PMID- 21681058
OWN - NLM
STAT- MEDLINE
DCOM- 20111207
LR  - 20110831
IS  - 1473-5571 (Electronic)
IS  - 0269-9370 (Linking)
VI  - 25
IP  - 14
DP  - 2011 Sep 10
TI  - Loss of HIV-1-derived cytotoxic T lymphocyte epitopes restricted by protective 
      HLA-B alleles during the HIV-1 epidemic.
PG  - 1691-700
LID - 10.1097/QAD.0b013e32834981b3 [doi]
AB  - OBJECTIVE AND DESIGN: 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. 
      METHODS: 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. RESULTS: 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. CONCLUSION: 
      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.
FAU - Schellens, Ingrid M M
AU  - Schellens IM
AD  - aDepartment of Immunology, University Medical Center Utrecht, The Netherlands.
FAU - Navis, Marjon
AU  - Navis M
FAU - van Deutekom, Hanneke W M
AU  - van Deutekom HW
FAU - Boeser-Nunnink, Brigitte
AU  - Boeser-Nunnink B
FAU - Berkhout, Ben
AU  - Berkhout B
FAU - Kootstra, Neeltje
AU  - Kootstra N
FAU - Miedema, Frank
AU  - Miedema F
FAU - Kesmir, Can
AU  - Kesmir C
FAU - Schuitemaker, Hanneke
AU  - Schuitemaker H
FAU - van Baarle, Debbie
AU  - van Baarle D
FAU - Borghans, Jose A M
AU  - Borghans JA
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - AIDS
JT  - AIDS (London, England)
JID - 8710219
RN  - 0 (Epitopes, T-Lymphocyte)
RN  - 0 (HLA-B Antigens)
SB  - IM
MH  - Adult
MH  - Cross-Sectional Studies
MH  - Disease Progression
MH  - Epidemics
MH  - Epitopes, T-Lymphocyte/genetics/*immunology
MH  - Evolution, Molecular
MH  - Female
MH  - HIV Infections/*epidemiology/*immunology
MH  - HIV Seropositivity/genetics/*immunology
MH  - HIV-1/genetics/*immunology
MH  - HLA-B Antigens/genetics/*immunology
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Molecular Sequence Data
MH  - Phylogeny
MH  - T-Lymphocytes, Cytotoxic/*immunology
EDAT- 2011/06/18 06:00
MHDA- 2011/12/13 00:00
CRDT- 2011/06/18 06:00
PHST- 2011/06/18 06:00 [entrez]
PHST- 2011/06/18 06:00 [pubmed]
PHST- 2011/12/13 00:00 [medline]
AID - 10.1097/QAD.0b013e32834981b3 [doi]
PST - ppublish
SO  - AIDS. 2011 Sep 10;25(14):1691-700. doi: 10.1097/QAD.0b013e32834981b3.