Canine distemper virus N protein induces autophagy to facilitate viral replication

by Selleckchem | Jun 06 2023

Background: Canine distemper virus (CDV) is one of the most contagious and lethal viruses known to the Canidae, with a very broad and expanding host range. Autophagy serves as a fundamental stabilizing response against pathogens, but some viruses have been able to evade or exploit it for their replication. However, the effect of autophagy mechanisms on CDV infection is still unclear.

Results: In the present study, autophagy was induced in CDV-infected Vero cells as demonstrated by elevated LC3-II levels and aggregation of green fluorescent protein (GFP)-LC3 spots. Furthermore, CDV promoted the complete autophagic process, which could be determined by the degradation of p62, co-localization of LC3 with lysosomes, GFP degradation, and accumulation of LC3-II and p62 due to the lysosomal protease inhibitor E64d. In addition, the use of Rapamycin to promote autophagy promoted CDV replication, and the inhibition of autophagy by Wortmannin, Chloroquine and siRNA-ATG5 inhibited CDV replication, revealing that CDV-induced autophagy facilitated virus replication. We also found that UV-inactivated CDV still induced autophagy, and that nucleocapsid (N) protein was able to induce complete autophagy in an mTOR-dependent manner.

Conclusions: This study for the first time revealed that CDV N protein induced complete autophagy to facilitate viral replication.

Comments:

The study presented here provides new insights into the interaction between canine distemper virus (CDV) and the host autophagy machinery. The authors demonstrated that CDV infection induces autophagy in Vero cells, as evidenced by the increased levels of LC3-II and the aggregation of GFP-LC3 spots. Moreover, CDV was found to promote the complete autophagic process, as shown by the degradation of p62, co-localization of LC3 with lysosomes, GFP degradation, and accumulation of LC3-II and p62 upon treatment with the lysosomal protease inhibitor E64d.

Interestingly, the authors also found that CDV-induced autophagy facilitated virus replication, as the promotion of autophagy by Rapamycin increased CDV replication, while the inhibition of autophagy by Wortmannin, Chloroquine, and siRNA-ATG5 inhibited CDV replication. This suggests that CDV has evolved to exploit the autophagy pathway to enhance its own replication.

Furthermore, the authors demonstrated that the CDV N protein was able to induce complete autophagy in an mTOR-dependent manner, even in the absence of active virus particles. This highlights the importance of the N protein in CDV-induced autophagy and suggests that it may play a critical role in the virus life cycle.

Overall, this study provides new insights into the mechanisms underlying CDV infection and sheds light on the complex interplay between viruses and the host autophagy machinery. The findings may also have implications for the development of new antiviral therapies targeting the autophagy pathway.