White Spot Syndrome Virus Establishes a Novel IE1/JNK/c-Jun Positive Feedback Loop to Drive Replication
Sheng Wang,
Haoyang Li,
Shaoping Weng,
Chaozheng Li,
Jianguo He
Affiliations
Sheng Wang
State Key Laboratory of Biocontrol/ Southern Marine Science and Engineering Guangdong Laboratory (Zhuhai), School of Marine Sciences, Sun Yat-sen University, Guangzhou, 510275, P. R. China; Guangdong Provincial Key Laboratory for Aquatic Economic Animals, School of Life Sciences, Sun Yat-sen University, Guangzhou, 510275, P. R. China
Haoyang Li
State Key Laboratory of Biocontrol/ Southern Marine Science and Engineering Guangdong Laboratory (Zhuhai), School of Marine Sciences, Sun Yat-sen University, Guangzhou, 510275, P. R. China; Guangdong Provincial Key Laboratory for Aquatic Economic Animals, School of Life Sciences, Sun Yat-sen University, Guangzhou, 510275, P. R. China
Shaoping Weng
State Key Laboratory of Biocontrol/ Southern Marine Science and Engineering Guangdong Laboratory (Zhuhai), School of Marine Sciences, Sun Yat-sen University, Guangzhou, 510275, P. R. China; Guangdong Provincial Key Laboratory for Aquatic Economic Animals, School of Life Sciences, Sun Yat-sen University, Guangzhou, 510275, P. R. China
Chaozheng Li
State Key Laboratory of Biocontrol/ Southern Marine Science and Engineering Guangdong Laboratory (Zhuhai), School of Marine Sciences, Sun Yat-sen University, Guangzhou, 510275, P. R. China; Guangdong Provincial Key Laboratory for Aquatic Economic Animals, School of Life Sciences, Sun Yat-sen University, Guangzhou, 510275, P. R. China; Guangdong Provincial Key Laboratory of Marine Resources and Coastal Engineering, Sun Yat-sen University, Guangzhou 510275, P. R. China; Corresponding author
Jianguo He
State Key Laboratory of Biocontrol/ Southern Marine Science and Engineering Guangdong Laboratory (Zhuhai), School of Marine Sciences, Sun Yat-sen University, Guangzhou, 510275, P. R. China; Guangdong Provincial Key Laboratory for Aquatic Economic Animals, School of Life Sciences, Sun Yat-sen University, Guangzhou, 510275, P. R. China; Guangdong Provincial Key Laboratory of Marine Resources and Coastal Engineering, Sun Yat-sen University, Guangzhou 510275, P. R. China; Corresponding author
Summary: Viruses need to hijack and manipulate host proteins to guarantee their replication. Herein, we uncovered that the DNA virus white spot syndrome virus (WSSV) established a novel positive feedback loop by hijacking the host JNK pathway via its immediate-early 1 (IE1) protein to drive replication. Specifically, the WSSV IE1 bound to host JNK, and enhanced JNK autoactivation by autophosphorylation, and in turn, elevated JNK kinase activity to its substrate c-Jun and induced IE1, which resulted in a viral gene-mediated positive feedback loop. Moreover, the activation of this loop is able to induce wsv056, wsv249, and wsv403, in addition to IE1 itself. Disruption of this loop during WSSV infection by knockdown of JNK, c-Jun or IE1 led to an increased survival rate and lower viral burdens in shrimp. Taken together, this loop may provide a potential target for the development of specific antiviral strategies or agents against WSSV infection. : Biological Sciences; Molecular Biology; Virology; Molecular Microbiology Subject Areas: Biological Sciences, Molecular Biology, Virology, Molecular Microbiology