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MAP3K15 facilitates multiple viral genes expression in crustaceans via Dorsal-CC-CL-STAT axis besides the JNK/P38

Xiao-Qin Ran1, Chen-Chen Liu1, Xue-Mei Xu1

  • 1Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Sciences, Shandong University, Qingdao, Shandong, China.

Plos Pathogens
|August 1, 2025
PubMed

Insights

Shrimp MAP3K15 (apoptosis signal-regulated kinase 3, ASK3) activates during white spot syndrome virus (WSSV) infection, promoting viral gene expression. Inhibiting MAP3K15 effectively controls WSSV in crustaceans.

Area of Science:

  • Molecular Biology
  • Virology
  • Immunology

Background:

  • The mitogen-activated protein kinase (MAPK) pathway is crucial for cellular responses to external signals.
  • While various MAPK kinase kinases (MAP3Ks) are involved in pathogen response, the role of MAP3K15 (apoptosis signal-regulated kinase 3, ASK3) in viral infections remains largely unexplored.

Purpose of the Study:

  • To investigate the function and mechanism of MAP3K15 during DNA virus (white spot syndrome virus, WSSV) infection in crustaceans.
  • To explore potential therapeutic strategies targeting MAP3K15 for WSSV control in aquaculture.

Main Methods:

  • Phosphorylation and activation assays of shrimp MAP3K15 during WSSV infection.
  • Co-immunoprecipitation to study interactions between MAP3K15 and Dorsal (NF-κB homolog).
  • Analysis of gene expression (CC-CL, viral immediate early genes) and signaling pathway activation (JAK/STAT, JNK/P38).
  • Inhibition studies using MAP3K15 knockdown and a specific inhibitor (SDK1) to assess viral load and host survival.

Main Results:

  • Shrimp MAP3K15 is phosphorylated and activated upon WSSV infection.
  • Activated MAP3K15 interacts with Dorsal, promoting its nuclear translocation and subsequent expression of CC-CL and viral immediate early genes.
  • CC-CL activates the JAK/STAT pathway, further upregulating viral gene expression. JNK/P38 pathway activation also contributes to viral gene expression.
  • Suppression of MAP3K15 or inhibition of its active form significantly reduces viral amplification and improves host survival rates across various crustaceans.

Conclusions:

  • MAP3K15 plays a critical and conserved role in facilitating DNA virus (WSSV) infection by modulating host signaling pathways.
  • The study elucidates a novel mechanism involving MAP3K15, Dorsal, CC-CL, and JAK/STAT signaling in WSSV pathogenesis.
  • Targeting MAP3K15 presents a promising strategy for managing WSSV outbreaks in crustacean aquaculture.

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