MicroRNA-548j inhibits type I interferon production by targeting ZBTB11 in patients with chronic hepatitis B.
Type I IFNs play crucial roles in antiviral immune responses. By inducing cellular resistance to viral infection and apoptosis of virus-infected cells, they impair virus replication and eliminate the invading pathogens. However, in CHB patients, generation of type I IFN was significantly impaired and the underlying mechanisms have not been fully understood. MicroRNA-548 family has been implicated in regulating antiviral response upon various infections. Here we explored the potential role of miR-548j in modulating type I IFN production in CHB. We found that miR-548j expression increased in MoDCs from CHB patients than that from healthy volunteers and transient transfection of miR-548j mimic led to a marked decrease of IFN-α/β production in MoDCs from healthy volunteers while blockade of miR-548j by anti-miR-548j significantly restored IFN-α/β secretion in MoDCs from CHB patients. In addition, Zinc finger and BTB domain containing 11 (ZBTB11) was predicted and finally confirmed to be a target of miR-548j. Forced expression of ZBTB11 also restored IFN-α/β secretion in MoDCs from CHB patients. These results indicate the involvement of miR-548j in aberrant production of type I IFN in CHB patients, and provide a potential target for developing anti-HBV therapies.
Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai 200040, China.
Kangkang
K
Yu
Department of General Surgery, Qingdao Municipal Hospital, Qingdao 266071, China.
Qian
Q
Li
Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai 200040, China.
Qi
Q
Cheng
Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai 200040, China.
Chong
C
Huang
Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai 200040, China.
Jianming
J
Zheng
Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai 200040, China.
Shengsen
S
Chen
Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai 200040, China.
Qingxia
Q
Ling
Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai 200040, China.
Mengqi
M
Zhu
Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai 200040, China.
Mingquan
M
Chen
Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai 200040, China.
Guangfeng
G
Shi
Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai 200040, China. Electronic address: lining_hs@fudan.edu.cn.
Ning
N
Li
D002478:Cells, Cultured; D019694:Hepatitis B, Chronic / Q000235:genetics* / Q000378:metabolism / Q000628:therapy*; D006801:Humans; D007370:Interferon Type I / Q000096:biosynthesis* / Q000235:genetics; D035683:MicroRNAs / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism / Q000627:therapeutic use; D012097:Repressor Proteins / Q000096:biosynthesis / Q000235:genetics*
D007370:Interferon Type I; C561887:MIRN548 microRNA, human; D035683:MicroRNAs; D012097:Repressor Proteins
Chronic hepatitis B; Interferon; MicroRNA