Nucleotide and amino acid mutations in human immunodeficiency virus corresponding to CD4+ decline.
In a meta-analysis, gene sequences of the HIV-1 V3 and surrounding envelope region from studies examining longitudinally derived blood and plasma human immunodeficiency virus forms were analyzed for changes over disease course. CD4+ counts were used as a marker of disease progression; 58 subjects, followed an average of 56 months, were included. Genetic diversification was found early in disease progression. In mid-progression (CD4+ counts dropping from 488 to 329/mm3) diversification did not increase while loop charge dramatically increased. This is consistent with a charged form that dominates and induces disease progression at this critical time. Although the overall mean increase in loop charge was significant, this increase and the transition to amino acids known to change tropism occurred in only half of the subjects who progressed. Those with rapidly progressing disease (within 2 years post-infection) began with a loop charge similar to the end stage of normal progressors. DNA from blood-cell-derived sequences differed from concurrently obtained plasma counterparts by one nucleotide out of 238, but this difference was not reflected in differences in glycosylation patterns, loop charge, or tropism-conferring amino acids. Plasma-derived forms were poorer predictors of future viral forms than were cell-derived sequences.
Hill
M D
MD
Department of Pharmacology, Ponce School of Medicine, Ponce, Puerto Rico. mhill@psm.edu
Hernández
W
W
D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000821:virology*; D018450:Disease Progression; D014644:Genetic Variation; D015699:HIV Envelope Protein gp120 / Q000737:chemistry* / Q000235:genetics* / Q000276:immunology; D015658:HIV Infections / Q000276:immunology* / Q000821:virology*; D015497:HIV-1 / Q000235:genetics* / Q000276:immunology; D006801:Humans; D009154:Mutation; D010446:Peptide Fragments / Q000737:chemistry* / Q000235:genetics* / Q000276:immunology; D011533:Proviruses / Q000235:genetics; D012367:RNA, Viral / Q000097:blood / Q000235:genetics
D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D010446:Peptide Fragments; D012367:RNA, Viral