Abstract
During infection, dengue virus (DENV) proteins interact with host cellular constituents promoting the remodeling of the cell to facilitate virus production. While a number of interacting proteins have been identified for DENV non-structural proteins, far fewer interacting partners have been identified for the DENV structural proteins. One protein that has been identified as a DENV E protein interacting protein is the cellular chaperone GRP78. GRP78 has been shown to have a number of cellular interacting partners including the voltage-dependent anion channel (VDAC). In this study we confirmed the interactions between GRP78 and DENV E protein and between GRP78 and VDAC. VDAC was shown to be re-localized during DENV infection, with no change in levels of protein expression. VDAC is predominantly located on the outer membrane of mitochondria and our result is consistent with movement of the mitochondria towards the ER during DENV infection. Down regulation of VDAC through siRNA significantly reduced DENV protein expression, as well as the percentage infection and output virus titer. Our results suggest that VDAC plays an important role in DENV infection.
Highlights
Despite the recent introduction of a vaccine[1] in a few countries, infections with the mosquito transmitted dengue virus (DENV) remain a significant worldwide public health problem
GRP78 is a multifunctional chaperone protein[17]. It is primarily resident in the ER where it mediates the induction of the unfolded protein response (UPR) through its interactions with three key proteins, namely IRE1 (Inositol-requiring protein 1), ATF6 (Activating transcription factor 6) and PERK18
This, coupled with our previous study showing an interaction between Japanese encephalitis virus (JEV) E protein and GRP78 in insect cells[27], suggests that this interaction might be a common interaction in flavivirus infections
Summary
Despite the recent introduction of a vaccine[1] in a few countries, infections with the mosquito transmitted dengue virus (DENV) remain a significant worldwide public health problem. During DENV replication the host cellular processes are manipulated to create a favorable environment for viral replication and assembly[10]. This is achieved through a number of mechanisms, but through the direct interaction of viral proteins with host cellular proteins to modulate their expression or activity[11,12]. This presupposes that viral protein possess other functions in addition to a direct role in viral replication or viral assembly. Only a few cytoplasmic interacting partners of DENV E protein have www.nature.com/scientificreports/
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
