title: Extra-hepatic replication and infection of hepatitis E virus in neuronal-derived cells.
abstract: Hepatitis E virus (HEV) is the causative agent of hepatitis E in humans and a member of the genus Orthohepevirus in 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 disorders such as Guillain-Barré syndrome, neuralgic amyotrophy and encephalitis. The pathogenesis of these neurological injuries remains 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 cycle in 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 Gaussia luciferase 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 oligodendrocytic cell line M03.13. In conclusion, these results indicate that HEV tropism is not restricted to the liver and HEV can potentially complete the full viral life cycle in neuronal-derived tissues explaining neurologic disorders during HEV infection.
authors.affiliation: Institute for Experimental Virology, TWINCORE, Centre for Experimental and Clinical Infection Research, A joint venture between the Medical School Hannover (MHH) and the Helmholtz Centre for Infection Research (HZI), Hannover, Germany.
authors.forename: S A
authors.initials: SA
authors.lastname: Drave
authors.affiliation: Department of Microbiology and Immunology, Rega Institute for Medical Research, KU Leuven, Leuven, Belgium.
authors.forename: Y
authors.initials: Y
authors.lastname: Debing
authors.affiliation: Institute for Experimental Virology, TWINCORE, Centre for Experimental and Clinical Infection Research, A joint venture between the Medical School Hannover (MHH) and the Helmholtz Centre for Infection Research (HZI), Hannover, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Walter
authors.affiliation: Institute for Experimental Virology, TWINCORE, Centre for Experimental and Clinical Infection Research, A joint venture between the Medical School Hannover (MHH) and the Helmholtz Centre for Infection Research (HZI), Hannover, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Todt
authors.affiliation: Institute for Experimental Virology, TWINCORE, Centre for Experimental and Clinical Infection Research, A joint venture between the Medical School Hannover (MHH) and the Helmholtz Centre for Infection Research (HZI), Hannover, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Engelmann
authors.affiliation: Institute for Experimental Virology, TWINCORE, Centre for Experimental and Clinical Infection Research, A joint venture between the Medical School Hannover (MHH) and the Helmholtz Centre for Infection Research (HZI), Hannover, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Friesland
authors.affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Wedemeyer
authors.affiliation: Department of Microbiology and Immunology, Rega Institute for Medical Research, KU Leuven, Leuven, Belgium.
authors.forename: J
authors.initials: J
authors.lastname: Neyts
authors.affiliation: Institute for Experimental Virology, TWINCORE, Centre for Experimental and Clinical Infection Research, A joint venture between the Medical School Hannover (MHH) and the Helmholtz Centre for Infection Research (HZI), Hannover, Germany.|Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Behrendt
authors.affiliation: Institute for Experimental Virology, TWINCORE, Centre for Experimental and Clinical Infection Research, A joint venture between the Medical School Hannover (MHH) and the Helmholtz Centre for Infection Research (HZI), Hannover, Germany.
authors.forename: E
authors.initials: E
authors.lastname: Steinmann
mesh_terms: D002460:Cell Line; D016752:Hepatitis E virus / Q000502:physiology*; D006801:Humans; D009457:Neuroglia / Q000821:virology*; D009474:Neurons / Q000821:virology*; D056189:Viral Tropism; D014779:Virus Replication
keywords: Hepatitis E Virus (HEV); extra-hepatic manifestation; neurologic disorders; neuronal-derived cells; ribavirin; viral replication