An HBV-encoded miRNA activates innate immunity to restrict HBV replication. (21st December 2019)

• Record Type: Journal Article
• Authors: Zhao, Xiaoqing; Sun, Lu; Mu, Ting; Yi, Jianying; Ma, Chaoqun; Xie, Hong; Liu, Min; Tang, Hua
• Editors: Su, Bing
• Is Part Of: Journal of molecular cell biology. Volume 12:Number 4(2020)
• Page Start: 263
• Page End: 276
• Publication Date: 2019-12-21
• Subjects: hepatitis B virus -- HBV-miR-3 -- IFN -- M1 polarization -- IL-6; Molecular biology -- Periodicals; 571.605
• DOI: 10.1093/jmcb/mjz104
• Languages: English
• ISSNs: 1674-2788

Abstract

Abstract: 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.