title: The lipid mediator protectin D1 inhibits influenza virus replication and improves severe influenza.
abstract: 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.
authors.affiliation: Department of Biological Informatics and Experimental Therapeutics, Graduate School of Medicine, Akita University, Akita 010-8543, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Morita
authors.forename: Keiji
authors.initials: K
authors.lastname: Kuba
authors.forename: Akihiko
authors.initials: A
authors.lastname: Ichikawa
authors.forename: Mizuho
authors.initials: M
authors.lastname: Nakayama
authors.forename: Jun
authors.initials: J
authors.lastname: Katahira
authors.forename: Ryo
authors.initials: R
authors.lastname: Iwamoto
authors.forename: Tokiko
authors.initials: T
authors.lastname: Watanebe
authors.forename: Saori
authors.initials: S
authors.lastname: Sakabe
authors.forename: Tomo
authors.initials: T
authors.lastname: Daidoji
authors.forename: Shota
authors.initials: S
authors.lastname: Nakamura
authors.forename: Ayumi
authors.initials: A
authors.lastname: Kadowaki
authors.forename: Takayo
authors.initials: T
authors.lastname: Ohto
authors.forename: Hiroki
authors.initials: H
authors.lastname: Nakanishi
authors.forename: Ryo
authors.initials: R
authors.lastname: Taguchi
authors.forename: Takaaki
authors.initials: T
authors.lastname: Nakaya
authors.forename: Makoto
authors.initials: M
authors.lastname: Murakami
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Yoneda
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Arai
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kawaoka
authors.forename: Josef M
authors.initials: JM
authors.lastname: Penninger
authors.forename: Makoto
authors.initials: M
authors.lastname: Arita
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Imai
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000818:Animals; D002460:Cell Line; D004281:Docosahexaenoic Acids / Q000032:analysis / Q000276:immunology* / Q000494:pharmacology; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000502:physiology*; D053124:Influenza A Virus, H5N1 Subtype / Q000502:physiology*; D051379:Mice; D009976:Orthomyxoviridae Infections / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D014779:Virus Replication / Q000187:drug effects
chemical_list: C487679:protectin D1; D004281:Docosahexaenoic Acids