| Virus Name | Hepatitis E virus |
| Virus Short Name | HEV |
| Order | Unassigned |
| Virus Family | Hepeviridae |
| Virus Subfamily | N.A. |
| Genus | Orthohepevirus |
| Species | Hepatitis E virus |
| Host | Human, pig, wild boar, monkey, some rodents, chicken |
| Cell Tropism | Intestinal tract, hepatocytes and cells in the biliary tract |
| Associated Disease | Hepatitis |
| Mode of Transmission | Zoonosis, fomite |
| VIPR DB link | https://www.viprbrc.org/brc/aboutPathogen.spg?decorator=hepe |
| ICTV DB link | https://talk.ictvonline.org/ictv-reports/ictv_9th_report/positive-sense-rna-viruses-2011/w/posrna_viruses/259/hepeviridae |
| Virus Host DB link | N.A. |
| Paper Title | Biological or pharmacological activation of protein kinase C alpha constrains hepatitis E virus replication |
| Author's Name | Wenshi Wang, Yijin Wang, Yannick Debing, Xinying Zhou, Yuebang Yin, Lei Xu, Elena Herrere Carrillo, Johannes H.Brandsma, Raymond A.Poot, Ben Berkhout, Johan Neyts,Maikel P.Peppelenbosch, Qiuwei Pan |
| Journal Name | Antiviral Research |
| Pubmed ID | 28077314 |
| Abstract | Although hepatitis E has emerged as a global health issue, there is limited knowledge of its infection biology and no FDA-approved medication is available. Aiming to investigate the role of protein kinases in hepatitis E virus (HEV) infection and to identify potential antiviral targets, we screened a library of pharmacological kinase inhibitors in a cell culture model, a subgenomic HEV replicon containing luciferase reporter. We identified protein kinase C alpha (PKCα) as an essential cell host factor restricting HEV replication. Both specific inhibitor and shRNA-mediated knockdown of PKCα enhanced HEV replication. Conversely, over-expression of the activated form of PKCα or treatment with its pharmacological activator strongly inhibited HEV replication. Interestingly, upon the stimulation by its activator, PKCα efficiently activates its downstream Activator Protein 1 (AP-1) pathway, leading to the induction of antiviral interferon-stimulated genes (ISGs). This process is independent of the JAK-STAT machinery and interferon production. However, PKCα induced HEV inhibition appears independent of the AP1 cascade. The discovery that activated PKCα restricts HEV replication reveals new insight of HEV-host interactions and provides new target for antiviral drug development. |
| Used Model | Huh7 and 293T cells |
| DOI | 10.1016/j.antiviral.2017.01.005 |
