Dengue virus capsid interacts with DDX3X-a potential mechanism for suppression of antiviral functions in dengue infection

Kumar, R., Singh, N., Abdin, M. Z., Patel, A. H. and Medigeshi, G. R. (2018) Dengue virus capsid interacts with DDX3X-a potential mechanism for suppression of antiviral functions in dengue infection. Frontiers in Cellular and Infection Microbiology, 7, 542. (doi: 10.3389/fcimb.2017.00542) (PMID:29387631) (PMCID:PMC5776122)

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Abstract

Dengue virus is a pathogen of global concern and has a huge impact on public health system in low- and middle-income countries. The capsid protein of dengue virus is least conserved among related flavivirus and there is very limited information on the role of cytosolic proteins that interact with dengue virus capsid. We identified DEAD (Asp-Glu-Ala-Asp) Box Helicase 3, an X-Linked (DDX3X), cytosolic ATP-dependent RNA helicase as a dengue virus capsid-interacting protein. We show that the N-terminal region of capsid is important for interaction with DDX3X, while the N-terminal domain of DDX3X seems to be involved in interaction with dengue capsid. DDX3X was down-regulated in dengue virus infected cells at later stages of infection. Our results show that DDX3X is an antiviral protein as suppression of DDX3X expression by siRNA led to an increase in viral titers and overexpression of DDX3X led to inhibition of viral replication. Knock-down of DDX3X did not affect induction of type I interferon response upon infection suggesting that the effect of DDX3X knock-down is independent of the interferon-dependent pathways that DDX3X modulates under normal conditions. Thus, our study identifies DDX3X as a dengue virus capsid interacting protein and indicates a potential link between the antiviral functions of DDX3X and dengue capsid at later stages of dengue infection.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Patel, Professor Arvind
Authors: Kumar, R., Singh, N., Abdin, M. Z., Patel, A. H., and Medigeshi, G. R.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Frontiers in Cellular and Infection Microbiology
Publisher:Frontiers Research Foundation
ISSN:2235-2988
ISSN (Online):2235-2988
Copyright Holders:Copyright © 2018 Kumar, Singh, Abdin, Patel and Medigeshi
First Published:First published in Frontiers in Cellular and Infection Microbiology 7: 542
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
656491Basis of the host range and tissue tropism for hepatitis C virusArvind PatelMedical Research Council (MRC)MC_UU_12014/2MVLS III - CENTRE FOR VIRUS RESEARCH