Publication: HLA-Associated immune pressure on gag protein in CRF01_AE-Infected individuals and its association with plasma viral load
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Issued Date
2010-08-11
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ISSN
19326203
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2-s2.0-77956202588
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Mahidol University
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SCOPUS
Bibliographic Citation
PLoS ONE. Vol.5, No.6 (2010)
Suggested Citation
Goragoch Gesprasert, Nuanjun Wichukchinda, Masahiko Mori, Teiichiro Shiino, Wattana Auwanit, Busarawan Sriwanthana, Panita Pathipvanich, Pathom Sawanpanyalert, Toshiyuki Miura, Prasert Auewarakul, Arunee Thitithanyanont, Koya Ariyoshi HLA-Associated immune pressure on gag protein in CRF01_AE-Infected individuals and its association with plasma viral load. PLoS ONE. Vol.5, No.6 (2010). doi:10.1371/journal.pone.0011179 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/28474
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Title
HLA-Associated immune pressure on gag protein in CRF01_AE-Infected individuals and its association with plasma viral load
Abstract
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 HLAassociated 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. © 2010 Gesprasert et al.