Baculovirus protein kinase 1 activates AMPK-protein phosphatase 5 axis to hijack transcription factor EB for self-proliferation.

Baculovirus causes lethal nuclear polyhedrosis in insects, whereas its regulatory mechanism on host transcription has not been fully illustrated. Herein, Bombyx mori nucleopolyhedrovirus (BmNPV) infection caused dephosphorylation and thus cytoplasmic-nucleo translocation of transcription factor EB (BmTFEB) by inhibiting Mechanistic target of rapamycin complex 1 (MTORC1), while upregulating Adenosine monophosphate-activated protein kinase (AMPK) signaling to promote self-proliferation through the rival protein kinase 1 in Bombyx mori. Significantly, B. mori serine/threonine protein phosphatase 5, which leads to dephosphorylation of BmTFEB and its nuclear importation, was identified to interact with BmTFEB dependent of BmAMPK. Dephosphorylation at S117 and S324 sites in BmTFEB were the essential phosphorylation sites for mediating the cytoplasmic-nucleo translocation after BmNPV infection. Notably, BmTFEB upregulated the expressions of a set of metabolism-related genes to facilitate BmNPV proliferation, and BmTFEB knockout partly rescued larval survival. This study sheds light on the subtle interaction between NPV and the host, and provides a potential target for the utilization or control of the pathogen.