PMID- 20539088
OWN - NLM
STAT- MEDLINE
DCOM- 20110113
LR  - 20211020
IS  - 1473-5571 (Electronic)
IS  - 0269-9370 (Print)
IS  - 0269-9370 (Linking)
VI  - 24
IP  - 10
DP  - 2010 Jun 19
TI  - Correlates of spontaneous viral control among long-term survivors of perinatal 
      HIV-1 infection expressing human leukocyte antigen-B57.
PG  - 1425-35
LID - 10.1097/QAD.0b013e32833a2b5b [doi]
AB  - OBJECTIVE: We sought to identify immunologic and virologic correlates of 
      spontaneous viral control among long-term survivors of perinatal HIV infection 
      expressing the protective human leukocyte antigen (HLA)-B57 allele. DESIGN: The 
      frequency, epitope specificity, and functional attributes of HIV-specific T cells 
      and sequence variation within B57-restricted epitopes were compared between 
      'spontaneous controllers' who maintained normal CD4 percentages and viral loads 
      less than 3000 copies/ml without antiretroviral therapy, and 'treated 
      progressors' who had initiated HAART. METHODS: Recognition of HIV optimal 
      epitopes was assessed by interferon gamma (IFNgamma) enzyme-linked immunosorbent 
      spot. Functional characterization of CD8 cells targeting B57 epitopes was 
      performed by staining for cytokine production (intracellular IFNgamma, 
      interleukin-2, tumor necrosis factor alpha) and degranulation. Sequencing of 
      autologous RNA was performed to determine the prevalence of viral escape 
      mutations within B57-restricted epitopes and associated compensatory mutations. 
      RESULTS: HLA-B57 remained immunodominant during chronic infection in both 
      controllers and progressors, but controllers recognized fewer epitopes and 
      targeted epitopes within Gag and reverse transcriptase only, whereas progressors 
      demonstrated a broader response targeting additional proteins. No individual 
      epitope was targeted more frequently by spontaneous controllers. CD8 cytokine 
      production patterns were heterogeneous among individuals and even among different 
      epitopes in the same individual and did not correlate with spontaneous viral 
      control. Extensive sequence variation within B57 epitopes was observed in both 
      groups, but only progressors displayed additional capsid mutations that are known 
      to offset the viral fitness cost of B57-driven immune escape. CONCLUSION: Among 
      HLA-B57-positive long-term survivors, spontaneous control of viremia is not 
      associated with a qualitatively or quantitatively superior T-cell response, but 
      with uncompensated fitness-attenuating mutations in the viral capsid.
FAU - Tang, Yanhua
AU  - Tang Y
AD  - Ragon Institute of MGH, MIT, Charlestown, Massachusetts, USA.
FAU - Huang, Sihong
AU  - Huang S
FAU - Dunkley-Thompson, Jacqueline
AU  - Dunkley-Thompson J
FAU - Steel-Duncan, Julianne C
AU  - Steel-Duncan JC
FAU - Ryland, Elizabeth G
AU  - Ryland EG
FAU - St John, M Anne
AU  - St John MA
FAU - Hazra, Rohan
AU  - Hazra R
FAU - Christie, Celia D C
AU  - Christie CD
FAU - Feeney, Margaret E
AU  - Feeney ME
LA  - eng
GR  - R01 AI068497/AI/NIAID NIH HHS/United States
GR  - R01 AI068497-01A2/AI/NIAID NIH HHS/United States
GR  - R01-AI068497/AI/NIAID NIH HHS/United States
GR  - ImNIH/Intramural NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, N.I.H., Intramural
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)
RN  - 0 (HLA-B57 antigen)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Adolescent
MH  - CD4-Positive T-Lymphocytes/*immunology
MH  - CD8-Positive T-Lymphocytes/*immunology
MH  - Child
MH  - Epitopes, T-Lymphocyte/genetics/immunology
MH  - Female
MH  - HIV Infections/genetics/*immunology/virology
MH  - HIV Long-Term Survivors
MH  - *HIV-1/genetics/immunology
MH  - HLA-B Antigens/*immunology/metabolism
MH  - Humans
MH  - Immune Tolerance
MH  - Interferon-gamma/immunology/metabolism
MH  - Male
MH  - Viremia
PMC - PMC2903552
MID - NIHMS203679
EDAT- 2010/06/12 06:00
MHDA- 2011/01/14 06:00
PMCR- 2011/06/19
CRDT- 2010/06/12 06:00
PHST- 2010/06/12 06:00 [entrez]
PHST- 2010/06/12 06:00 [pubmed]
PHST- 2011/01/14 06:00 [medline]
PHST- 2011/06/19 00:00 [pmc-release]
AID - 00002030-201006190-00004 [pii]
AID - 10.1097/QAD.0b013e32833a2b5b [doi]
PST - ppublish
SO  - AIDS. 2010 Jun 19;24(10):1425-35. doi: 10.1097/QAD.0b013e32833a2b5b.