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

Jiasheng Pan; Xiaodong Li; Rongsong Li; Yin Chen; Fareed Uddin Memon; Kun Wu; Jianghao Hu; Xiaole Xie; Jianhao Deng; Rongting Xu; Kang Li; Chuanxi Zhang; Ling Tian

doi:10.1016/j.ijbiomac.2025.139884

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

Int J Biol Macromol. 2025 Jan 14:139884. doi: 10.1016/j.ijbiomac.2025.139884. Online ahead of print.

Authors

Jiasheng Pan¹, Xiaodong Li², Rongsong Li¹, Yin Chen¹, Fareed Uddin Memon¹, Kun Wu¹, Jianghao Hu¹, Xiaole Xie¹, Jianhao Deng¹, Rongting Xu¹, Kang Li³, Chuanxi Zhang⁴, Ling Tian⁵

Affiliations

¹ Guangdong Laboratory for Lingnan Modern Agriculture, Guangdong Provincial Key Laboratory of Agro-animal Genomics and Molecular Breeding, College of Animal Science, South China Agricultural University, Guangzhou 510642, China; Guangdong Provincial Sericulture and Mulberry Engineering Research Center, College of Animal Science, South China Agricultural University, Guangzhou 510642, China.
² Guangxi Key Laboratory of Sericulture Ecology and Applied Intelligent Technology, Guangxi Collaborative Innovation Center of Modern Sericulture and Silk, Hechi University, Hechi 546300, China.
³ Guangdong Provincial Key Laboratory of Insect Developmental Biology and Applied Technology, Institute of Insect Science and Technology & School of Life Sciences, South China Normal University, Guangzhou 510631, China; Guangmeiyuan R&D Center, Guangdong Provincial Key Laboratory of Insect Developmental Biology and Applied Technology, South China Normal University, Meizhou 514779, China.
⁴ State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, Key Laboratory of Biotechnology in Plant Protection of Ministry of Agriculture and Zhejiang Province, Institute of Plant Virology, Ningbo University, Ningbo 315211, China.
⁵ Guangdong Laboratory for Lingnan Modern Agriculture, Guangdong Provincial Key Laboratory of Agro-animal Genomics and Molecular Breeding, College of Animal Science, South China Agricultural University, Guangzhou 510642, China; Guangdong Provincial Sericulture and Mulberry Engineering Research Center, College of Animal Science, South China Agricultural University, Guangzhou 510642, China. Electronic address: [email protected].

PMID: 39818371
DOI: 10.1016/j.ijbiomac.2025.139884

Abstract

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.

Keywords: B. mori serine/threonine protein phosphatase 5; BmNPV protein kinase 1; BmTFEB; Dephosphorylation; Proliferation.