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PLoS Pathog ; 4(3): e1000033, 2008 Mar 21.
Article in English | MEDLINE | ID: mdl-18369479

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.


Subject(s)
Antigens, CD/immunology , HIV Infections/immunology , HIV-1/immunology , HLA-B Antigens/immunology , Mutation , Organic Cation Transport Proteins/immunology , gag Gene Products, Human Immunodeficiency Virus/immunology , Antigens, CD/genetics , CD4 Lymphocyte Count , Cohort Studies , Disease Progression , Epitopes, T-Lymphocyte/genetics , Epitopes, T-Lymphocyte/immunology , Female , Genetic Predisposition to Disease , Genotype , HIV Infections/transmission , HIV Infections/virology , HIV-1/genetics , HLA-B Antigens/genetics , Humans , Immunodominant Epitopes/genetics , Immunodominant Epitopes/immunology , Organic Cation Transport Proteins/genetics , Survival Rate , T-Lymphocytes, Cytotoxic/immunology , gag Gene Products, Human Immunodeficiency Virus/genetics
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