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HIV: An Ever-Moving Target

Associations between HIV polymorphisms and host HLA types could stymie CTL-based vaccine strategies.

Mutations in HIV genes that render host cytotoxic T lymphocytes (CTLs) unable to recognize the mutated virus are believed to be important in HIV pathogenesis. CTL activation requires antigen binding to HLA molecules, followed by interaction with the T-cell receptor. T-cell mediated immunity in each person is HLA-allele-specific. It now seems that specific HIV gene polymorphisms and host HLA types are linked.

Investigators determined the HLA genotypes of 473 HIV-positive patients in western Australia and ascertained the amino acid sequence between positions 20 and 227 of the HIV-1 reverse transcriptase (HIV-1 RT) of the patients' most recent HIV isolates. A multivariate analysis found 64 significant positive associations between specific HIV-1 RT polymorphisms and HLA alleles. Associations with a given HLA-linked polymorphism clustered at particular HIV-1 RT sequence locations. Fifteen polymorphisms were located at known CTL epitopes for their linked HLA alleles. Twenty-five additional polymorphisms were negatively associated with specific HLA alleles; most of these negative associations were with the most common of the HLA alleles in the subject population. The authors note that this finding is consistent with the possibility that HIV strains adapt to the most common HLA types in a population. HIV viral loads were higher in patients harboring HIV-1 RT polymorphisms specific for their HLA type. The association (positive or negative) between HLA alleles and HIV-1 RT polymorphisms better predicted viral load than either factor alone.

Comment: HIV's ability to adapt to its surroundings and evade host immune responses, CTLs in this case, through its high mutation frequency has major implications for understanding the disparities seen in the rates of HIV disease progression. It also raises concerns about the potential efficacy of CTL-based vaccine strategies.

— Bradley E. Britigan, MD

Published in Journal Watch Infectious Diseases July 12, 2002

Citation(s):

Moore CB et al. Evidence of HIV-1 adaptation to HLA-restricted immune responses at a population level. Science 2002 May 24; 296:1439-43.

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McMichael A and Klenerman P. HLA leaves its footprints on HIV. Science 2002 May 24; 296:1410-1.

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• Medline abstract (Free)