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 and Kiyotaka Nishikawa ()
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Jumpei Omi: Graduate School of Life and Medical Sciences, Doshisha University
Miho Watanabe-Takahashi: Graduate School of Life and Medical Sciences, Doshisha University
Katsura Igai: Nagasaki University
Eiko Shimizu: Graduate School of Life and Medical Sciences, Doshisha University
Ching-Yi Tseng: Graduate School of Life and Medical Sciences, Doshisha University
Tomohiro Miyasaka: Doshisha University
Tsuyoshi Waku: Graduate School of Life and Medical Sciences, Doshisha University
Shinichiro Hama: Graduate School of Life and Medical Sciences, Doshisha University
Rieka Nakanishi: Graduate School of Life and Medical Sciences, Doshisha University
Yuki Goto: Graduate School of Life and Medical Sciences, Doshisha University
Yuri Nishino: University of Hyogo
Atsuo Miyazawa: University of Hyogo
Yasuhiro Natori: Iwate Medical University
Makoto Yamashita: University of Tokyo
Kiyotaka Nishikawa: Graduate School of Life and Medical Sciences, Doshisha University

Nature Communications, 2020, vol. 11, issue 1, 1-17

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41467-019-13974-w

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