title: Cutthroat trout virus as a surrogate in vitro infection model for testing inhibitors of hepatitis E virus replication.
abstract: Hepatitis E virus (HEV) is one of the most important causes of acute hepatitis worldwide. Although most infections are self-limiting, mortality is particularly high in pregnant women. Chronic infections can occur in transplant and other immune-compromised patients. Successful treatment of chronic hepatitis E has been reported with ribavirin and pegylated interferon-alpha, however severe side effects were observed. We employed the cutthroat trout virus (CTV), a non-pathogenic fish virus with remarkable similarities to HEV, as a potential surrogate for HEV and established an antiviral assay against this virus using the Chinook salmon embryo (CHSE-214) cell line. Ribavirin and the respective trout interferon were found to efficiently inhibit CTV replication. Other known broad-spectrum inhibitors of RNA virus replication such as the nucleoside analog 2'-C-methylcytidine resulted only in a moderate antiviral activity. In its natural fish host, CTV levels largely fluctuate during the reproductive cycle with the virus detected mainly during spawning. We wondered whether this aspect of CTV infection may serve as a surrogate model for the peculiar pathogenesis of HEV in pregnant women. To that end the effect of three sex steroids on in vitro CTV replication was evaluated. Whereas progesterone resulted in marked inhibition of virus replication, testosterone and 17β-estradiol stimulated viral growth. Our data thus indicate that CTV may serve as a surrogate model for HEV, both for antiviral experiments and studies on the replication biology of the Hepeviridae.
authors.affiliation: Rega Institute for Medical Research, Department of Microbiology and Immunology, Minderbroedersstraat 10, 3000 Leuven, Belgium.
authors.forename: Yannick
authors.initials: Y
authors.lastname: Debing
authors.forename: James
authors.initials: J
authors.lastname: Winton
authors.forename: Johan
authors.initials: J
authors.lastname: Neyts
authors.forename: Kai
authors.initials: K
authors.lastname: Dallmeier
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D005260:Female; D016751:Hepatitis E / Q000821:virology*; D016752:Hepatitis E virus / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D006801:Humans; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000821:virology*; D012328:RNA Viruses / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D012474:Salmon; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents
keywords: Antiviral; Cutthroat trout virus; Hepatitis E virus; Interferon; Pregnancy; Ribavirin