Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

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

Version 1 : Received: 21 December 2020 / Approved: 22 December 2020 / Online: 22 December 2020 (12:19:32 CET)

How to cite: Lin, S.; Chang, P.; He, J.; Coyaud, E.; Pierce, B.; Zhang, Y. RNA Helicase DDX3 Interacts with the Capsid Protein of Hepatitis E Virus and Plays an Indispensable Role in the Viral Replication. Preprints 2020, 2020120557 (doi: 10.20944/preprints202012.0557.v1). Lin, S.; Chang, P.; He, J.; Coyaud, E.; Pierce, B.; Zhang, Y. RNA Helicase DDX3 Interacts with the Capsid Protein of Hepatitis E Virus and Plays an Indispensable Role in the Viral Replication. Preprints 2020, 2020120557 (doi: 10.20944/preprints202012.0557.v1).

Abstract

DDX3 is an ATP-dependent RNA helicase involved in multiple cellular activities, including RNA metabolism and innate immunity. DDX3 is known to assist the replication of some viruses while restricting some others through direct interaction with the viral proteins. However, the role of DDX3 in the replication of the hepatitis E virus (HEV) is unknown. In this study, DDX3 is shown to interact with the HEV capsid protein and provide an indispensable role in HEV replication. The DDX3 C-terminal domain was demonstrated to interact with the capsid protein, which was previously demonstrated to inhibit the production of type I interferons. Knockdown of DDX3 compromised the capsid protein-mediated blockage of interferon induction. Notably, DDX3 silencing led to a significant reduction in HEV replication. Also, the ATPase activity of DDX3 is required for the HEV replication as an ATPase-null mutant DDX3 failed to rescue the viral replication in the DDX3-silenced cells. These results demonstrate a pro-viral role of DDX3 in HEV replication, providing further insights into the virus-cell interactions.

Subject Areas

Hepatitis E virus (HEV); interferon (IFN); the capsid protein; DDX3; RNA helicase

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