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PLoS Pathog. 2008 Mar 21;4(3):e1000033. doi: 10.1371/journal.ppat.1000033.

Transmission of HIV-1 CTL escape variants provides HLA-mismatched recipients with a survival advantage.

Author information

1
Institute of Infectious Diseases and Molecular Medicine, Division of Medical Virology, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.

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.

PMID:
18369479
PMCID:
PMC2265427
DOI:
10.1371/journal.ppat.1000033
[Indexed for MEDLINE]
Free PMC Article

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