Transmission of HIV-1 CTL Escape Variants Provides HLA-Mismatched Recipients with a Survival Advantage

PLoS Pathogens

Salim Abdool Karim¹  Koleka Mlisana¹  Carolyn Williamson²  Florette Treurnicht²  Cathal Seoighe²  Darren P. Martin²  Denis R. Chopera²  Zenda Woodman²  Mandla Mlotshwa³  Debra Assis de Rosa³  Clive M. Gray³  Winston Hide⁴ 

[1] Centre for the AIDS Programme of Research in South Africa, University of Kwa-Zulu Natal, Durban, South Africa;Institute of Infectious Diseases and Molecular Medicine, Division of Medical Virology, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa;National Institute for Communicable Diseases, Johannesburg, South Africa;South African National Bioinformatics Institute, University of the Western Cape, Cape Town, South Africa

关键词: Microbial mutation;    Viral load;    Mutation;    Mutation detection;    HIV;    HIV-1;    Viral replication;    Enzyme-linked immunoassays;   

DOI  :  10.1371/journal.ppat.1000033

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY