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

Hepatitis B virus (HBV) infection causes acute and 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. Weshowthat collagen triple helix repeat containing1 (CTHRC1) expression is elevated in HBV-infected patientsand in HBV-transfected cells through epigenetic modification and transcriptional regulation. CTHRC1 facilitates HBV replication in cultured cells and BALB/c mice by activatingthe PKCa/ERK/JNK/c-Jun cascade to repressthe IFN/JAK/STAT pathway. HBV-activated CTHRC1 downregulatesthe activity of type I interferon (IFN),the production of IFN-stimulated genes (ISGs), and the phosphorylation of signal transducer and activator of transcription 1/2 (STAT1/2), whereas it upregulates the phosphorylation and ubiquitination of type IIFN receptors (IFNARa/b). 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. [ABSTRACT FROM AUTHOR]