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Influenza viral manipulation of S1P-metabolizing enzymes: Novel t | 3365
Virology & Mycology

Virology & Mycology
Open Access

ISSN: 2161-0517

+44 1223 790975

Influenza viral manipulation of S1P-metabolizing enzymes: Novel targets for anti-influenza therapy?


International Conference on Flu

June 08-10, 2015 Chicago, USA

Bumsuk Hahm , Chuan Xia, Madhuvanthi Vijayan, Young-Jin Seo, Curtis Pritzl and Stephen Alexander

Posters-Accepted Abstracts: Virol-mycol

Abstract :

Sphingosine 1-phosphate (S1P)-metabolizing enzymes regulate the level of bioactive sphingolipids and mediate important biological processes. S1P lyase induces the degradation of S1P while sphingosine kinase (SphK) generates S1P from sphingosine. In this study, we investigated the role of S1P lyase and SphK in host defense to influenza virus infection. Importantly, influenza virus infection increased the expression and activation of SphK, whereas the infection reduced the level of S1P lyase. To further study the detailed function of S1P lyase and SphK during influenza virus replication, biochemical, genetic, and pharmacological systems were employed. The results indicate that S1P lyase displayed anti-viral activity by rendering cells resistant to influenza virus infection and viral cytopathogenicity. S1P lyase directly promoted type I IFN signaling pathway, leading to the elevated STAT1/STAT2 activation and heightened expression of interferon-stimulated genes. In contrast to S1P lyase, overexpression of SphK enhanced the production of infectious influenza viruses and the inhibition of SphK activity or expression strongly suppressed the replication of influenza virus, revealing the proviral action of SphK. Further, inhibitors of SphK altered influenza virus-induced cellular signalling pathways that are crucial for efficient viral replication. Collectively, our findings demonstrate that regulation of S1P lyase and SphK could potently suppress influenza virus propagation and thus these enzymes represent novel cellular targets for the treatment of influenza virus infection.

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