Sepulveda
Gladys
G
Yanagihara
Richard
R
Nerurkar
Vivek
V
Kumar
Rakesh
R
Yamamura
Yasuhiro
Y
Scott
Walter A
WA
Kumar
Anil
A
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
D014759:Viral Envelope Proteins