Mechanisms of non-enveloped viral exit from the host

Viral exit from the host cell is a critical step of the viral lifecycle. Enveloped viruses have employed numerous mechanisms to exit their host including direct budding out of the plasma membrane, budding into the secretory pathway to be trafficked out, or budding into the endosomal membrane system to be exocytosed. Comparatively little is known about how non-enveloped RNA viruses such as Poliovirus (PV), Coxsackievirus B3 (CVB3), Rotavirus, Reovirus exit the host cell. Here I showed PV hijacks and diverts the host autophagy pathway to capture numerous virions in autophagosomes which are then trafficked by actin machinery to filopodial extensions and fuse with the plasma membrane to release infectious large vesicles containing mature polio virions. I also demonstrated the infectivity of the virus when inside a vesicle is higher then when free likely due to the vesicles containing many virions as the “clustered bombs”. Finally, I found the exported viral vesicles are highly enriched in phosphatidylserine lipids and that the infection on subsequent host cells is dependent on not only the poliovirus receptor but also the phosphotidylserine lipids on the vesicles. My findings suggest that non-enveloped viruses also carry a piece of the host with them on their pathogenic journey. The lipid and protein components within these membranes potentially modulate the pathogenesis of non-enveloped viruses within the host and provide a new paradigm for viral spread and tropism.Ph.D.Includes bibliographical referencesIncludes vitaby Ying-Han Che