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研究発表を行った学会；
・International Union of Microbiological Societies 2011 Congress (Virus and host response)
September 11-16, 2011. [Sapporo, Japan]

タイトル；Effect of HLA class I-mediated selective pressure on HIV-1 accessory genes.

発表者；Zafrul Hasan　氏
　　　（熊本大学　エイズ学研究センター　上野プロ）
Abstract；
[Objectives] It is becoming evident that HLA class I (HLA-I)-restricted cytotoxic T lymphocyte responses represent a major selective force in driving evolution of structural and enzymatic components of HIV-1 (e.g., gag, pol, and env). However, what extent HLA-I alleles have impact on the polymorphic nature of accessory genes remain elusive despite their important role in viral replication in vivo.
[Design and Methods] The vif, vpr, and vpu (VVV) genes were amplified by PCR using plasma viruses isolated from treatment-naive, HLA-I-typed, chronically-infected individuals in Japan (n=240). To identify HLA-I-associated viral polymorphisms, we performed a phylogenetically-informed method incorporating the effects of HIV codon co-variation and linkage disequilibrium among HLA-I alleles.
[Results and Conclusion] We found 13 different HLA-HIV amino acid associations from 9 codons of VVV at false discovery rate 0.2 (q<0.2). They were 5, 5, and 3 different HLA-HIV associations at 3, 4, and 2 different codons in Vif, Vpr and Vpu, respectively, suggesting the VVV protein has less HLA targeted genetic part with compare to gag, pol and nef of HIV reported previously. In contrast, a plenty of intraprotein amino-acid codon co-variations (191 cases) were identified across the VVV proteins and, in particular, more than half of them (103 cases) were observed in the Vpu protein. This observation is consistent with the extensive sequence diversity of vpu at the population level, and also suggests that protein conformation and function may be preserved through many possible combinations of primary and secondary polymorphisms, immune-mediated or otherwise. Taken together, our study highlights that HLA-I alleles represent a subtle effect on genetic variability in VVV genes unlike the strong effects on the other parts of viral genomes.