Duck Tembusu virus induces incomplete autophagy via the ERK/mTOR and AMPK/mTOR signalling pathways to promote viral replication in neuronal cells
Duck Tembusu virus (DTMUV) is a neurotropic virus in the genus Flavivirus that causes massive economic losses to the poultry industry in China and neighbouring countries. Autophagy is pivotal in cellular responses to pathogens and in viral pathogenesis. However, little is known about the roles of au...
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Published in | Veterinary research (Paris) Vol. 54; no. 1; p. 103 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
England
BioMed Central Ltd
07.11.2023
BioMed Central BMC |
Subjects | |
Online Access | Get full text |
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Summary: | Duck Tembusu virus (DTMUV) is a neurotropic virus in the genus Flavivirus that causes massive economic losses to the poultry industry in China and neighbouring countries. Autophagy is pivotal in cellular responses to pathogens and in viral pathogenesis. However, little is known about the roles of autophagy in DTMUV replication and viral pathogenesis, especially in neuropathogenesis. In this study, mouse neuroblastoma cells (Neuro-2a) were used to establish a cell model of DTMUV infection. Our experiments indicated that DTMUV infection induced incomplete autophagy in Neuro-2a cells. Then, we used different autophagy regulators to alter the autophagy induced by DTMUV and found that incomplete autophagy promoted DTMUV replication. Furthermore, we showed that DTMUV infection activated the ERK and AMPK pathways, resulting in decreased phosphorylation of the autophagy repressor mTOR, subsequently leading to autophagic induction. In addition, we utilized ICR mice in an animal model of DTMUV infection to evaluate the autophagic responses in brain tissues and investigate the effects of autophagy on viral replication and tissue lesions. Our results confirmed that DTMUV induced incomplete autophagy in mouse brain tissues and that autophagy inducer treatment promoted DTMUV replication and aggravated DTMUV-induced lesions, whereas autophagy inhibitor treatment had the opposite effects. In summary, DTMUV infection induced incomplete autophagy through the ERK/mTOR and AMPK/mTOR signalling pathways to promote viral replication in mouse neuronal cells, and DTMUV-induced incomplete autophagy contributed to the neuropathogenesis of DTMUV. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1297-9716 0928-4249 1297-9716 |
DOI: | 10.1186/s13567-023-01235-0 |