Journal
ZOOLOGICAL RESEARCH
Volume 43, Issue 1, Pages 98-110Publisher
SCIENCE PRESS
DOI: 10.24272/j.issn.2095-8137.2021.249
Keywords
NNV; Autophagy; CP; HSP90ab1; AKT-MTOR pathway
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Funding
- Pearl River S&T Nova Program of Guangzhou [201806010047]
- National Natural Science Foundation of China [32173001, 3210284, 31771587]
- China Postdoctoral Science Foundation [2021M693678]
- Natural Science Foundation of Guangxi Province [2021GXNSFDA075015]
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This study found that red-spotted grouper NNV induces the formation of autophagosomes but impairs their fusion with lysosomes. It was discovered that the binding of NNV's capsid protein to the cell surface receptor HSP90ab1 contributes to the induction of autophagy. Furthermore, the study revealed that the capsid protein inhibits the interaction between HSP90ab1 and AKT, blocking the AKT-mTOR pathway.
As a highly important fish virus, nervous necrosis virus (NNV) has caused severe economic losses to the aquaculture industry worldwide. Autophagy, an evolutionarily conserved intracellular degradation process, is involved in the pathogenesis of several viruses. Although NNV can induce autophagy to facilitate infection in grouper fish spleen cells, how it initiates and mediates autophagy pathways during the initial stage of infection is still unclear. Here, we found that red-spotted grouper NNV (RGNNV) induced autophagosome formation in two fish cell lines at 1.5 and 3 h post infection, indicating that autophagy is activated upon entry of RGNNV. Moreover, autophagic detection showed that RGNNV entry induced incomplete autophagy by impairing the fusion of autophagosomes with lysosomes. Further investigation revealed that binding of the RGNNV capsid protein (CP) to the Lateolabrax japonicus heat shock protein HSP90ab1 (LjHSP90ab1), a cell surface receptor of RGNNV, contributed to RGNNV invasion-induced autophagy. Finally, we found that CP blocked the interaction of L. japonicus protein kinase B (AKT) with LjHSP90ab1 by competitively binding the NM domain of LjHSP90ab1 to inhibit the AKT-mechanistic target of the rapamycin (MTOR) pathway. This study provides novel insight into the relationship between NNV receptors and autophagy, which may help clarify the pathogenesis of NNV.
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