期刊
VETERINARY MICROBIOLOGY
卷 230, 期 -, 页码 283-290出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.vetmic.2019.01.002
关键词
Fusion protein; Hemagglutinin-neuraminidase protein; Autophagy; Newcastle disease virus
资金
- National Key Research and Development Program of China [2018YFD0500100]
- National Natural Science Foundation of China [31530074, 31872453]
Autophagy triggered by glycoprotein-mediated membrane fusion has been reported for several paramyxoviruses. However, the function of HN and F glycoproteins of NDV and their role in autophagy induction have not been studied. Here, we found that co-transfection of HN and F of virulent NDV rapidly induced syncytium formation and triggered a steady state autophagy flux in adenocarcinomic human alveolar basal epithelial (A549) cells and chicken embryo fibroblast (DF-1) cells. Furthermore, we clearly identified that F and HN synergistically induced autophagosome fusion with lysosomes for subsequent degradation. The seven cleavage site mutations of F significantly decreased the autophagy induction, compared with those of wildtype virulent F. RNAi and pharmacological experiments suggested that autophagy benefitted membrane fusion and syncytium formation induced by F and HN of NDV. Activated F-1 co-operated with HN to stimulate AMPK kinase and downstream ULK1 activation to suppress mTORC1 signaling. Our data described the synergistic role of HN and F in the induction of completed autophagic flux through the activation of AMPK- mTORC1- ULK1 pathway.
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