The ER-Golgi transport of influenza virus through NS1-Sec13 association during virus replication

Abstract

ABSTRACT Influenza A virus is a respiratory virus that can cause complications such as acute bronchitis and secondary bacterial pneumonia. Drug therapies and vaccines are available against influenza, albeit limited by drug resistance and the non-universal vaccine administration. Hence there is a need for host-targeted therapies against influenza to provide an effective alternative therapeutic target. Sec13 was identified as a novel host interactor of influenza. As Sec13 is a member of the nuclear pore complex and coat protein complex II (COPII) vesicles, localization of both Sec13 and non-structural protein 1 (NS1) in the nucleus, endoplasmic reticulum (ER), COPII vesicles (ER-to-Golgi transport), and Golgi was studied during infection. Sec13 is associated with ER, COPII, and Golgi in infected lung epithelial cells and not the nucleus during PR8 infection. This observation would imply the functional role of Sec13 in the COPII vesicles (ER-to-Golgi transport). Moreover, the colocalization of NS1 and Sec13 were correlated at several time points of infection, indicating the function of Sec13 during influenza infection. Inhibiting the ER-to-Golgi transport and silencing Sec13 decreased viral titers, whereas overexpressing Sec13 increased viral titers. Hence, we propose that the ER-to-Golgi transport is an important pathway of viral replication and viral export, and specifically, Sec13 has a functional role in influenza replication and virulence. IMPORTANCE Influenza A virus is a respiratory virus that can cause complications such as acute bronchitis and secondary bacterial pneumonia. Drug therapies and vaccines are available against influenza, albeit limited by drug resistance and the non-universal vaccine administration. Hence there is a need for host-targeted therapies against influenza to provide an effective alternative therapeutic target. Sec13 was identified as a novel host interactor of influenza. Endoplasmic reticulum-to-Golgi transport is an important pathway of influenza virus replication and viral export. Specifically, Sec13 has a functional role in influenza replication and virulence.