TY - JOUR
T1 - Loss of HIV-1-derived cytotoxic T lymphocyte epitopes restricted by protective HLA-B alleles during the HIV-1 epidemic
AU - Schellens, Ingrid M. M.
AU - Navis, Marjon
AU - van Deutekom, Hanneke W. M.
AU - Boeser-Nunnink, Brigitte
AU - Berkhout, Ben
AU - Kootstra, Neeltje
AU - Miedema, Frank
AU - Keşmir, Can
AU - Schuitemaker, Hanneke
AU - van Baarle, Debbie
AU - Borghans, José A. M.
PY - 2011
Y1 - 2011
N2 - HIV-1 is known to adapt to the human immune system, leading to accumulation of escape mutations during the course of infection within an individual. Cross-sectional studies have shown an inverse correlation between the prevalence of human leukocyte antigen (HLA) alleles in a population and the number of cytotoxic T lymphocyte (CTL) escape mutations in epitopes restricted by those HLA alleles. Recently, it was demonstrated that at a population level HIV-1 is adapting to the humoral immune response, which is reflected in an increase in resistance to neutralizing antibodies over time. Here we investigated whether adaptations to cellular immunity have also accumulated during the epidemic. We compared the number of CTL epitopes in HIV-1 strains isolated from individuals who seroconverted at the beginning of the HIV-1 epidemic and from individuals who seroconverted in recent calendar time. The number of CTL epitopes in HIV-1 variants restricted by the most common HLA alleles in the population did not change significantly during the epidemic. In contrast, we found a significant loss of CTL epitopes restricted by HLA-B alleles associated with a low relative hazard of HIV-1 disease progression during the epidemic. Such a loss was not observed for CTL epitopes restricted by HLA-A alleles. Despite the large degree of HLA polymorphism, HIV-1 has accumulated adaptations to CTL responses within 20 years of the epidemic. The fact that such adaptations are driven by the HLA-B molecules that provide best protection against HIV-1 disease progression has important implications for our understanding of HIV evolution
AB - HIV-1 is known to adapt to the human immune system, leading to accumulation of escape mutations during the course of infection within an individual. Cross-sectional studies have shown an inverse correlation between the prevalence of human leukocyte antigen (HLA) alleles in a population and the number of cytotoxic T lymphocyte (CTL) escape mutations in epitopes restricted by those HLA alleles. Recently, it was demonstrated that at a population level HIV-1 is adapting to the humoral immune response, which is reflected in an increase in resistance to neutralizing antibodies over time. Here we investigated whether adaptations to cellular immunity have also accumulated during the epidemic. We compared the number of CTL epitopes in HIV-1 strains isolated from individuals who seroconverted at the beginning of the HIV-1 epidemic and from individuals who seroconverted in recent calendar time. The number of CTL epitopes in HIV-1 variants restricted by the most common HLA alleles in the population did not change significantly during the epidemic. In contrast, we found a significant loss of CTL epitopes restricted by HLA-B alleles associated with a low relative hazard of HIV-1 disease progression during the epidemic. Such a loss was not observed for CTL epitopes restricted by HLA-A alleles. Despite the large degree of HLA polymorphism, HIV-1 has accumulated adaptations to CTL responses within 20 years of the epidemic. The fact that such adaptations are driven by the HLA-B molecules that provide best protection against HIV-1 disease progression has important implications for our understanding of HIV evolution
U2 - https://doi.org/10.1097/QAD.0b013e32834981b3
DO - https://doi.org/10.1097/QAD.0b013e32834981b3
M3 - Article
C2 - 21681058
SN - 0269-9370
VL - 25
SP - 1691
EP - 1700
JO - AIDS (London, England)
JF - AIDS (London, England)
IS - 14
ER -