Autophagy inhibitor treatment alleviates cerebral inflammatory responses in a mouse model of Japanese encephalitis

Abstract

Background Japanese Encephalitis (JE) is a zoonotic natural epidemic disease caused by Japanese Encephalitis Virus (JEV) infection. Currently, there is no specific medicine for Japanese encephalitis. Autophagy is a lysosomal degradation process that plays an important role in viral infection and cellular immunity. In vitro studies have shown that the Japanese encephalitis virus replication mechanism is related to the autophagy pathway. We hope that by studying the effects of autophagy-regulating drugs on JEV infection and host response in mice, will provide effective clinical trials for autophagy-regulating drugs in the treatment of Japanese encephalitis and other viral infectious diseases. Methods After establishing appropriate animal model. We observed the neurological symptoms of the mice and counted their survival rate. We observed histopathological changes in brain tissues of mice. We compared the extent of neuroinflammatory responses in the brain of mice and explored the signaling processes involved in neuroinflammation. Results We found autophagy inhibitors wortmannin (Wort) and chloroquine (CQ) slow down the occurrence of neurological symptoms and reduce the prevalence of JEV-infected mice. As expected, autophagy inhibitors can inhibit the activation of the PI3K/AKT/NF-kB pathway to alleviate cerebral inflammatory responses in mice, thereby protecting the mice from JEV-induced death. Conclusions Our study suggests that autophagy inhibitors wortmannin and chloroquine could attenuate the inflammatory response in the brain of JEV infected mice, providing a clinical basis for the treatment of Japanese encephalitis

Duck Tembusu virus induces incomplete autophagy via the ERK/mTOR and AMPK/mTOR signalling pathways to promote viral replication in neuronal cells

“…The viral load in the mouse brain tissues in the 3-MA + AQ-19 group was lower than that in the AQ-19 and RAPA + AQ-19 groups, and the histopathological changes in brain tissues in the 3-MA + AQ-19 group were slight compared with those in the AQ-19 and RAPA + AQ-19 groups. Similarly, autophagy inhibitors could reduce JEV infection and weaken the neurological signs and pathological changes in mouse brains, indicating the positive role of autophagy in the pathogenesis of JEV infection [43]. However, in WNV infection, inhibition of autophagy through AMPK degradation induces the accumulation of protein aggregates in the brains of mice, contributing to the development of neurological disease [20].…”