The lipid mediator protectin D1 inhibits influenza virus replication and improves severe influenza
- PMID: 23477864
- DOI: 10.1016/j.cell.2013.02.027
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.
Copyright © 2013 Elsevier Inc. All rights reserved.
Comment in
-
Antimicrobials: fat chance for influenza.Nat Rev Microbiol. 2013 May;11(5):298. doi: 10.1038/nrmicro3012. Epub 2013 Mar 25. Nat Rev Microbiol. 2013. PMID: 23524519 No abstract available.
-
Infectious diseases: Novel agents fight flu infection.Nat Rev Drug Discov. 2013 May;12(5):345. doi: 10.1038/nrd4013. Epub 2013 Apr 19. Nat Rev Drug Discov. 2013. PMID: 23598508 No abstract available.
-
The greasy response to virus infections.Cell Host Microbe. 2013 Apr 17;13(4):375-7. doi: 10.1016/j.chom.2013.04.002. Cell Host Microbe. 2013. PMID: 23601099 Free PMC article.
-
Lessons from lipids in the fight against influenza.Cell. 2013 Jul 3;154(1):22-3. doi: 10.1016/j.cell.2013.06.024. Cell. 2013. PMID: 23827671
Similar articles
-
Lessons from lipids in the fight against influenza.Cell. 2013 Jul 3;154(1):22-3. doi: 10.1016/j.cell.2013.06.024. Cell. 2013. PMID: 23827671
-
Low-dose interferon Type I treatment is effective against H5N1 and swine-origin H1N1 influenza A viruses in vitro and in vivo.J Interferon Cytokine Res. 2011 Jun;31(6):515-25. doi: 10.1089/jir.2010.0071. Epub 2011 Feb 16. J Interferon Cytokine Res. 2011. PMID: 21323570
-
Antiviral activity of the proteasome inhibitor VL-01 against influenza A viruses.Antiviral Res. 2011 Sep;91(3):304-13. doi: 10.1016/j.antiviral.2011.07.006. Epub 2011 Jul 13. Antiviral Res. 2011. PMID: 21777621
-
Role of omega-3 PUFA-derived mediators, the protectins, in influenza virus infection.Biochim Biophys Acta. 2015 Apr;1851(4):496-502. doi: 10.1016/j.bbalip.2015.01.006. Epub 2015 Jan 22. Biochim Biophys Acta. 2015. PMID: 25617737 Review.
-
Importance of interferon inducible trans-membrane proteins and retinoic acid inducible gene I for influenza virus replication: A review.Crit Rev Microbiol. 2016;42(1):75-82. doi: 10.3109/1040841X.2014.886553. Epub 2015 Mar 26. Crit Rev Microbiol. 2016. PMID: 25811941 Review.
Cited by
-
The inflammatory response triggered by Influenza virus: a two edged sword.Inflamm Res. 2017 Apr;66(4):283-302. doi: 10.1007/s00011-016-0996-0. Epub 2016 Oct 15. Inflamm Res. 2017. PMID: 27744631 Review.
-
Protectins: Their biosynthesis, metabolism and structure-functions.Biochem Pharmacol. 2022 Dec;206:115330. doi: 10.1016/j.bcp.2022.115330. Epub 2022 Oct 28. Biochem Pharmacol. 2022. PMID: 36341938 Free PMC article. Review.
-
Human Influenza Virus Infections.Semin Respir Crit Care Med. 2016 Aug;37(4):487-500. doi: 10.1055/s-0036-1584801. Epub 2016 Aug 3. Semin Respir Crit Care Med. 2016. PMID: 27486731 Free PMC article. Review.
-
Gut Microbiota Dysbiosis-Immune Hyperresponse-Inflammation Triad in Coronavirus Disease 2019 (COVID-19): Impact of Pharmacological and Nutraceutical Approaches.Microorganisms. 2020 Oct 1;8(10):1514. doi: 10.3390/microorganisms8101514. Microorganisms. 2020. PMID: 33019592 Free PMC article. Review.
-
Alterations in Epidermal Eicosanoid Metabolism Contribute to Inflammation and Impaired Late Differentiation in FLG-Mutated Atopic Dermatitis.J Invest Dermatol. 2017 Mar;137(3):706-715. doi: 10.1016/j.jid.2016.09.034. Epub 2016 Oct 26. J Invest Dermatol. 2017. PMID: 27793761 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Molecular Biology Databases
