Hepatitis B virus hijacks CTHRC1 to evade host immunity and maintain replication

HepatitisBvirus (HBV) infection causes acuteand chronic liver diseases, but is not directly cytopathic. Liver injury results from repeated attempts of the cellular immune response system to control the viral infection. Here, we investigate the roles of cellular factors and signaling pathways involved in the regulation of HBV replication to reveal the mechanism underlying HBV infection and pathogenesis. We show that collagen triple helix repeat containing 1(CTHRC1) expression is elevated in HBV-infected patients and in HBV-transfected cells through epigenetic modification and transcriptional regulation. CTHRC1 facilitates HBV replication in cultured cells and BALB/c mice by activating the PKC alpha/ERK/JNK/c-Jun cascade to repress the IFN/JAK/STAT pathway. HBV-activated CTHRC1 downregulates the activity of type I interferon(IFN), the production of IFN-stimulatedgenes (ISGs), and the phosphorylation of signal transducer and activator of transcription 1/2 (STAT1/2), whereas it upregulates the phosphorylation and ubiquitination of type I IFN receptors (IFNAR alpha/beta). Thus, our results show that HBV uses a novel mechanism to hijack cellular factors and signal cascades in order to evade host antiviral immunity and maintain persistent infection. We also demonstrate that CTHRC1 has a novel role in viral infection.