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

作　　者：Xiaoqing Zhao Lu Sun Ting Mu Jianying Yi Chaoqun Ma Hong Xie Min Liu Hua Tang 

机构地区：[1]Tianjin Life Science Research Center,Tianjin Key Laboratory of Inflammation Biology,Collaborative Innovation Center of Tianjin for Medical Epigenetics,Department of Pathogen Biology,School of Basic Medical Sciences,Tianjin Medical University,Tianjin 300070,China [2]Department of Laboratory Medicine,General Hospital,Tianjin Medical University,Tianjin 300070,China

出　　处：《Journal of Molecular Cell Biology》2020年第4期263-276,共14页分子细胞生物学报（英文版）

基　　金：This work was supported in part by the National Natural Science Foundation of China(91629302,81830094,81572790,31270818,and 81773002);the Natural Science Foundation of Tianjin(19JCZDJC35900 and 16JCYBJC42400).

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,HBVmiR-3 in exosomes facilitated the Ml 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.

关 键 词：hepatitis B virus HBV-miR-3 IFN M1 polarization IL-6 

分 类 号：R392[医药卫生—免疫学]