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 re...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.展开更多
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).
文摘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.
