@article{Todt19012016, 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. HEV infections are the common cause of acute hepatitis but can also take chronic courses. Ribavirin is the treatment of choice for most patients and type I interferon (IFN) has been evaluated in a few infected transplantation patients in vivo. In this study, the antiviral effects of different exogenously administered interferons were investigated by using state-of-the-art subgenomic replicon and full-length HEV genome cell culture models. Hepatitis C virus (HCV) subgenomic replicons based on the genotype 2a JFH1 isolate served as reference. The experiments revealed that HEV RNA replication could be inhibited by the application of all types of IFN including IFN-α (type-I), -γ (type-II), and -λ3 (type-III), but to a far lesser extent as compared to HCV. Simultaneous determination of interferon stimulated genes (ISGs) expression levels for all IFN types demonstrated an efficient down-regulation by HEV. Furthermore, different IFN-α subtypes were able to block viral replication also in combination with ribavirin. The IFN-α subtypes 2a and 2b exerted the strongest antiviral activity against HEV. In conclusion, these data demonstrates for the first time moderate anti-HEV activities of type –II and –III IFNs and different IFN-α subtypes. As HEV employed a potent anti-interferon mechanism by restricting ISG expression, exogenous application of IFNs as immunotherapy should be carefully assessed.}, added-at = {2016-02-02T12:43:01.000+0100}, author = {Todt, D. and Francois, C. and Kusuma, A and Behrendt, P and Engelmann, M and Knegendorf, L and Vieyres, G and Wedemeyer, H and Hartmann, R and Pietschmann, T and Duverlie, G and Steinmann, E}, biburl = {https://www.bibsonomy.org/bibtex/20a0076b07e24f6d265087929d3df7c65/pietschmann}, editor = {Chemother, Antimicrob Agents}, interhash = {f34b17b91dd6a60ff2810bd9de4a1326}, intrahash = {0a0076b07e24f6d265087929d3df7c65}, journal = {Antimicrobial Agents and Chemotherapy}, keywords = {pietschmann}, number = 4, pages = {2132-2139}, pubmedurl = {http://www.ncbi.nlm.nih.gov/pubmed/26787701}, timestamp = {2016-04-06T12:25:14.000+0200}, title = {Antiviral activity of different interferon (sub-) types against hepatitis E virus replication}, volume = 60, year = 2016 }