干扰素-λ3对细胞培养中乙型肝炎病毒感染的抗病毒作用。

StephenW

Hepatol Res. 2019 Nov 22. doi: 10.1111/hepr.13449. [Epub ahead of print]
Anti-Viral Effects of Interferon-λ3 on Hepatitis B Virus Infection in Cell Culture.
Yamada N1, Murayama A1, Shiina M1,2, Aly HH1, Iwamoto M1, Tsukuda S1,3, Watashi K1, Tanaka T4, Moriishi K4, Nishitsuji H5, Sugiyama M6, Mizokami M6, Shimotohno K5, Muramatsu M1, Murata K7, Kato T1.
Author information

1
    Department of Virology II, National Institute of Infectious Diseases, Tokyo.
2
    Department of Gastroenterology and Hepatology, Shin-Yurigaoka General Hospital, Kawasaki.
3
    Liver Cancer Prevention Research Unit, Center for Integrative Medical Sciences, RIKEN, Wako.
4
    Department of Microbiology, Graduate School of Medicine, University of Yamanashi, Yamanashi.
5
    Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Ichikawa.
6
    Genome Medical Sciences Project, National Center for Global Health and Medicine, Ichikawa.
7
    Department of Gastroenterology, International University of Health and Welfare, Nasushiobara, Tochigi, Japan.

Abstract
AIM:

Interferon (IFN)-λ3 is known to have anti-viral effects against various pathogens. Recently, it has been reported that the production of IFN-λ3 in colon cells following the administration of nucleotide analogues is expected to reduce hepatitis B surface antigen (HBsAg) in chronic hepatitis B patients. Here, we aimed to prove the anti-viral effects of IFN-λ3 on hepatitis B virus (HBV) by using an in vitro HBV production and infection system.
METHODS:

We used HepG2.2.15-derived HBV as an inoculum and the replication-competent molecular clone of HBV as a replication model.
RESULTS:

By administering IFN-λ3 to HepG2 cells transfected with the HBV molecular clone, the production of HBsAg and hepatitis B core-related antigen was reduced dose-dependently. IFN-λ3 treatment also reduced the number of HBV-positive cells and the synthesis of covalently closed circular DNA after infection of HepG2.2.15-derived HBV to sodium taurocholate cotransporting polypeptide-transduced HepG2 cells. The inhibitory effect on HBV infection by IFN-λ3 was confirmed by using a recombinant HBV reporter virus system. To elucidate the underlying mechanisms of the anti-HBV effect of IFN-λ3, we assessed the transcription of HBV RNA and the production of core-associated HBV DNA in HBV molecular clone-transfected HepG2 cells and found that both parameters were reduced by IFN-λ3.
CONCLUSIONS:

We observed that the administration of IFN-λ3 inhibits HBV infection and the production of HBV proteins at the HBV RNA transcription level. This finding provides novel insight into the treatment of chronic hepatitis B patients with the administration or induction of IFN-λ3.

This article is protected by copyright. All rights reserved.
KEYWORDS:

HBV; HBcrAg; HBsAg; IFN; nucleotide analogue

PMID:
    31756766
DOI:
    10.1111/hepr.13449

StephenW

肝素水库。 2019年11月22日.doi：10.1111 / hepr.13449。 [Epub提前发布]
干扰素-λ3对细胞培养中乙型肝炎病毒感染的抗病毒作用。
山田N1，村山A1，椎名M1,2，Aly HH1，岩本M1，筑田S1,3，渡司K1，田中T4，森石K4，西筋H5，杉山M6，Mizokami M6，Shimotohno K5，村松M1，村田K7，加藤T1。
作者信息

1个
    东京国立传染病研究所病毒学系II。
2
    川崎市新尤里高冈综合医院消化内科和肝病科。
3
    和光市理研综合医学中心肝癌预防研究室。
4
    山梨大学医学研究生院微生物学系，山梨县。
5
    市川国立全球健康与医学中心肝炎和免疫学研究中心。
6
    市川国立全球健康与医学中心基因组医学项目。
7
    国际健康与福利大学肠胃病学系，日本University木市那须盐原市。

抽象
目标：

已知干扰素（IFN）-λ3对多种病原体具有抗病毒作用。最近，据报道，核苷酸类似物给药后结肠细胞中IFN-λ3的产生有望减少慢性乙型肝炎患者的乙型肝炎表面抗原（HBsAg）。在这里，我们旨在通过使用体外HBV产生和感染系统来证明IFN-λ3对乙型肝炎病毒（HBV）的抗病毒作用。
方法：

我们使用HepG2.2.15衍生的HBV作为接种物，并使用具有复制能力的HBV分子克隆作为复制模型。
结果：

通过对转染了HBV分子克隆的HepG2细胞施用IFN-λ3，可降低HBsAg和乙型肝炎核心相关抗原的产生。在源自HepG2.2.15的HBV感染牛磺胆酸钠共转运多肽转导的HepG2细胞后，IFN-λ3处理还减少了HBV阳性细胞的数量和共价闭合环状DNA的合成。通过使用重组HBV报告病毒系统证实了对IFN-λ3的HBV感染的抑制作用。为了阐明IFN-λ3的抗HBV效应的潜在机制，我们评估了HBV分子克隆转染的HepG2细胞中HBV RNA的转录和核心相关HBV DNA的产生，发现IFN-λ降低了这两个参数λ3。
结论：

我们观察到，IFN-λ3的施用在HBV RNA转录水平抑制了HBV感染和HBV蛋白的产生。该发现为通过给予或诱导IFN-λ3治疗慢性乙型肝炎患者提供了新颖的见解。

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关键字：

乙肝病毒HBcrAg;乙肝表面抗原干扰素;核苷酸类似物

PMID：
    31756766
DOI：
    10.1111 / hepr.13449