摘要：SummaryViruses 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 inducedIE1, which resulted in a viral gene-mediated positive feedback loop. Moreover, the activation of this loop is able to inducewsv056,wsv249, andwsv403, in addition toIE1itself. Disruption of this loop during WSSV infection by knockdown ofJNK,c-JunorIE1led 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.Graphical AbstractDisplay OmittedHighlights•Lvc-Jun promotes WSSVIE1induction via interacting with the promoter ofIE1gene•The interaction of IE1-LvJNK enhances the autophosphorylation of LvJNK•IE1 hijacks the JNK/c-Jun cascade to create a feedback loop to drive replication•wsv056,wsv249, andwsv403are also benefit from this positive feedback loopBiological Sciences; Molecular Biology; Virology; Molecular Microbiology
