論文

査読有り 国際誌
2020年5月23日

N-terminal PreS1 Sequence Regulates Efficient Infection of Cell Culture-generated Hepatitis B Virus.

Hepatology (Baltimore, Md.)
  • Asako Murayama
  • ,
  • Norie Yamada
  • ,
  • Yoshiki Osaki
  • ,
  • Masaaki Shiina
  • ,
  • Hussein Hassan Aly
  • ,
  • Masashi Iwamoto
  • ,
  • Senko Tsukuda
  • ,
  • Koichi Watashi
  • ,
  • Mami Matsuda
  • ,
  • Ryosuke Suzuki
  • ,
  • Tomohisa Tanaka
  • ,
  • Kohji Moriishi
  • ,
  • Tetsuro Suzuki
  • ,
  • Hironori Nishitsuji
  • ,
  • Masaya Sugiyama
  • ,
  • Masashi Mizokami
  • ,
  • Kunitada Shimotohno
  • ,
  • Takaji Wakita
  • ,
  • Masamichi Muramatsu
  • ,
  • T Jake Liang
  • ,
  • Takanobu Kato

記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1002/hep.31308

BACKGROUND & AIMS: An efficient cell culture system for hepatitis B virus (HBV) is indispensable for research on viral characteristics and anti-viral reagents. Currently, for the HBV infection assay in cell culture, viruses derived from HBV genome-integrated cell lines of HepG2.2.15 or HepAD-38 are commonly used. However, these viruses are not suitable for the evaluation of polymorphism dependent-viral characteristics or resistant mutations against anti-viral reagents. HBV obtained by the transient transfection of the ordinary HBV molecular clone has limited infection efficiencies in cell culture. APPROACH & RESULTS: We found that an 11 amino acid deletion (d11) in the preS1 region enhances the infectivity of cell culture-generated HBV (HBVcc) to sodium taurocholate co-transporting polypeptide-transduced HepG2 (HepG2/NTCP) cells. Infection of HBVcc derived from a d11-introduced genotype C strain (GTC-d11) was approximately 10-fold more efficient than infection of wild-type GTC (GTC-wt), and the number of infected cells was comparable between GTC-d11- and HepG2.2.15-derived viruses when inoculated with the same genome equivalents. A time-dependent increase in pre-genomic RNA and efficient synthesis of covalently closed circular DNA were detected after infection with the GTC-d11 virus. The involvement of d11 in the L-HBs protein in the enhanced infectivity was confirmed by an HBV reporter virus and hepatitis D virus infection system. The binding step of the GTC-d11 virus onto the cell surface was responsible for this efficient infection. CONCLUSIONS: This system provides a powerful tool for studying the infection and propagation of HBV in cell culture, and also for developing the anti-viral strategy against HBV infection.

リンク情報
DOI
https://doi.org/10.1002/hep.31308
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/32446278

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