细胞内白细胞介素-32γ介导细胞因子对乙型肝炎病毒的抗病

StephenW

Nat Commun. 2018 Aug 16;9(1):3284. doi: 10.1038/s41467-018-05782-5.
Intracellular interleukin-32γ mediates antiviral activity of cytokines against hepatitis B virus.
Kim DH1, Park ES1, Lee AR1, Park S1, Park YK1, Ahn SH1, Kang HS1, Won JH1, Ha YN1, Jae B1, Kim DS2, Chung WC3, Song MJ3, Kim KH4, Park SH5, Kim SH6, Kim KH7,8.
Author information

1
    Department of Pharmacology and Center for Cancer Research and Diagnostic Medicine, IBST, School of Medicine, Konkuk University, Seoul 05029, Republic of Korea.
2
    Division of HBP Surgery and Liver Transplantation, Department of Surgery, Korea University College of Medicine, Seoul 02841, Republic of Korea.
3
    Virus-Host Interactions Laboratory, Division of Biotechnology, Department of Biosystems and Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 02841, Republic of Korea.
4
    Department of Surgery, Uijeongbu St. Mary's Hospital, Catholic Central Laboratory of Surgery, College of Medicine, The Catholic University of Korea, Seoul 11765, Republic of Korea.
5
    Department of Anatomy, School of Medicine, Konkuk University, Seoul 05029, Republic of Korea.
6
    Laboratory of Cytokine Immunology, Veterinary School, Konkuk University, Seoul 05029, Republic of Korea.
7
    Department of Pharmacology and Center for Cancer Research and Diagnostic Medicine, IBST, School of Medicine, Konkuk University, Seoul 05029, Republic of Korea. [email protected].
8
    KU Open Innovation Center, Research Institute of Medical Sciences, Konkuk University, Seoul 05029, Republic of Korea. [email protected].

Abstract

Cytokines are involved in early host defense against pathogen infections. In particular, tumor necrosis factor (TNF) and interferon-gamma (IFN-γ) have critical functions in non-cytopathic elimination of hepatitis B virus (HBV) in hepatocytes. However, the molecular mechanisms and mediator molecules are largely unknown. Here we show that interleukin-32 (IL-32) is induced by TNF and IFN-γ in hepatocytes, and inhibits the replication of HBV by acting intracellularly to suppress HBV transcription and replication. The gamma isoform of IL-32 (IL-32γ) inhibits viral enhancer activities by downregulating liver-enriched transcription factors. Our data are validated in both an in vivo HBV mouse model and primary human hepatocytes. This study thus suggests that IL-32γ functions as intracellular effector in hepatocytes for suppressing HBV replication to implicate a possible mechanism of non-cytopathic viral clearance.

PMID:
    30115930
DOI:
    10.1038/s41467-018-05782-5

StephenW

Nat Commun。 2018年8月16日; 9（1）：3284。 doi：10.1038 / s41467-018-05782-5。
细胞内白细胞介素-32γ介导细胞因子对乙型肝炎病毒的抗病毒活性。
Kim DH1，Park ES1，Lee AR1，Park S1，Park YK1，Ahn SH1，Kang HS1，Won JH1，Ha YN1，Jae B1，Kim DS2，Chung WC3，Song MJ3，Kim KH4，Park SH5，Kim SH6，Kim KH7 8。
作者信息

1
    韩国首尔康氧大学医学院IBST药理学和癌症研究与诊断医学中心，首尔05029。
2
    韩国大学医学院外科，HBP手术和肝移植科，韩国首尔02841。
3
    韩国大学生命科学与生物技术学院生物系统与生物技术系生物技术系病毒宿主相互作用实验室，韩国首尔02841。
4
    韩国天主教大学医学院天宫中心实验室，Uijeongbu St. Mary医院外科，韩国首尔11765。
五
    韩国建国大学医学院解剖学系，首尔05029。
6
    韩国Konkuk大学兽医学院细胞因子免疫学实验室，首尔05029。
7
    韩国首尔康氧大学医学院IBST药理学和癌症研究与诊断医学中心，首尔05029。 [email protected]。
8
    KU开放式创新中心，Konkuk大学医学科学研究所，韩国首尔05029。 [email protected]。

抽象

细胞因子参与早期宿主防御病原体感染。特别地，肿瘤坏死因子（TNF）和干扰素-γ（IFN-γ）在肝细胞中非致细胞病变消除乙型肝炎病毒（HBV）中具有关键功能。然而，分子机制和介体分子在很大程度上是未知的。在这里我们显示白细胞介素-32（IL-32）由肝细胞中的TNF和IFN-γ诱导，并通过细胞内作用抑制HBV转录和复制来抑制HBV的复制。 IL-32（IL-32γ）的γ同种型通过下调富含肝脏的转录因子来抑制病毒增强子活性。我们的数据在体内HBV小鼠模型和原代人肝细胞中均得到验证。因此，该研究表明IL-32γ在肝细胞中起细胞内效应物的作用，用于抑制HBV复制，从而暗示非细胞病变病毒清除的可能机制。

结论：
    30115930
DOI：
    10.1038 / s41467-018-05782-5