DnaJ homolog Hdj2 Facilitates Japanese Encephalitis Virus Replication
1 Department of Biomedical Sciences, Chang Gung University; Tao Yuan 33302, Taiwan, ROC
2 Research Center for Emerging Viral Infections, Chang Gung University, Tao Yuan 33302, Taiwan, ROC
3 Institute of Biotechnology and Department of Life Science, National Dong Hwa University, Hualien 97401, Taiwan, ROC
Virology Journal 2011, 8:471 doi:10.1186/1743-422X-8-471Published: 14 October 2011
Japanese encephalitis virus (JEV) is a member of the mosquito-borne Flaviviridae family of viruses that causes human encephalitis. Upon infection of a new host, replication of viral RNA involves not only the viral RNA-dependent RNA polymerase (RdRp), but also host proteins. Host factors involved in JEV replication are not well characterized.
We identified Hdj2, a heat-shock protein 40 (Hsp40)/DnaJ homolog, from a mouse brain cDNA library interacting with JEV nonstructural protein 5 (NS5) encoding viral RdRp using yeast two-hybrid system. Specific interaction of Hdj2 with NS5 was confirmed by coimmunoprecipitation and colocalization in JEV-infected cells. Overexpression of Hdj2 in JEV-infected cells led to an increase of RNA synthesis, and the virus titer was elevated approximately 4.5- to 10-fold. Knocking down of Hdj2 by siRNA reduced the virus production significantly.
We conclude that Hdj2 directly associates with JEV NS5 and facilitates viral replication. This study is the first to demonstrate Hdj2 involved in JEV replication, providing insight into a potential therapeutic target and cell-based vaccine development of JEV infection.