Autophagy Is a Potential Therapeutic Target Against Duck Tembusu Virus Infection in vivo

Abstract

Duck tembusu virus (DTMUV) is newly emerged in poultry and causes great losses to the breeding industry in China and neighboring countries. Effective antiviral strategies are still being studied. Autophagy is a cellular degradative pathway, and our lab's previous data show that autophagy promotes DTMUV replication in vitro. To study the role of autophagy further in vivo, we utilized ducks as the animal model to investigate the autophagy responses in DTMUV-targeted tissues. And also, we utilized autophagy regulators, including Rapamycin (Rapa) as the autophagy enhancer, 3-Methyladenine (3-MA) and Chloroquine (CQ) as the autophagy inhibitors, to adjust the host autophagic levels and then study the effects of autophagy on tissue damages and virus replication. As a result, we first found DTMUV infection trigged autophagy and autophagy regulator treatments regulated autophagy levels successfully in duck spleens and brains. Next, we found that autophagy inhibitors inhibited DTMUV replication and alleviated DTMUV-induced pathological symptoms, whereas the autophagy inducer treatment led to the opposite effects. And we also found that autophagic regulation was correlated with the expression of innate immune genes, including pattern recognition receptors, type I interferons, and cytokines, and caused different effects in different tissues. In summary, we demonstrated that autophagy facilitated DTMUV replication, aggravated the developments of pathological symptoms and possibly counteracts the host's innate immunity response in vivo.

The Protective Role of TLR2 Mediates Impaired Autophagic Flux by Activating the mTOR Pathway During Neospora caninum Infection in Mice

“…Treatment with the early autophagy inhibitor 3-MA controlled the proliferation of N. caninum, although there was no significant difference in survival rate between the coadministration of the 3-MA group and the N. caninum-infected group, which may be attributable to the complex physiological environments. Similar findings have been observed in the study of many other pathogenic microorganisms, such as T. cruzi (Romano et al, 2009), Plasmodium (Thieleke-Matos et al, 2016, mouse hepatitis virus (Prentice et al, 2004), and duck Tembusu virus (Hu et al, 2020). The results indicate that the formation of early autophagosomes has a facilitative effect on N. caninum proliferation; in contrast, the activation of autophagy rather than exerting an anti-infection effect promotes N. caninum infection.…”

New Insights into the Biology of the Emerging Tembusu Virus

“…Indeed, the p62 adaptor is not only a cargo adaptor but also an important player in the immune response via activation of the IFN and NF-kB pathways. p62 degradation may be a strategy developed by TMUV to evade innate immune responses [ 94 , 123 ].…”