期刊
FISH & SHELLFISH IMMUNOLOGY
卷 98, 期 -, 页码 908-916出版社
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.fsi.2019.11.053
关键词
Grouper; Autophagy; LC3; RGNNV; Replication
资金
- National Key R&D Program of China [2018YFD0900501, 2018YFC0311302]
- China Agricultural Research System [CARS-47-G16]
- National Natural Science Foundation of China [31572643, 31772882]
- Open Fund of Key Laboratory of Experimental Marine Biology, Chinese Academy of Sciences [KF2018NO3]
- Science and Technology Planning Project of Guangdong Province, China [2015TQ01N118]
Autophagy is an evolutionarily conserved cellular degradation process that is essential for homeostasis. As a cell steward, autophagy is thought to be a process that may have evolved to combat intracellular pathogens. However, some virus can subvert or utilize autophagy-related membrane structures to increase viral replication. The red-spotted grouper nervous necrosis virus (RGNNV) is a fish pathogen which leads to disastrous viral nervous necrosis in larvae and juvenile groupers and other marine fishes. To better comprehend the pathogenesis and replication mechanism of RGNNV, we investigated the relationship between RGNNV and autophagy. Here, we demonstrated that RGNNV induced autophagy in grouper spleen (GS) cells, as the significant increase in ultrastructural autophagosome-like vesicles, fluorescent punctate pattern of microtubule-associated protein 1 light chain 3 (LC3), and the conversion of LC3-I to LC3-II. Additionally, ultraviolet-inactivated RGNNV and the capsid protein also triggered autophagy. Enhancement of autophagy contributed to RGNNV replication, whereas blocked autophagy decreased RGNNV replication. Moreover, impeded fusion of autophagosomes and lysosomes also reduced RGNNV replication, indicating that RGNNV utilized the different steps of autophagy pathway to facilitate viral replication. The further study showed that RGNNV induced autophagy through activating the phosphorylation of eIF2 alpha and inhibiting the phosphorylation of mTOR. These results will assist the search for novel drugs targets and vaccine design against RGNNV from the perspective of downregulating autophagy.
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