@article{eedbb17ce3424c909934e98f9c6d608b,
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.",
author = "Masayuki Morita and Keiji Kuba and Akihiko Ichikawa and Mizuho Nakayama and Jun Katahira and Ryo Iwamoto and Tokiko Watanebe and Saori Sakabe and Tomo Daidoji and Shota Nakamura and Ayumi Kadowaki and Takayo Ohto and Hiroki Nakanishi and Ryo Taguchi and Takaaki Nakaya and Makoto Murakami and Yoshihiro Yoneda and Hiroyuki Arai and Yoshihiro Kawaoka and Penninger, {Josef M.} and Makoto Arita and Yumiko Imai",
note = "Funding Information: We thank all members of our laboratories for helpful discussions. We gratefully thank Ms. Michiko Kamio for technical assistance on LC-MS/MS analyses. Y.I. and K.K. are supported by the Funding Program for Next Generation World-Leading Researchers (NEXT Program, JSPS). Y.K. is supported by the “Center of Education and Research for the Advanced Genome-Based Medicine-For Personalized Medicine and the Control of Worldwide Infectious Diseases,” by a grant-in-aid for Specially Promoted Research and by the Japan Initiative for Global Research Network on Infectious Diseases from the Ministry of Education, Culture, Sports, Science and Technology, by ERATO (Japan Science and Technology Agency), and by Public Health Service research grants from the National Institute of Allergy and Infectious Diseases. M.A. is supported by a grant-in-aid from the Japan Science and Technology Agency Precursory Research for Embryonic Science and Technology (PRESTO), and a grant-in-aid from the Ministry of Education, Culture, Sports, Science, and Technology of Japan. J.M.P. is supported by IMBA and an Advanced ERC grant by the European Union. H.A. and M.A. are supported in part by the Program for Promotion of Basic and Applied Research for Innovations in Bio-Oriented Industry. ",
year = "2013",
month = mar,
day = "28",
doi = "10.1016/j.cell.2013.02.027",
language = "English",
volume = "153",
pages = "112--125",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "1",
}