PMID- 20567513
OWN - NLM
STAT- MEDLINE
DCOM- 20100901
LR  - 20211020
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 5
IP  - 6
DP  - 2010 Jun 17
TI  - HLA-associated immune pressure on Gag protein in CRF01_AE-infected individuals 
      and its association with plasma viral load.
PG  - e11179
LID - 10.1371/journal.pone.0011179 [doi]
LID - e11179
AB  - BACKGROUND: The human leukocyte antigen (HLA)-restricted cytotoxic T-lymphocyte 
      (CTL) immune response is one of the major factors determining the genetic 
      diversity of human immunodeficiency virus (HIV). There are few population-based 
      analyses of the amino acid variations associated with the host HLA type and their 
      clinical relevance for the Asian population. Here, we identified HLA-associated 
      polymorphisms in the HIV-1 CRF01_AE Gag protein in infected married couples, and 
      examined the consequences of these HLA-selected mutations after transmission to 
      HLA-unmatched recipients. METHODOLOGY/PRINCIPAL FINDINGS: One hundred sixteen 
      HIV-1-infected couples were recruited at a government hospital in northern 
      Thailand. The 1.7-kb gag gene was amplified and directly sequenced. We identified 
      56 associations between amino acid variations in Gag and HLA alleles. Of those 
      amino acid variations, 35 (62.5%) were located within or adjacent to regions 
      reported to be HIV-specific CTL epitopes restricted by the relevant HLA. 
      Interestingly, a significant number of HLA-associated amino acid variations 
      appear to be unique to the CRF01_AE-infected Thai population. Variations in the 
      capsid protein (p24) had the strongest associations with the viral load and CD4 
      cell count. The mutation and reversion rates after transmission to a host with a 
      different HLA environment varied considerably. The p24 T242N variant escape from 
      B57/58 CTL had a significant impact on the HIV-1 viral load of CRF01_AE-infected 
      patients. CONCLUSIONS/SIGNIFICANCE: HLA-associated amino acid mutations and the 
      CTL selection pressures on the p24 antigen appear to have the most significant 
      impact on HIV replication in a CRF01_AE-infected Asian population. HLA-associated 
      mutations with a low reversion rate accumulated as a footprint in this Thai 
      population. The novel HLA-associated mutations identified in this study encourage 
      us to acquire more extensive information about the viral dynamics of 
      HLA-associated amino acid polymorphisms in a given population as effective CTL 
      vaccine targets.
FAU - Gesprasert, Goragoch
AU  - Gesprasert G
AD  - Department of Microbiology, Faculty of Science, Mahidol University, Bangkok, 
      Thailand.
FAU - Wichukchinda, Nuanjun
AU  - Wichukchinda N
FAU - Mori, Masahiko
AU  - Mori M
FAU - Shiino, Teiichiro
AU  - Shiino T
FAU - Auwanit, Wattana
AU  - Auwanit W
FAU - Sriwanthana, Busarawan
AU  - Sriwanthana B
FAU - Pathipvanich, Panita
AU  - Pathipvanich P
FAU - Sawanpanyalert, Pathom
AU  - Sawanpanyalert P
FAU - Miura, Toshiyuki
AU  - Miura T
FAU - Auewarakul, Prasert
AU  - Auewarakul P
FAU - Thitithanyanont, Arunee
AU  - Thitithanyanont A
FAU - Ariyoshi, Koya
AU  - Ariyoshi K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100617
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (DNA Primers)
RN  - 0 (Gene Products, gag)
RN  - 0 (HLA Antigens)
SB  - IM
MH  - Alleles
MH  - Base Sequence
MH  - DNA Primers
MH  - Gene Products, gag/*genetics
MH  - HIV Infections/*immunology/transmission/virology
MH  - HLA Antigens/genetics/*immunology
MH  - Mutation
MH  - Polymerase Chain Reaction
MH  - T-Lymphocytes, Cytotoxic/immunology
MH  - *Viral Load
PMC - PMC2887364
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2010/06/23 06:00
MHDA- 2010/09/02 06:00
PMCR- 2010/06/17
CRDT- 2010/06/23 06:00
PHST- 2010/01/05 00:00 [received]
PHST- 2010/05/15 00:00 [accepted]
PHST- 2010/06/23 06:00 [entrez]
PHST- 2010/06/23 06:00 [pubmed]
PHST- 2010/09/02 06:00 [medline]
PHST- 2010/06/17 00:00 [pmc-release]
AID - 10-PONE-RA-15317R1 [pii]
AID - 10.1371/journal.pone.0011179 [doi]
PST - epublish
SO  - PLoS One. 2010 Jun 17;5(6):e11179. doi: 10.1371/journal.pone.0011179.