論文

国際誌
2022年4月30日

Mutational spectrum of hepatitis C virus in patients with chronic hepatitis C determined by single molecule real-time sequencing.

Scientific reports
  • Fumiyasu Nakamura
  • Haruhiko Takeda
  • Yoshihide Ueda
  • Atsushi Takai
  • Ken Takahashi
  • Yuji Eso
  • Soichi Arasawa
  • Eriko Iguchi
  • Takahiro Shimizu
  • Masako Mishima
  • Ken Kumagai
  • Taiki Yamashita
  • Shinji Uemoto
  • Nobuyuki Kato
  • Hiroyuki Marusawa
  • Akihiro Sekine
  • Hiroshi Seno
  • 全て表示

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1
開始ページ
7083
終了ページ
7083
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1038/s41598-022-11151-6

The emergence of hepatitis C virus (HCV) with resistance-associated substitution (RAS), produced by mutations in the HCV genome, is a major problem in direct acting antivirals (DAA) treatment. This study aimed to clarify the mutational spectrum in HCV-RNA and the substitution pattern for the emergence of RASs in patients with chronic HCV infection. HCV-RNA from two HCV replicon cell lines and the serum HCV-RNA of four non-liver transplant and four post-liver transplant patients with unsuccessful DAA treatment were analyzed using high-accuracy single-molecule real-time long-read sequencing. Transition substitutions, especially A>G and U>C, occurred prominently under DAAs in both non-transplant and post-transplant patients, with a mutational bias identical to that occurring in HCV replicon cell lines during 10-year culturing. These mutational biases were reproduced in natural courses after DAA treatment. RASs emerged via both transition and transversion substitutions. NS3-D168 and NS5A-L31 RASs resulted from transversion mutations, while NS5A-Y93 RASs was caused by transition substitutions. The fidelity of the RNA-dependent RNA polymerase, HCV-NS5B, produces mutational bias in the HCV genome, characterized by dominant transition mutations, notably A>G and U>C substitutions. However, RASs are acquired by both transition and transversion substitutions, and the RASs-positive HCV clones are selected and proliferated under DAA treatment pressure.

リンク情報
DOI
https://doi.org/10.1038/s41598-022-11151-6
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/35490163
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9056513
ID情報
  • DOI : 10.1038/s41598-022-11151-6
  • PubMed ID : 35490163
  • PubMed Central 記事ID : PMC9056513

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