microRNA-125a targets MAVS and TRAF6 to modulate interferon signaling and promote HCV infection

Hepatitis C virus (HCV) can cause chronic lifelong infections in humans, resulting in sustained hepatic inflammation, liver cirrhosis, and hepatocellular carcinoma. The clearance of HCV infections is dependent upon effective and coordinated innate and adaptive antiviral immune responses. However, HCV has evolved a range of strategies that enable it to evade or overcome the host immune response, enabling the virus to persist in susceptible hosts through mechanisms that remain to be fully clarified. Herein, we describe a novel mechanism whereby HCV can evade immune surveillance by activating microRNA (miR)-125a. Hepatocytes upregulate miR125a following HCV infection, and serum from HCV-infected patients similarly exhibits the upregulation of this miRNA. We found that miR-125a is able to target and suppress the expression of two key genes associated with the interferon (IFN) signaling pathway -mitochondrial antiviral signaling (MAVS) and TNF receptor-associated factor 6 (TRAF6). Disrupting the expression of these genes can in turn compromise type I IFN responses to HCV. Together, our data reveal that HCV infection results in the upregulation of miR-125a, which negatively regulates IFN signaling via inhibiting the expression of MAVS and TRAF6, thereby enabling the virus to evade innate antiviral immunity. Targeting this pathway may thus represent an efficient approach to treating HCV and bolstering antiviral immune responses in infected patients.

Automated summary

Hepatitis C virus can evade immune surveillance by activating miR-125a and suppressing interferon signaling pathway, allowing the virus to persist in hosts. Targeting this pathway may offer an efficient approach to treating HCV and boosting antiviral immune responses in infected patients.