Dual-Role of Cholesterol‐25‐Hydroxylase in Regulating Hepatitis B Virus Infection and Replication
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....
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| Language: | English |
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American Society for Microbiology
2022-06-01
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| Series: | mBio |
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| Online Access: | https://journals.asm.org/doi/10.1128/mbio.00677-22 |
| _version_ | 1811237362885197824 |
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| author | Qi Wei Hongxiao Song Yanli Gao Fengchao Xu Qingfei Xiao Fei Wang Bingxin Lei Junqi Niu Pujun Gao Haichun Ma Guangyun Tan |
| author_facet | Qi Wei Hongxiao Song Yanli Gao Fengchao Xu Qingfei Xiao Fei Wang Bingxin Lei Junqi Niu Pujun Gao Haichun Ma Guangyun Tan |
| author_sort | Qi Wei |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T12:23:07Z |
| format | Article |
| id | doaj.art-404ec2c2122e42459aba340fd805ee83 |
| institution | Directory Open Access Journal |
| issn | 2150-7511 |
| language | English |
| last_indexed | 2024-04-12T12:23:07Z |
| publishDate | 2022-06-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mBio |
| spelling | doaj.art-404ec2c2122e42459aba340fd805ee832022-12-22T03:33:14ZengAmerican Society for MicrobiologymBio2150-75112022-06-0113310.1128/mbio.00677-22Dual-Role of Cholesterol‐25‐Hydroxylase in Regulating Hepatitis B Virus Infection and ReplicationQi Wei0Hongxiao Song1Yanli Gao2Fengchao Xu3Qingfei Xiao4Fei Wang5Bingxin Lei6Junqi Niu7Pujun Gao8Haichun Ma9Guangyun Tan10Center 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, ChinaCenter 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, ChinaDepartment of Pediatrics, the First Hospital of Jilin University, Changchun, Jilin, ChinaCenter 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, ChinaDepartment of Nephrology, the First Hospital of Jilin University, Changchun, Jilin, ChinaCenter 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, ChinaDepartment of Anesthesiology, the First Hospital of Jilin University, Changchun, Jilin, ChinaCenter 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, ChinaDepartment of Hepatology, The First Hospital of Jilin University, Changchun, Jilin, ChinaDepartment of Anesthesiology, the First Hospital of Jilin University, Changchun, Jilin, ChinaCenter 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, ChinaABSTRACT 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.https://journals.asm.org/doi/10.1128/mbio.00677-22CH25H25HCHBVHBxhepatitis B virus |
| spellingShingle | Qi Wei Hongxiao Song Yanli Gao Fengchao Xu Qingfei Xiao Fei Wang Bingxin Lei Junqi Niu Pujun Gao Haichun Ma Guangyun Tan Dual-Role of Cholesterol‐25‐Hydroxylase in Regulating Hepatitis B Virus Infection and Replication mBio CH25H 25HC HBV HBx hepatitis B virus |
| title | Dual-Role of Cholesterol‐25‐Hydroxylase in Regulating Hepatitis B Virus Infection and Replication |
| title_full | Dual-Role of Cholesterol‐25‐Hydroxylase in Regulating Hepatitis B Virus Infection and Replication |
| title_fullStr | Dual-Role of Cholesterol‐25‐Hydroxylase in Regulating Hepatitis B Virus Infection and Replication |
| title_full_unstemmed | Dual-Role of Cholesterol‐25‐Hydroxylase in Regulating Hepatitis B Virus Infection and Replication |
| title_short | Dual-Role of Cholesterol‐25‐Hydroxylase in Regulating Hepatitis B Virus Infection and Replication |
| title_sort | dual role of cholesterol 25 hydroxylase in regulating hepatitis b virus infection and replication |
| topic | CH25H 25HC HBV HBx hepatitis B virus |
| url | https://journals.asm.org/doi/10.1128/mbio.00677-22 |
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