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