Abstract
One of the most important genetic factors known to affect the rate of disease progression in HIV-infected individuals is the genotype at the Class I Human Leukocyte Antigen (HLA) locus, which determines the HIV peptides targeted by cytotoxic T-lymphocytes (CTLs). Individuals with HLA-B*57 or B*5801 alleles, for example, target functionally important parts of the Gag protein. Mutants that escape these CTL responses may have lower fitness than the wild-type and can be associated with slower disease progression. Transmission of the escape variant to individuals without these HLA alleles is associated with rapid reversion to wild-type. However, the question of whether infection with an escape mutant offers an advantage to newly infected hosts has not been addressed. Here we investigate the relationship between the genotypes of transmitted viruses and prognostic markers of disease progression and show that infection with HLA-B*57/B*5801 escape mutants is associated with lower viral load and higher CD4+ counts.
Highlights
Avoidance of host anti-viral responses is a major factor influencing the evolution of HIV genomes
Mutations associated with cytotoxic Tlymphocytes (CTLs) evasion can incur significant viral replicative fitness costs and some escape mutations have been associated with decreased viral loads
Slower HIV reproduction is thought to be one reason that Human Leukocyte Antigen (HLA)-B*57 and HLA-B*5801 positive people progress to AIDS more slowly than most other HIV infected persons
Summary
Avoidance of host anti-viral responses is a major factor influencing the evolution of HIV genomes. Evasion of CTL responses involves mutations within and around targeted epitopes that result in the peptide no longer binding to the Class I MHC grove, or non-recognition by the CTL T cell receptor, or interference with peptide processing [1,2,3,4,5]. These so-called CTL escape mutations have been associated with increased viral loads and more rapid disease progression [3,6,7,8].
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
