PMID- 17878955
OWN - NLM
STAT- MEDLINE
DCOM- 20100119
LR  - 20181113
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 2
IP  - 9
DP  - 2007 Sep 19
TI  - HLA alleles associated with slow progression to AIDS truly prefer to present 
      HIV-1 p24.
PG  - e920
LID - e920
AB  - BACKGROUND: The mechanism behind the association between human leukocyte antigen 
      (HLA) molecules and the rate of HIV-1 disease progression is still poorly 
      understood. Recent data suggest that "protective" HLA molecules, i.e. those 
      associated with a low HIV-1 viral load and relatively slow disease progression, 
      tend to present epitopes from the Gag capsid protein. Although this suggests that 
      preferential targeting of Gag delays disease progression, the apparent preference 
      for Gag could also be a side-effect of the relatively high immunogenicity of the 
      protein. METHODS AND FINDINGS: To separate cause and effect, we predicted HIV-1 
      epitopes from the whole genome of HIV-1, and found that protective HLA alleles 
      have a true preference for the p24 Gag protein, while non-protective HLA alleles 
      preferentially target HIV-1 Nef. In line with this, we found a significant 
      negative correlation between the predicted affinity of the best-binding p24 
      epitopes and the relative hazard of HIV-1 disease progression for a large number 
      of HLA molecules. When the epitopes targeted by protective HLA alleles were 
      mapped to the known p24 structure, we found that mutations in these epitopes are 
      likely to disturb the p24 dimer structure, which is expected to severely reduce 
      the fitness of the virus. CONCLUSIONS: Our results suggest that the intrinsic 
      preference of different HLA molecules to present p24 peptides explains why some 
      HLA molecules are more protective than others.
FAU - Borghans, Jose A M
AU  - Borghans JA
AD  - Theoretical Biology/Bioinformatics, Utrecht University, Utrecht, The Netherlands.
FAU - Molgaard, Anne
AU  - Molgaard A
FAU - de Boer, Rob J
AU  - de Boer RJ
FAU - Kesmir, Can
AU  - Kesmir C
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070919
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (HIV Core Protein p24)
RN  - 0 (HLA Antigens)
SB  - IM
MH  - *Alleles
MH  - Disease Progression
MH  - HIV Core Protein p24/chemistry/*metabolism
MH  - HIV Infections/*pathology
MH  - HIV-1
MH  - HLA Antigens/*genetics
MH  - Humans
MH  - Models, Molecular
PMC - PMC1976389
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2007/09/20 09:00
MHDA- 2007/09/20 09:01
PMCR- 2007/09/19
CRDT- 2007/09/20 09:00
PHST- 2007/07/09 00:00 [received]
PHST- 2007/08/16 00:00 [accepted]
PHST- 2007/09/20 09:00 [pubmed]
PHST- 2007/09/20 09:01 [medline]
PHST- 2007/09/20 09:00 [entrez]
PHST- 2007/09/19 00:00 [pmc-release]
AID - 07-PONE-RA-01697 [pii]
AID - 10.1371/journal.pone.0000920 [doi]
PST - epublish
SO  - PLoS One. 2007 Sep 19;2(9):e920. doi: 10.1371/journal.pone.0000920.