Abstract
Methods We included 27 individuals from the Amsterdam Cohort Studies on HIV infection and AIDS with a known seroconversion date in 1985 or 2005/06 (12 and 15 individuals, respectively), of which HIV sequences were derived within a year after seroconversion. CTL epitopes were predicted using a proteasomal cleavage/TAP transport/MHC class I combined predictor. HLA-binding epitopes from the proteins P17, P24, Nef, Protease and RT were predicted for 5 common HLA-A and 3 common HLA-B alleles, as well as for HLA-B27 and HLA-B57, the HLA-B alleles most strongly associated with slow progression to AIDS. To avoid the possibility that observed CTL escape mutations were due to within-host evolution rather than adaptation at the population level, individuals expressing the particular HLA allele under investigation were excluded from the analyses.
Highlights
HIV undergoes extensive within-host adaptation to HIVspecific Cytotoxic T Lymphocyte (CTL) responses
HLA-binding epitopes from the proteins P17, P24, Nef, Protease and RT were predicted for 5 common HLA-A and 3 common HLA-B alleles, as well as for HLA-B27 and HLA-B57, the HLA-B alleles most strongly associated with slow progression to AIDS
To avoid the possibility that observed CTL escape mutations were due to within-host evolution rather than adaptation at the population level, individuals expressing the particular HLA allele under investigation were excluded from the analyses
Summary
HIV undergoes extensive within-host adaptation to HIVspecific Cytotoxic T Lymphocyte (CTL) responses. Adaptation of HIV-1 to the human immune system at the population level is driven by protective HLA-B alleles Address: 1Immunology, University Medical Center Utrecht, Utrecht, Netherlands, 2Academic Medical Center, Amsterdam, Netherlands and 3Utrecht University, Utrecht, Netherlands
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