Volume 43 Issue 1
Jan.  2022
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Wan-Wan Zhang, Peng Jia, Xiao-Bing Lu, Xiao-Qi Chen, Jue-Hua Weng, Kun-Tong Jia, Mei-Sheng Yi. Capsid protein from red-spotted grouper nervous necrosis virus induces incomplete autophagy by inactivating the HSP90ab1-AKT-MTOR pathway. Zoological Research, 2022, 43(1): 98-110. doi: 10.24272/j.issn.2095-8137.2021.249
Citation: Wan-Wan Zhang, Peng Jia, Xiao-Bing Lu, Xiao-Qi Chen, Jue-Hua Weng, Kun-Tong Jia, Mei-Sheng Yi. Capsid protein from red-spotted grouper nervous necrosis virus induces incomplete autophagy by inactivating the HSP90ab1-AKT-MTOR pathway. Zoological Research, 2022, 43(1): 98-110. doi: 10.24272/j.issn.2095-8137.2021.249

Capsid protein from red-spotted grouper nervous necrosis virus induces incomplete autophagy by inactivating the HSP90ab1-AKT-MTOR pathway

doi: 10.24272/j.issn.2095-8137.2021.249
Funds:  This study was supported by the Pearl River S&T Nova Program of Guangzhou (201806010047), National Natural Science Foundation of China (32173001, 3210284, 31771587), China Postdoctoral Science Foundation Funded Project (2021M693678), and Natural Science Foundation of Guangxi Province (2021GXNSFDA075015)
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  • 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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