The inducible amphisome isolates viral hemagglutinin and defends against influenza A virus infection

Jumpei Omi, Miho Watanabe-Takahashi, Katsura Igai, Eiko Shimizu, Ching Yi Tseng, Tomohiro Miyasaka, Tsuyoshi Waku, Shinichiro Hama, Rieka Nakanishi, Yuki Goto, Yuri Nishino, Atsuo Miyazawa, Yasuhiro Natori, Makoto Yamashita, Kiyotaka Nishikawa

研究成果: Article査読

4 被引用数 (Scopus)

抄録

The emergence of drug-resistant influenza type A viruses (IAVs) necessitates the development of novel anti-IAV agents. Here, we target the IAV hemagglutinin (HA) protein using multivalent peptide library screens and identify PVF-tet, a peptide-based HA inhibitor. PVF-tet inhibits IAV cytopathicity and propagation in cells by binding to newly synthesized HA, rather than to the HA of the parental virus, thus inducing the accumulation of HA within a unique structure, the inducible amphisome, whose production from the autophagosome is accelerated by PVF-tet. The amphisome is also produced in response to IAV infection in the absence of PVF-tet by cells overexpressing ABC transporter subfamily A3, which plays an essential role in the maturation of multivesicular endosomes into the lamellar body, a lipid-sorting organelle. Our results show that the inducible amphisomes can function as a type of organelle-based anti-viral machinery by sequestering HA. PVF-tet efficiently rescues mice from the lethality of IAV infection.

本文言語English
論文番号162
ジャーナルNature communications
11
1
DOI
出版ステータスPublished - 2020 12 1

ASJC Scopus subject areas

  • 化学 (全般)
  • 生化学、遺伝学、分子生物学(全般)
  • 物理学および天文学(全般)

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