Potential capacity of interferon-α to eliminate covalently closed circular DNA (cccDNA) in hepatocytes infected with hepatitis B virus

Gut Pathogens

Guojun Li¹  Junwei Shao²  Chunhong Huang²  Jingwen Deng²  Gang Wang²  Nazif U. Khan²  Jun Guan²  Qihui Zhou²  Lichen Xu²  Zhi Chen²  Haihong Zhu² 

[1] Institute for Hepatology, Shenzhen Third People’s Hospital, National Clinical Research Center for Infectious Disease, 518112, Shenzhen, Guangdong, China;The Second Affiliated Hospital, School of Medicine, Southern University of Science and Technology, 518112, Shenzhen, China;State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, National Clinical Research Center for Infectious Diseases, Zhejiang University School of Medicine, 79 Qingchun Road, 310003, Hangzhou, Zhejiang, China;

关键词: Hepatitis B virus;    interferon-α;    Covalently closed circular DNA (cccDNA);    Chronic HBV infection;    Deamination;   

DOI  :  10.1186/s13099-021-00421-9

来源: Springer

【 摘 要 】

Interferon-alpha (IFN-α) and nucleot(s)ide analogs (NAs) are first-line drugs for the treatment of chronic hepatitis B virus (HBV) infections. Generally, NAs target the reverse transcription of HBV pregenomic RNA, but they cannot eliminate covalently-closed-circular DNA (cccDNA). Although effective treatment with NAs can dramatically decrease HBV proteins and DNA loads, and even promote serological conversion, cccDNA persists in the nucleus of hepatocytes due to the lack of effective anti-cccDNA drugs. Of the medications currently available, only IFN-α can potentially target cccDNA. However, the clinical effects of eradicating cccDNA using IFN-α in the hepatocytes of patients with HBV are not proficient as well as expected and are not well understood. Herein, we review the anti-HBV mechanisms of IFN-α involving cccDNA modification as the most promising approaches to cure HBV infection. We expect to find indications of promising areas of research that require further study to eliminate cccDNA of HBV in patients.

【 授权许可】

CC BY