Absence of autophagy promotes apoptosis by modulating the ROS-dependent RLR signaling pathway in classical swine fever virus-infected cells

Jingjing Pei, Jieru Deng, Zuodong Ye, Jiaying Wang, Hongchao Gou, et al.

Autophagy 12(10), 1738-1758. 2016

Speaker: Zi-Yi Lu (呂姿儀)                                  Time: 15:00-16:00 Apr. 26, 2017

Commentator: Dr. Yao Chang (張堯 老師)        Place: Room 601

Abstract:

Classical swine fever virus (CSFV), which is an enveloped and positive-single strand RNA virus, belongs to Pestivirus within the Flavivridae family. With CSFV infection, the host might get classical swine fever (CSF), hemorrhages and even death. Although it has been known that under CSFV infection, viral replication will interfere type I interferon (IFN) production and apoptosis [1], the detailed mechanism of how CSFV inhibits apoptosis is still unclear. From authors’ previous study, they showed that autophagy is required for CSFV replication [2]. Recently there are more and more studies showing the crosstalk between autophagy and apoptosis. According to these former studies, authors tried to understand whether CSFV-induced autophagy inhibits apoptosis to enhance viral replication. First, they found that knockdown of the essential autophagy proteins, beclin-1 or LC3, in CSFV-infected cells was able to trigger intrinsic and extrinsic apoptosis. They also noticed that during CSFV infection, the increasing RIG-I-like receptor (RLR) signal occurred and promoted IFN production, which lead autophagy-impaired cells to extrinsic apoptosis. Furthermore, the accumulation of reactive oxygen species (ROS) was highly related not only to extrinsic apoptosis, which enhances RLR signal, but also to intrinsic apoptosis in autophagy-deficient cells. Taken all together, this study provide a new insight that for viral replication, CSFV will activate autophagy to prevent cell from apoptosis through suppressing ROS dependent RLR signal to persistent infect its host.

References:

1     Bensaude, E. et al. Classical swine fever virus induces proinflammatory cytokines and tissue factor expression and inhibits apoptosis and interferon synthesis during the establishment of long-term infection of porcine vascular endothelial cells. J Gen Virol 85(4), 1029-1037. 2004

2     Pei, J. et al. Autophagy enhances the replication of classical swine fever virus in vitro. Autophagy 10(1), 93-110. 2014