An HBV-encoded miRNA activates innate immunity to restrict HBV replication

• 来源期刊: 分子细胞生物学报（英文版）
• 年，卷（期）: 2020,（4）
• 页码范围: 263-276
• 页数: 14页
• 语种: 英文
• DOI: 10.1093/jmcb/mjz104

摘要

We previously identified that hepatitis B virus (HBV) encodes a microRNA (HBV-miR-3) that restrains HBV replication by targeting the HBV transcript.However,whether HBV-miR-3 affects host innate immunity to modulate HBV replication remains unclear.Here,we examined the vital functions of HBV-miR-3 in the innate immune response after HBV infection.We found that HBV-miR-3 expression gradually increased in a dose-and time-dependent manner in HBV-infected HepG2-NTCP cells.HBV-miR-3 activated the JAK/STAT signaling pathway by downregulating SOCS5 in hepatocytes,thereby enhancing the IFN-induced anti-HBV effect.In addition,HBV-miR-3 in exosomes facilitated the M1 polarization of macrophages.Furthermore,exosomes containing HBV-miR-3 enhanced the secretion of IL-6 via inhibiting the SOCS5-mediated ubiquitination of EGFR.In short,these results demonstrate that HBV-miR-3 activates the innate immune response to restrain HBV replication by multiple pathways,which may suppress HBV-induced acute liver cell injury and affect the progression of persistent HBV infection.