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

HIV-1 CTL 逃逸变体的传播为 HLA 不匹配的接受者提供了生存优势

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作者:Denis R Chopera, Zenda Woodman, Koleka Mlisana, Mandla Mlotshwa, Darren P Martin, Cathal Seoighe, Florette Treurnicht, Debra Assis de Rosa, Winston Hide, Salim Abdool Karim, Clive M Gray, Carolyn Williamson; CAPRISA 002 Study Team

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.

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