Article Figures & Data
Figures
- FIG. 1.
The rate of mutation accumulation peaks early in HIV-1 infection. The mutation frequencies per amino acid residue per year in non-Env regions were calculated in two recent studies, with Bernardin et al. focusing on the first month after infection (Acute) (10) and Allen et al. focusing on 3 to 5 years after infection (Chronic) (2). The frequencies of NS mutations in non-Env regions in these two studies and our data (Early) are illustrated.
- FIG. 2.
Mutations preferentially arise within nonstructural and Env proteins. NS amino acid mutations were mapped onto individual proteins. After adjustment for length, the relative mutation frequencies at the amino acid level of each protein are shown, with nonstructural and Env proteins represented by solid bars.
- FIG. 3.
Distribution of forward and reverting mutations identified across the HIV-1 genome. Locations of identified amino acid mutations were determined in each of the seven longitudinally sampled subjects. NS amino acid mutations were categorized as forward mutations or reversions in reference to the clade B consensus sequence (2002) from the LANL HIV Sequence Database. The numbers of forward mutations and reversions of each patient are shown. For the four patients (PS3002, PS2008, PS2016, and PS2019) with samples from three time points, mutations were stratified according to either a fast mutation if they occurred within the first 6 months after infection or a slow mutation if they occurred during the second half of the year.
- FIG. 4.
Reversions dominate early HIV-1 evolution. The rates at which forward mutations (F) and reversions (R) arose were assessed in subjects PS3002, PS2008, PS2016, and PS2019. The numbers of forward mutations and reversions were stratified by time as shown, with reversions occurring significantly faster than forward mutations (P = 0.000004).
- FIG. 5.
Reversions occur rapidly at conserved residues. The entropy score of each residue was determined by using clade B sequences from the LANL HIV Sequence Database. Fast reversions, those occurring within 0 to 6 months, and slow reversions, those occurring between 7 and 12 months, were identified in subjects PS3002, PS2008, PS2016, and PS2019. Entropy scores of residues where fast and slow reversions arose were then plotted, with fast reversions predominately occurring at conserved residues (P = 0.0014).
- FIG. 6.
Mutations in Gag and Pol revert rapidly. The numbers of fast and slow reversions in each protein were determined, and ratios of fast reversions to slow reversions in different proteins are illustrated.
Tables
- TABLE 1.
HLA typing and sampling times of seven subjects
Patient HLA-A HLA-B HLA-C Sampling days PS2008 A01/02 B08/40 Cw03/07 0, 182, 377 PS3002 A01/31 B08/35 Cw04/07 0, 199, 385 PS2016 A02/24 B13/44 Cw05/06 0, 193, 380 PS2019 A24/24 B15/55 Cw03/03 0, 171, 367 PS1038 A03/11 B08/35 Cw04/07 0, 174 PS4048 A01/03 B37/38 Cw06/12 0, 143 PS1044 A03/11 B14/44 Cw08/16 0, 177
