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

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number162
JournalNature communications
Volume11
Issue number1
DOIs
Publication statusPublished - 2020 Dec 1

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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