Extra-hepatic replication and infection of hepatitis E virus in neuronal-derived cells

2016
Summary Hepatitis E virus(HEV) is the causative agent of hepatitis Ein humans and a member of the genus Orthohepevirusin the family Hepeviridae. Infection usually leads to acute hepatitis that can become fulminant, particularly among pregnant women and in patients with preexisting liver disease, or may evolve to a chronic state, especially in immunosuppressed individuals. HEV has been shown to produce a range of extra-hepatic manifestations including aplastic anaemia, acute thyroiditis, glomerulonephritis as well as neurological disorderssuch as Guillain-Barre syndrome, neuralgic amyotrophyand encephalitis. The pathogenesis of these neurological injuriesremains largely unknown, and it is also uncertain whether or not HEV can directly infect neuronal cells. In this study, we investigated whether HEV is capable of completing the viral life cyclein human neuronal-derived cell lines such as neuroepithelioma (SK-N-MC), desmoplastic cerebellar medulloblastoma(DAOY), glioblastoma multiforme (DBTRG), glioblastoma astrocytoma (U-373 MG) and oligodendrocytic(M03.13) cells. Following transfection of these cells with HEV Gaussialuciferase reporter virus, all tested cell lines supported HEV RNA replication. Furthermore, extra- and intracellular viral capsid was detected by an HEV antigen ELISA as a marker for virus assembly and release. Permissiveness for HEV cell entry could be demonstrated for the oligodendrocyticcell line M03.13. In conclusion, these results indicate that HEV tropismis not restricted to the liver and HEV can potentially complete the full viral life cyclein neuronal-derived tissues explaining neurologic disordersduring HEV infection.
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