RNA Helicase DDX3 Interacts with the Capsid Protein of Hepatitis E Virus and Plays a Vital Role in the Viral Replication

DDX3 is an ATP-dependent RNA helicase that is involved in multiple cellular activities, including RNA metabolism and innate immunity. DDX3 is known to assist the replication of some viruses while restricting others through its direct interaction with viral proteins. However, the role of DDX3 in the replication of the hepatitis E virus (HEV) is unknown. In this study, DDX3 was shown to interact with the HEV capsid protein and provide an important role in HEV replication. The DDX3 C-terminal domain was demonstrated to interact with the capsid protein. The depletion of DDX3 led to a significant reduction in HEV replication. Also, the ATPase motif of DDX3 was shown to be required in HEV replication as an ATPase-null mutant DDX3 failed to rescue the viral replication in the DDX3-depleted cells. These results demonstrate a pro-viral role of DDX3 in HEV replication, providing further insights on the virus-cell interactions.