WSSV exploits AMPK to activate mTORC2 signaling for proliferation by enhancing aerobic glycolysis

Abstract

AMPK plays significant roles in the modulation of metabolic reprogramming and viral infection. However, the detailed mechanism by which AMPK affects viral infection is unclear. The present study aims to determine how AMPK influences white spot syndrome virus (WSSV) infection in shrimp (Marsupenaeus japonicus). Here, we find that AMPK expression and phosphorylation are significantly upregulated in WSSV-infected shrimp. WSSV replication decreases remarkably after knockdown of Ampkα and the shrimp survival rate of AMPK-inhibitor injection shrimp increases significantly, suggesting that AMPK is beneficial for WSSV proliferation. Mechanistically, WSSV infection increases intracellular Ca2+ level, and activates CaMKK, which result in AMPK phosphorylation and partial nuclear translocation. AMPK directly activates mTORC2-AKT signaling pathway to phosphorylate key enzymes of glycolysis in the cytosol and promotes expression of Hif1α to mediate transcription of key glycolytic enzyme genes, both of which lead to increased glycolysis to provide energy for WSSV proliferation. Our findings reveal a novel mechanism by which WSSV exploits the host CaMKK-AMPK-mTORC2 pathway for its proliferation, and suggest that AMPK might be a target for WSSV control in shrimp aquaculture.

Unveiling the Role of Adenosine Monophosphate-Activated Protein Kinase (AMPK) Signaling in Managing Energetic and Metabolic Responses to Cu(OH)2 Nanopesticide in Zebrafish

“…27 AMPKinduced glycolytic flux has also been considered as a response to oxidative stress and the energy requirement. 28,29 AMPK Signaling Pathway and KEGG Enrichment Pathway. Since AMPK is hypothesized to regulate the energy metabolism in zebrafish exposed to Cu(OH) 2 nanopesticide, Western blotting was performed for AMPK and p-AMPK to confirm their roles.…”

“…AMPK activity has been demonstrated to be directly associated with glucose oxidation, glycolysis, and FFA oxidation . AMPK-induced glycolytic flux has also been considered as a response to oxidative stress and the energy requirement. , …”