Chinese Academy of Medical Sciences and University of Toronto, China
Title: Activation of the ubiquitin-like ISG15/USP18 signaling pathway contributes to interferon resistance of HCV and HBV
Biography: Limin Chen
Activation of the type-I interferon (IFN) signaling pathway poses the first line of defense against many virus infections, including HCV and HBV. Our previous work identified, using high throughput gene expression profiling, 18 differentially-expressed hepatic genes between treatment responders (Rs) and non-responders (NRs) to IFN treatment of patients chronically infected with HCV. 3 out of these 18 genes are involved in the same ubiquitin-like ISG15/USP18 signaling pathway, with higher expression levels in the pre-treatment liver tissues of NRs, indicating that activation of the ISG15/USP18 signaling contributes to treatment non-response leading to persistent infection. Similar findings were observed in chronic HBV infection. Mechanistically, some of these ISGs, such as ISG15 and ISG16 stimulated HCV replication and blunted IFN anti-HCV activity. All these data point out that type-I IFN signaling is a “double-edged” sword: while activation of this pathway is indeed necessary to control viral spread, over-activation of this pathway leading to the activation of the ISG15/USP18signaling actually benefits virus to facilitate its persistent infection.