駒, 貴明 Tokushima University 徳島大学 教育研究者総覧 KAKEN研究者をさがす
土肥, 直哉 Tokushima University 徳島大学 教育研究者総覧
Takemoto, Mai Tokushima University
Watanabe, Kyosuke Tokushima University
Yamamoto, Hideki Tokushima University
Nakashima, Satoshi Tokushima University
足立, 昭夫 Kansai Medical University 徳島大学 教育研究者総覧 KAKEN研究者をさがす
野間口, 雅子 Tokushima University 徳島大学 教育研究者総覧 KAKEN研究者をさがす
HIV-1 Vif plays an essential role in viral replication by antagonizing anti-viral cellular restriction factors, a family of APOBEC3 proteins. We have previously shown that naturally-occurring single-nucleotide mutations in the SA1D2prox region, which surrounds the splicing acceptor 1 and splicing donor 2 sites of the HIV-1 genome, dramatically alter the Vif expression level, resulting in variants with low or excessive Vif expression. In this study, we investigated how these HIV-1 variants with poor replication ability adapt and evolve under the pressure of APOBEC3 proteins. Adapted clones obtained through adaptation experiments exhibited an altered replication ability and Vif expression level compared to each parental clone. While various mutations were present throughout the viral genome, all replication-competent adapted clones with altered Vif expression levels were found to bear them within SA1D2prox, without exception. Indeed, the mutations identified within SA1D2prox were responsible for changes in the Vif expression levels and altered the splicing pattern. Moreover, for samples collected from HIV-1-infected patients, we showed that the nucleotide sequences of SA1D2prox can be chronologically changed and concomitantly affect the Vif expression levels. Taken together, these results demonstrated the importance of the SA1D2prox nucleotide sequence for modulating the Vif expression level during HIV-1 replication and adaptation.
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