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

被引：376

作者：

Morita, Masayuki ^{[1
]}

Kuba, Keiji ^{[1
]}

Ichikawa, Akihiko ^{[1
]}

Nakayama, Mizuho ^{[1
]}

Katahira, Jun ^{[2
]}

Iwamoto, Ryo ^{[4
,5
]}

Watanebe, Tokiko ^{[6
,7
,9
,11
]}

Sakabe, Saori ^{[6
,7
,11
]}

Daidoji, Tomo ^{[12
]}

Nakamura, Shota ^{[3
]}

Kadowaki, Ayumi ^{[1
]}

Ohto, Takayo ^{[1
]}

Nakanishi, Hiroki ^{[8
]}

Taguchi, Ryo ^{[8
]}

Nakaya, Takaaki ^{[12
]}

Murakami, Makoto ^{[13
]}

Yoneda, Yoshihiro ^{[2
]}

Arai, Hiroyuki ^{[4
]}

Kawaoka, Yoshihiro ^{[6
,7
,9
,11
]}

Penninger, Josef M. ^{[14
]}

Arita, Makoto ^{[4
,10
]}

Imai, Yumiko ^{[1
]}

机构：

[1] Akita Univ, Dept Biol Informat & Expt Therapeut, Grad Sch Med, Akita 0108543, Japan

[2] Osaka Univ, Biomol Networks Labs, Biomol Dynam Lab, Grad Sch Frontier Biosci, Osaka 5650871, Japan

[3] Osaka Univ, Dept Infect Metagen, Microbial Dis Res Inst, Osaka 5650871, Japan

[4] Univ Tokyo, Dept Hlth Chem, Tokyo 1130033, Japan

[5] Univ Tokyo, Business Acad Collaborat Lab, Grad Sch Pharmaceut Sci, Tokyo 1130033, Japan

[6] Univ Tokyo, Div Virol, Dept Microbiol & Immunol, Tokyo 1130033, Japan

[7] Univ Tokyo, Int Res Ctr Infect Dis, Inst Med Sci, Tokyo 1130033, Japan

[8] Univ Tokyo, Dept Metabolome, Grad Sch Med, Tokyo 1130033, Japan

[9] Japan Sci & Technol Agcy, ERATO Infect Induced Host Responses Project, Kawaguchi, Saitama 3320012, Japan

[10] Japan Sci & Technol Agcy, PRESTO, Kawaguchi, Saitama 3320012, Japan

[11] Univ Wisconsin, Influenza Res Inst, Madison, WI 53711 USA

[12] Kyoto Prefectural Univ Med, Dept Infect Dis, Kyoto 6028566, Japan

[13] Tokyo Metropolitan Inst Med Sci, Biomembrane Signaling Project, Tokyo 1568506, Japan

[14] Austrian Acad Sci, IMBA Inst Mol Biotechnol, A-1030 Vienna, Austria

来源：

CELL | 2013年 / 153卷 / 01期

基金：

日本科学技术振兴机构;

关键词：

MESSENGER-RNA EXPORT; NUCLEAR-PORE COMPLEX; INFLAMMATION; RESOLUTION; PATHWAYS; REVEALS; MICE; SEQ; EXPRESSION; DEPENDENCE;

D O I：

10.1016/j.cell.2013.02.027

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：112 / 125

页数：14

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