Human immunodeficiency virus mutations during the first month of infection are preferentially found in known cytotoxic T-lymphocyte epitopes

Abstract

The full protein coding region of human immunodeficiency virus (HIV) genomes were sequenced using plasma collected from nine African-Americans prior to seroconversion and 7 to 28 days later. HIV mutations emerged in seven of these subjects at a genomewide rate of 2% per year. The location of nonsynonymous (NS) HIV mutations within these subjects was compared to their potential HLA-A and B types restricted CTL epitopes reported in the Los Alamos National Laboratory HIV immunology database. A statistically significant (P < 0.005) number of the early NS mutations (13.5%) were found within previously reported CTL epitopes. A virus sequencing and reported CTL epitopes database analysis therefore support a model where a significant proportion of very early nonsynonymous HIV mutations are selected by CTL.

FIG. 1.

Viral load, p24 antigenemia, and anti-HIV-1 serology of acute infections. Nine African-Americans were characterized as undergoing primary infection. Day 0: first plasma sample with detectable viral RNA using the UltraQual assay or the SuperQuant assay (threshold of 5 and 100 RNA copies/ml, respectively). -/+: negative and positive reactivity, respectively, for p24 and for anti-HIV-1 antibodies.

FIG. 2.

Genomewide distribution of early HIV mutations. The vertical bar represent one nucleotide substitution.