IDENTIFICATION AND CHARACTERIZATION OF SEC13 IN INFLUENZA INFECTION

Abstract

Influenza A virus is a respiratory virus which can cause complications such as acute bronchitis and secondary bacterial pneumonia. Due to viral adaptions, highly virulent strains may appear and develop into global pandemics such as the 1918 H1N1 Spanish pandemic and the 2009 H1N1 Swine flu. There is a vaccine and drug therapies available against influenza, but the current vaccine is not universal and there are occurrences of drug resistance with current therapies. Hence there is a need for host direct therapies against influenza that would provide an alternative method of targeting the virus. Using bioinformatics, yeast and mammalian cell models, Sec13 was identified as a novel host interactor of influenza. Sec13 was associated with ER, COPII and Golgi and not the nucleus during PR8 infection. This would imply the role of Sec13 in the COPII vesicles (ER-to-Golgi transport). Moreover, the localization of NS1 and Sec13 were correlated at different time points of infection. Inhibition of the ER-to-Golgi transport and Sec13 knockdown decreased viral titers whereas Sec13 overexpression increased viral titers. Hence, we propose that the ER-to-Golgi transport is an important pathway of viral replication and specifically Sec13 has a role in influenza replication.