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

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

doi:10.1371/journal.ppat.1000033

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

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

Authors

Denis R Chopera¹, 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

Affiliation

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

Antigens, CD
Epitopes, T-Lymphocyte
HLA-B Antigens
HLA-B57 antigen
Immunodominant Epitopes
Organic Cation Transport Proteins
SLC44A1 protein, human
gag Gene Products, Human Immunodeficiency Virus

Abstract

Publication types

MeSH terms

Substances

Grants and funding