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ID 116870
著者
Takemoto, Mai Tokushima University
Watanabe, Kyosuke Tokushima University
Yamamoto, Hideki Tokushima University
Nakashima, Satoshi Tokushima University
キーワード
HIV-1
Vif expression
SA1D2prox
nucleotide sequence
adaptation
splicing
資料タイプ
学術雑誌論文
抄録
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.
掲載誌名
Viruses
ISSN
19994915
出版者
MDPI
13
10
開始ページ
2079
発行日
2021-10-15
権利情報
This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
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出版社版DOI
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フルテキストファイル
言語
eng
著者版フラグ
出版社版
部局
医学系