Transmission of HIV-1 CTL escape variants provides HLA-mismatched recipients with a survival advantage.
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.
Chopera
Denis R
DR
Institute of Infectious Diseases and Molecular Medicine, Division of Medical Virology, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
Woodman
Zenda
Z
Mlisana
Koleka
K
Mlotshwa
Mandla
M
Martin
Darren P
DP
Seoighe
Cathal
C
Treurnicht
Florette
F
de Rosa
Debra Assis
DA
Hide
Winston
W
Karim
Salim Abdool
SA
Gray
Clive M
CM
Williamson
Carolyn
C
D015703:Antigens, CD / Q000235:genetics / Q000276:immunology*; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D018450:Disease Progression; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D015658:HIV Infections / Q000276:immunology* / Q000635:transmission / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D015235:HLA-B Antigens / Q000235:genetics / Q000276:immunology*; D006801:Humans; D016056:Immunodominant Epitopes / Q000235:genetics / Q000276:immunology; D009154:Mutation; D027701:Organic Cation Transport Proteins / Q000235:genetics / Q000276:immunology*; D015996:Survival Rate; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000276:immunology*
D015703:Antigens, CD; D018984:Epitopes, T-Lymphocyte; D015235:HLA-B Antigens; C103707:HLA-B57 antigen; D016056:Immunodominant Epitopes; D027701:Organic Cation Transport Proteins; C510732:SLC44A1 protein, human; D054301:gag Gene Products, Human Immunodeficiency Virus