GPR143 directs virus-induced cell vacuolation via the MKK6–p38 pathway

Published: 10 September 2025| Version 2 | DOI: 10.17632/x9ms3fhc9f.2
Contributors:
Qing Wang, Jian Tao Liang, Xuehong He, Liyun Wei, Xu Yan, Yanghui Meng, Xiuru Zhu, Songli Qing, Huihong Zhao, Lian Gan, Jinhui Wu, Song Yong Gan, Qi Wei Qin

Description

Cytoplasmic vacuolization is observed in vertebrate cells following exposure to viral pathogens. Causing cytoplasmic vacuolization is a key step for many viruses to induce cell death, however, the mechanisms underlying cytoplasmic vacuolization are unclear. Nervous necrosis virus (NNV) induces pronounced cytoplasmic vacuoles in the brain during infection. G protein-coupled receptors (GPCRs) regulate autophagosomes and cause vacuolation. Here, we used grouper and red-spotted grouper NNV (RGNNV) as the model to investigate the role of GPCRs in mediating virus induced cellular vacuolation in the central nervous system. GPR143 enhanced RGNNV-induced cytoplasmic vacuolation through intracellular binding to the RGNNV capsid protein and influenced the binding of autophagosomes and lysosomes. RGNNV enhanced interactions between GPR143 and MKK6, which phosphorylated p38 mitogen-activated protein kinase, subsequently activating the mTOR pathway, augmenting the binding of autophagosomes and lysosomes, and causing cytoplasmic vacuolation. Our study adds a new pathway by which viruses cause vacuolation in vertebrates.

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Institutions

  • South China Agricultural University

Categories

Histology, Fluorescence Microscopy, Western Blot, Fluorescence in Situ Hybridization, Real-Time Polymerase Chain Reaction, Grouper Fish

Funders

  • the National Natural Science Foundation of China
    Grant ID: 42176103, U20A20102
  • the National Key Research and Development Program of China
    Grant ID: 2022YFD2400502
  • the Guangdong Provincial Natural Science Foundation
    Grant ID: 2022A1515012505
  • breeding technology of candidate species for Guangdong modern marine ranching
    Grant ID: 2024-MRB-00-001

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