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-1 beta 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-1 beta 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.

戊型肝炎病毒(HEV)是单股正链RNA病毒,主要经粪口途径在人和动物间传播.HEV感染已经成为全球性的公共卫生问题,多流行于卫生条件较差的地区.尽管HEV感染多为自限性,但仍有较高几率导致孕妇以及妊娠动物发生流产甚至死亡,并且越来越多的证据表明其可导致诸如神经系统症状等在内的肝外损伤.HEV作为一种人畜共患病原,具有广泛的宿主适应性,对猪、兔等经济动物的健康造成了较大威胁,同时也危害人类动物性食品安全,因此,有关HEV流行和感染机制的研究成为公共卫生和医学领域的热点问题.近年,随着HEV体外培养和动物模型探索成果的相继问世,HEV的生活史及其致病机制也有了新的研究进展.本文综合近年来HEV相关的研究进展,对其流行病学、分类、致病机制、研究模型以及面临的问题等进行简要阐述.

The hepatitis E virus (HEV) is an important pathogen that threatens global public health. One-third of the world’s population lives in the epidemic area of HEV, causing 20 million infections and 70,000 deaths annually. In China, HEV transmission has changed from human-to-human transmission of HEV1 to zoonotic transmission of HEV4, causing hepatitis outbreaks throughout the country. Protecting vulnerable groups, such as practitioners related to animal husbandry and downstream consumers who are immune deficient or pregnant, from HEV infections is an urgent task. At present, the commercial human vaccine, Hecolin® (HEV 239 vaccine), is licensed for use only in China. HEV 239 vaccine is a human vaccine developed for HEV1. Although it has a cross-protective effect on HEV4, the level of immune protection is still different. To address the transformation of domestic HEV transmission modes, there is an urgent need to develop a new vaccine against zoonotic HEV4. P206@PLGA is a vaccine candidate in which nanomaterials are used to encapsulate viral capsid proteins for the immunization of livestock animals. Our experiments show that P206@PLGA has excellent biocompatibility and safety. In addition, P206@PLGA can effectively induce animals to produce a high titer of antibodies against HEV4, and thus has the potential to become a veterinary vaccine for the prevention of HEV. This approach provides a new concept for HE prevention to reduce the transmission of HEV in farms and protect susceptible populations.

芳香烃受体(Aryl hydrocarbon receptor,AhR)是一种配体依赖性的转录蛋白,其广泛分布于人和动物的各种组织和细胞,且在不同生物体内其蛋白结构具有高度保守性.目前研究证实,AhR的配体主要分为两类,一类是外源性配体如二噁英,另一类为内源性配体,主要为色氨酸代谢产物[1].非激活状态下,AhR主要位于细胞质中,与热休克蛋白90、X-相关蛋白2和p23等结合形成复合物;当与其配体结合后,AhR即从复合物中解离,进入细胞核,并与核中的AhR核转运蛋白(AhR nuclear transloca-tor,ARNT)结合形成异二聚体,调节细胞色素酶P4501A1(Cytochrome P4501A1,CYP1A1)等多个下游基因的转录表达,参与机体的解毒作用[2].

戊型肝炎病毒(Hepatitis E virus,HEV)是一种重要的人兽共患病病原,在全球范围内广泛流行.猪是HEV的重要自然宿主,自然感染率较高,通常为亚临床感染或与其他病原混合感染.HEV主要通过粪口途径在人和动物之间传播,国内外均可见人群HEV聚集性感染的报道.由此可见,HEV的流行不仅对畜牧业生产造成威胁,还严重危害人类的食品安全.因此,了解猪群HEV的流行情况和防控措施具有重要的公共卫生学意义.本文调研近年来HEV相关的研究进展,对HEV在猪群中的流行情况、传播方式、诊断和防控等方面展开论述.