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Brain Infection by Hepatitis E Virus Probably via Damage of the Blood-Brain Barrier Due to Alterations of Tight Junction Proteins

文献类型： 外文期刊

作者： Tian, Jijing 1 ; Shi, Ruihan 2 ; Liu, Tianlong 1 ; She, Ruiping 1 ; Wu, Qiaoxing 1 ; An, Junqing 1 ; Hao, Wenzhuo 1 ; Soo 1 ;

作者机构： 1.China Agr Univ, Coll Vet Med, Minist Agr, Lab Anim Pathol & Publ Hlth,Key Lab Zoonosis, Beijing, Peoples R China

2.Beijing Acad Agr & Forestry Sci, Inst Anim Husb & Vet Med, Beijing, Peoples R China

关键词： Hepatitis E virus; pathological changes; blood-brain barrier; tight junction; human brain microvascular endothelial cells

期刊名称：FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY （ 影响因子：5.293； 五年影响因子：5.882 ）

ISSN： 2235-2988

年卷期： 2019 年 9 卷

页码：

收录情况： SCI

摘要： Extrahepatic injury, particularly neurologic dysfunctions such as Guillain-Barre syndrome, neurologic amyotrophy, and encephalitis/meningoencephalitis/myositis were associated with HEV infection, which was supported by both clinical and laboratory studies. Thus, it is crucial to figure out how the virus invades into the central nervous system (CNS). In this study, CNS lesions were determined in rabbits and Mongolian gerbils inoculated with genotype 4 HEV. Junctional proteins were detected in HEV infected primary human brain microvascular cells (HBMVCs). Viral encephalitis associated perivascular cuffs of lymphocytes and microglial nodules were observed in HEV infected rabbits. Both positive-and negative-strand of HEV RNA was detected in brain and spinal cord in rabbits intraperitoneally infected with HEV at 28 dpi (days postinoculation), but not in rabbits gavaged with HEV. HEV ORF2 protein was further examined in both brain and spinal cord sections of infected rabbits, with positive signals located mainly in neural cells and perivascular areas. Ultrastructural study showed thickened and reduplicated basement membranes of capillary endothelium in HEV RNA positive brain tissues. In vitro study showed loss of tight junction proteins including Claudin5, Occludin, and ZO-1 (zonula occludens-1) in HBMVCs inoculated with HEV for 48 h. These findings indicated that disruption of the blood-brain barrier (BBB) might be potential mechanisms of HEV invasion into the CNS. It provides new insights to further study HEV associated neurologic disorders and will be helpful for seeking potential therapeutics for HEV infection in the future.

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