The Lipid Mediator Protectin D1 Inhibits Influenza Virus Replication and Improves Severe Influenza | Zendy

Masayuki Morita | Zendy; Keiji Kuba | Zendy; Akihiko Ichikawa | Zendy; Mizuho Nakayama | Zendy; Jun Katahira | Zendy; Ryo Iwamoto | Zendy; Tokiko Watanebe | Zendy; Saori Sakabe | Zendy; Tomo Daidoji | Zendy; Shota Nakamura | Zendy; Ayumi Kadowaki | Zendy; Takayo Ohto | Zendy; Hiroki Nakanishi | Zendy; Ryo Taguchi | Zendy; Takaaki Nakaya | Zendy; Makoto Murakami | Zendy; Yoshihiro Yoneda | Zendy; Hiroyuki Arai | Zendy; Yoshihiro Kawaoka | Zendy; Josef Penninger | Zendy; Makoto Arita | Zendy; Yumiko Imai | Zendy

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The Lipid Mediator Protectin D1 Inhibits Influenza Virus Replication and Improves Severe Influenza

Author(s) -

Masayuki Morita,

Keiji Kuba,

Akihiko Ichikawa,

Mizuho Nakayama,

Jun Katahira,

Ryo Iwamoto,

Tokiko Watanebe,

Saori Sakabe,

Tomo Daidoji,

Shota Nakamura,

Ayumi Kadowaki,

Takayo Ohto,

Hiroki Nakanishi,

Ryo Taguchi,

Takaaki Nakaya,

Makoto Murakami,

Yoshihiro Yoneda,

Hiroyuki Arai,

Yoshihiro Kawaoka,

Josef Penninger,

Makoto Arita,

Yumiko Imai

Publication year - 2013

Publication title -

cell

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 26.304

H-Index - 776

eISSN - 1097-4172

pISSN - 0092-8674

DOI - 10.1016/j.cell.2013.02.027

Subject(s) - biology , mediator , influenza a virus subtype h5n1 , virology , virus , viral replication , lipid signaling , influenza a virus , lipid metabolism , orthomyxoviridae , pandemic , h5n1 genetic structure , immunology , inflammation , disease , infectious disease (medical specialty) , covid-19 , microbiology and biotechnology , medicine , endocrinology

Influenza A viruses are a major cause of mortality. Given the potential for future lethal pandemics, effective drugs are needed for the treatment of severe influenza such as that caused by H5N1 viruses. Using mediator lipidomics and bioactive lipid screen, we report that the omega-3 polyunsaturated fatty acid (PUFA)-derived lipid mediator protectin D1 (PD1) markedly attenuated influenza virus replication via RNA export machinery. Production of PD1 was suppressed during severe influenza and PD1 levels inversely correlated with the pathogenicity of H5N1 viruses. Suppression of PD1 was genetically mapped to 12/15-lipoxygenase activity. Importantly, PD1 treatment improved the survival and pathology of severe influenza in mice, even under conditions where known antiviral drugs fail to protect from death. These results identify the endogenous lipid mediator PD1 as an innate suppressor of influenza virus replication that protects against lethal influenza virus infection.

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