Dual-Role of Cholesterol‐25‐Hydroxylase in Regulating Hepatitis B Virus Infection and Replication
Qi Wei,
Hongxiao Song,
Yanli Gao,
Fengchao Xu,
Qingfei Xiao,
Fei Wang,
Bingxin Lei,
Junqi Niu,
Pujun Gao,
Haichun Ma,
Guangyun Tan
Affiliations
Qi Wei
Center for Pathogen Biology and Infectious Diseases, Department of Immunology, Key Laboratory of Organ Regeneration and Transplantation of the Ministry of Education, the First Hospital of Jilin University, Changchun, Jilin, China
Hongxiao Song
Center for Pathogen Biology and Infectious Diseases, Department of Immunology, Key Laboratory of Organ Regeneration and Transplantation of the Ministry of Education, the First Hospital of Jilin University, Changchun, Jilin, China
Yanli Gao
Department of Pediatrics, the First Hospital of Jilin University, Changchun, Jilin, China
Fengchao Xu
Center for Pathogen Biology and Infectious Diseases, Department of Immunology, Key Laboratory of Organ Regeneration and Transplantation of the Ministry of Education, the First Hospital of Jilin University, Changchun, Jilin, China
Qingfei Xiao
Department of Nephrology, the First Hospital of Jilin University, Changchun, Jilin, China
Fei Wang
Center for Pathogen Biology and Infectious Diseases, Department of Immunology, Key Laboratory of Organ Regeneration and Transplantation of the Ministry of Education, the First Hospital of Jilin University, Changchun, Jilin, China
Bingxin Lei
Department of Anesthesiology, the First Hospital of Jilin University, Changchun, Jilin, China
Junqi Niu
Center for Pathogen Biology and Infectious Diseases, Department of Immunology, Key Laboratory of Organ Regeneration and Transplantation of the Ministry of Education, the First Hospital of Jilin University, Changchun, Jilin, China
Pujun Gao
Department of Hepatology, The First Hospital of Jilin University, Changchun, Jilin, China
Haichun Ma
Department of Anesthesiology, the First Hospital of Jilin University, Changchun, Jilin, China
Guangyun Tan
Center for Pathogen Biology and Infectious Diseases, Department of Immunology, Key Laboratory of Organ Regeneration and Transplantation of the Ministry of Education, the First Hospital of Jilin University, Changchun, Jilin, China
ABSTRACT Hepatitis B virus (HBV)‐related diseases are among the major diseases that affect millions of people worldwide. These diseases are difficult to eradicate and thus pose a serious global health challenge. There is an urgent need to understand the cross talk mechanism between HBV and the host. Cholesterol‐25‐hydroxylase (CH25H) and its enzymatic product, 25‐hydroxycholesterol (25HC), were previously shown to exhibit effective broad‐spectrum antiviral activity. However, the role of CH25H in the regulation of HBV infection and replication remains unclear. The present study reported increased expression of CH25H in HBV-infected patients compared to healthy subjects. Importantly, higher expression of CH25H expression was found to be associated with low HBV replication. Additionally, the present study aimed to identify CH25H mutants, which would lack hydroxylase activity but retain antiviral activity toward HBV infection and replication. Interestingly, it was observed that both CH25H and its mutants interacted with HBx protein and inhibited nuclear translocation of HBx. In particular, CH25H interacted with the C-terminal region of HBx, while transmembrane region 3 of CH25H was found to be critical for CH25H–HBx interaction and inhibition of HBV replication. The study results suggested that 25HC promoted HBV infection but not HBV replication. Thus, the results of the present study suggested the involvement of a dual mechanism in CH25H-mediated regulation of HBV replication. The study clearly demonstrated cross talk between HBV and the host through CH25H–HBx axis. IMPORTANCE The enzymatic product of CH25H, 25-hydroxycholesterol (25HC), has been previously shown to play a critical role in the blockage of the cell-virus fusion in response to viral infection. However, our study indicates a dual role of CH25H in regulating HBV. We find the CH25H-mediated inhibition of HBV replication is independent on its enzyme activity and CH25H binds to HBx and inhibits HBx nucleus translocation. We are interested to find out 25HC promotes HBV infection.
