干扰素-α消除感染乙型肝炎病毒的肝细胞中共价闭合环状DNA

StephenW

Potential capacity of interferon-α to eliminate covalently closed circular DNA (cccDNA) in hepatocytes infected with hepatitis B virus
Gang Wang  1 , Jun Guan  1 , Nazif U Khan  1 , Guojun Li  2   3 , Junwei Shao  1 , Qihui Zhou  1 , Lichen Xu  1 , Chunhong Huang  1 , Jingwen Deng  1 , Haihong Zhu  1 , Zhi Chen  4
Affiliations
Affiliations

    1
    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, Hangzhou, 310003, Zhejiang, China.
    2
    Institute for Hepatology, Shenzhen Third People's Hospital, National Clinical Research Center for Infectious Disease, Shenzhen, 518112, Guangdong, China.
    3
    The Second Affiliated Hospital, School of Medicine, Southern University of Science and Technology, 518112, Shenzhen, China.
    4
    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, Hangzhou, 310003, Zhejiang, China. [email protected].

    PMID: 33845868 PMCID: PMC8040234 DOI: 10.1186/s13099-021-00421-9

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Abstract

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.

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

StephenW

干扰素-α消除感染乙型肝炎病毒的肝细胞中共价闭合环状DNA（cccDNA）的潜在能力
王刚1，君官1，纳粹夫1，李国君2 3，邵俊伟1，周启辉1，徐立成1，黄春红1，邓景文1，朱海虹1，智臣4
隶属关系
隶属关系

    1个
    传染病诊断与治疗国家重点实验室，传染病诊断与治疗协同创新中心，医学院第一附属医院，浙江大学医学院国家传染病临床研究中心，杭州庆春路79号，310003，浙江，中国。
    2个
    国家传染病临床研究中心，深圳市第三人民医院肝病研究所，广东深圳518112
    3
    南方科技大学医学院附属第二医院，深圳518112
    4
    传染病诊断与治疗国家重点实验室，传染病诊断与治疗协同创新中心，医学院第一附属医院，浙江大学医学院国家传染病临床研究中心，杭州庆春路79号，310003，浙江，中国。 [email protected]。

    PMID：33845868 PMCID：PMC8040234 DOI：10.1186 / s13099-021-00421-9

免费PMC文章
抽象的

干扰素-α（IFN-α）和核苷酸类似物（NAs）是用于治疗慢性乙型肝炎病毒（HBV）感染的一线药物。通常，NAs靶向HBV前基因组RNA的逆转录，但不能消除共价闭合的环状DNA（cccDNA）。尽管用NAs进行有效治疗可以显着降低HBV蛋白和DNA负荷，甚至促进血清学转化，但由于缺少有效的抗cccDNA药物，cccDNA仍保留在肝细胞核中。在目前可用的药物中，只有IFN-α可以潜在地靶向cccDNA。但是，在HBV患者的肝细胞中使用IFN-α消除cccDNA的临床效果并不如预期的那样熟练，也未得到很好的理解。本文中，我们综述了涉及cccDNA修饰的IFN-α的抗HBV机制，这是治疗HBV感染的最有希望的方法。我们希望找到有希望的研究领域的迹象，这些领域需要进一步研究以消除患者HBV cccDNA。

关键词：慢性HBV感染；共价封闭的环状DNA（cccDNA）；脱氨基；乙型肝炎病毒;干扰素-α。

StephenW

https://gutpathogens.biomedcentr ... 099-021-00421-9.pdf