NLRP3 Inflammasome Activation Mediates Hepatitis E Virus‐Induced Neuroinflammation

• Published in: Journal of viral hepatitis 2024-11, Vol.31 (11), p.729-738
• Main Authors: Wei, Bingyan, Li, Huopeng, Cheng, Minheng, Yang, Yifei, Liu, Bo, Tian, Yuewei, Sun, Yaxin, Liu, Tianlong, She, Ruiping, Tian, Jijing
• Format: Article
• Language: English
• Subjects: Blood-brain barrier; brain; Brain injury; Caspase; Cell activation; Central nervous system; Endothelial cells; Gliosis; hBMECs; Hepatitis; hepatitis E virus; Infections; Inflammasomes; Inflammation; Microvasculature; Nervous system; Neurological diseases; NLRP3 inflammasome; Viruses
• ISSN: 1352-0504; 1365-2893; 1365-2893
• DOI: 10.1111/jvh.13998

ABSTRACT Hepatitis E virus (HEV) is a foodborne zoonotic pathogen that is supposed to be one of the most common causes of acute viral hepatitis. However, HEV infection has been recently associated with a wide spectrum of extrahepatic manifestations, particularly neurological disorders. Previous studies have shown that HEV is able to cross the blood–brain barrier (BBB) and induce inflammatory response of the central nervous system. However, the pathogenesis of HEV‐induced neuroinflammation and tissue injury of the central nervous system have yet to be fully elucidated. In this study, activation of NLRP3 inflammasome following HEV infection were investigated. In a gerbil model infected by HEV, brain histopathological changes including gliosis, neuronophagia and neuron injury were observed and expression of NLRP3, caspase‐1, IL‐1β and IL‐18 were elevated. Brain microvascular endothelial cells (BMECs) are key components of the BBB that protects the brain from various challenges. Following HEV infection, virus‐like particles range from 30 to 40 nm in diameter were observed in human BMECs (hBMECs). Enhanced expression levels of NLRP3 and subsequent ASC, caspase‐1, IL‐1β and IL‐18 were detected in infected cells. Treatment with MCC950 alleviated HEV infection induced activation of NLRP3 inflammasome, mitochondrial damage and VE‐cadherin degradation. The findings provide new insights into HEV‐associated neuroinflammation. Moreover, targeting NLRP3 inflammasome signalling is a promising therapeutic in HEV‐induced neurological disorder.