Effect of interferons on expression of adenosine deaminase acting on RNA 1 and hepatitis B virus replication in human hepatocellular carcinoma cells <italic style="font-style: italic">in vitro</italic>

您当前的位置：

首页 >

文章列表页 >

Effect of interferons on expression of adenosine deaminase acting on RNA 1 and hepatitis B virus replication in human hepatocellular carcinoma cells in vitro

Basic Medicine | 更新时间：2026-01-09

- Effect of interferons on expression of adenosine deaminase acting on RNA 1 and hepatitis B virus replication in human hepatocellular carcinoma cells in vitro
- Journal of Third Military Medical University Vol. 41, Issue 14, Pages: 1336-1342(2019)
- 作者机构：
  
  1.400016 重庆，重庆医科大学:感染性疾病分子生物学教育部重点实验室
  2.400016 重庆，重庆医科大学:基础医学院病原生物学教研室，分子医学与肿瘤研究中心
- 作者简介：
- 基金信息：
  
  the Special Project of Basic Science and Frontier Technology Research of Chongqing(CSTC2015jcyjA10006);the National Natural Science Foundation for Young Scholars of China(81501751);the Chongqing Municipal Postdoctoral Science Foundation(Xm2014006)
- DOI：10.16016/j.1000-5404.201901149
  CLC： R735.7; R966; R977.6
- Received：18 January 2019，
  
  Revised：2019-03-10，
  
  Published：30 July 2019
- 稿件说明：
移动端阅览
Yimin LI, Lin YUAN, Shengyong YANG, et al. Effect of interferons on expression of adenosine deaminase acting on RNA 1 and hepatitis B virus replication in human hepatocellular carcinoma cells in vitro[J]. Journal of Third Military Medical University, 2019, 41(14): 1336-1342.
DOI：

Yimin LI, Lin YUAN, Shengyong YANG, et al. Effect of interferons on expression of adenosine deaminase acting on RNA 1 and hepatitis B virus replication in human hepatocellular carcinoma cells in vitro[J]. Journal of Third Military Medical University, 2019, 41(14): 1336-1342. DOI： 10.16016/j.1000-5404.201901149.

摘要

目的

2

探讨Ⅰ型干扰素(IFN-α、IFN-β)和Ⅱ型干扰素(IFN-γ)在肝癌细胞中诱导ADAR1(P110和P150)的表达模式及对HBV复制的作用。

方法

2

不同浓度IFN-α(0、200、500、1 000、2 000 U/mL)、IFN-β(0、200、1 000 U/mL)和IFN-γ(0、200、1 000 U/mL)分别处理肝癌细胞(Huh7和HepG2)，Western blot和RT-qPCR检测肝癌细胞中IFN作用后ADAR1的表达变化；Huh7细胞瞬时转染HBV复制型质粒，IFN-α作用后，Southern blot分析HBV DNA复制中间体水平。

结果

2

Ⅰ型IFN(IFN-α、IFN-β)作用Huh7和HepG2细胞后，ADAR1 P110蛋白水平增加(

P

＜0.05)，同时ADAR1 P150表达水平明显增高(

P

＜0.01)，且ADAR1 P150的表达呈现IFN浓度依赖性；Ⅱ型IFN(IFN-γ)作用Huh7和HepG2细胞后，ADAR1 P110和P150蛋白表达水平没有发生明显变化。IFN-α明显抑制Huh7细胞中HBV复制(

P

＜0.05)，与浓度梯度呈负相关。

结论

2

Ⅰ型IFN可诱导肝癌细胞中ADAR1 P150表达，IFN-α抑制Huh7细胞中HBV复制，其作用可能与ADAR1相关。

Abstract

Objective

2

To investigate the effect of type Ⅰ interferons (IFN-α and IFN-β) and type Ⅱ interferon (IFN-γ) on the expression of adenosine deaminase acting on RNA 1 (ADAR1

P110 and P150) and hepatitis B virus (HBV) replication in hepatocellular carcinoma (HCC) cells.

Methods

2

Western blotting and qRT-PCR were used to detect the expression of ADAR1 in human HCC cell lines HepG2 and Huh7 following treatment with different concentrations of IFN-α

IFN-β or IFN-γ. Southern blotting was employed to detect the changes in HBV DNA level in response to IFN-α treatment in Huh7 and HepG2 cells transfected with HBV replication plasmids.

Results

2

In Huh7 and HepG2 cells

treatments with IFN-α and IFN-β significantly increased the protein expression of ADAR1 P150 in a time- and dose-dependent manner (

P

<

0.01) and also obviously augmented the protein level of ADAR1 P110; IFN-γ did not significantly affected the expression of eithe

r ADAR1 P110 or ADAR1 P150. IFN-α treatment dose-dependently inhibited HBV DNA replication in Huh7 cells (

P

<

0.05).

Conclusion

2

Type Ⅰ interferons time- and dose-dependently increase the expression of ADAR1 in Huh7 and HepG2 cells

suggesting a possible role of ADAR1 in mediating the anti-HBV effect of IFN-α.

关键词

Keywords

references

SCHNEIDER W M, CHEVILLOTTE M D, RICE C M. Interferon-stimulated genes: a complex web of host defenses [J]. Annu Rev Immunol, 2014, 32: 513-545. DOI: 10.1146/annurev-immunol-032713-120231.

TRÉPO C, CHAN H L, LOK A. Hepatitis B virus infection[J]. Lancet, 2014, 384(9959): 2053-2063. DOI: 10.1016/s0140-6736(14)60220-8.

SAMUEL C E. Adenosine deaminases acting on RNA (ADARs) are both antiviral and proviral[J]. Virology, 2011, 411(2): 180-193. DOI: 10.1016/j.virol.2010.12.004.

CHAN T H, LIN C H, QI L, et al . A disrupted RNA editing balance mediated by ADARs (Adenosine Deaminases that act on RNA) in human hepatocellular carcinoma[J ] . Gut, 2014, 63(5): 832-843. DOI:10.1136/gutjnl-2012-304037.

LI Z, OKONSKI K M, SAMUEL C E. Adenosine deaminase acting on RNA 1 (ADAR1) suppresses the induction of interferon by measles virus[J]. J Virol, 2012, 86(7): 3787-3794. DOI:10.1128/JVI.06307-11.

LI Z, WOLFF K C, SAMUEL C E. RNA adenosine deaminase ADAR1 deficiency leads to increased activationof protein kinase PKR and reduced vesicular stomatitis virus growth following interferon treatment[J]. Virology, 2010, 396(2): 316-322. DOI:10.1016/j.virol.2009.10.026.

CROAGH C M, DESMOND P V, BELL S J. Genotypes and viral variants in chronic hepatitis B: A review of epidemiology and clinical relevance[J]. World J Hepatol, 2015, 7(3): 289-303. DOI: 10.4254/wjh.v7.i3.289.

SATO S, LI K, KAMEYAMA T, et al . The RNA sensor RIG-I dually functions as an innate sensor and direct antiviral factor for hepatitis B virus[J ] . Immunity, 2015, 42(1): 123-132. DOI: 10.1016/j.immuni.2014.12.016.

LV M, ZHANG B, SHI Y, et al . Identification of BST-2/tetherin-induced hepatitis B virus restriction and hepatocyte-specific BST-2 inactivation[J ] . Sci Rep, 2015, 5: 11736. DOI: 10.1038/srep11736.

YAN R, ZHAO X, CAI D, et al . The interferon-inducible protein tetherin inhibits hepatitis B virus virion secretion[J ] . J Virol, 2015, 89(18): 9200-9212. DOI: 10.1128/JVI.00933-15.

LEONG C R, FUNAMI K, OSHIUMI H, et al . Interferon-stimulated gene of 20 kDa protein (ISG20) degrades RNA of hepatitis B virus to impede the replication of HBV in vitro and in vivo [J ] . Oncotarget, 2016, 7(42): 68179-68193. DOI: 10.18632/oncotarget.11907..

LIU Y, NIE H, MAO R, et al . Interferon-inducible ribonuclease ISG20 inhibits hepatitis B virus replication through directly binding to the epsilon stem-loop structure of viral RNA[J ] . PLoS Pathog, 2017, 13(4): e1006296. DOI:10.1371/journal.ppat.1006296.

TAN G, XIAO Q, SONG H, et al . Type I IFN augments IL-27-dependent TRIM25 expression to inhibit HBV replication[J ] . Cell Mol Immunol, 2018, 15(3): 272-281. DOI:10.1038/cmi.2016.67.

CHEN Y, HU J, CAI X, et al . APOBEC3B edits HBV DNA and inhibits HBV replication during reverse transcription[J ] . Antiviral Res, 2018, 149: 16-25. DOI: 10.1016/j.antiviral.2017.11.006.

BONVIN M, ACHERMANN F, GREEVE I, et al . Interferon-inducible expression of APOBEC3 editing enzymes in human hepatocytes and inhibition of hepatitis B virus replication[J ] . Hepatology, 2006, 43(6): 1364-1374. DOI: 10.1002/hep.21187.

HU J, QIAO M, CHEN Y, et al . Cyclin E2-CDK2 mediate SAMHD1 phosphorylation to abrogate its restriction of HBV replication in hepatoma cells[J ] . FEBS Lett, 2018, 592(11): 1893-1904. DOI: 10.1002/1873- 3468.13105.

JEONG G U, PARK I H, AHN K, et al . Inhibition of hepatitis B virus replication by a dNTPase-dependent function of the host restriction factor SAMHD1[J ] . Virology, 2016, 495: 71-78. DOI: 10.1016/j.virol.2016.05.001.

LI L, LEI Q S, ZHANG S J, et al . suppression of USP18 potentiates the anti-HBV activity of interferon alpha in HepG2.2.15 cells via JAK/STAT signaling[J ] . PLoS ONE, 2016, 11(5): e0156496. DOI: 10.1371/journal.pone.0156496..

LI Y, LI S, DUAN X. et al . Interferon-stimulated gene 15 conjugation stimulates hepatitis B virus production independent of type Ⅰ interferon signaling pathway in vitro [J ] . Mediators Inflamm, 2016, 2016: 7417648. DOI: 10.1155/2016/7417648.

KOEBERLEIN B, ZUR HAUSEN A, BEKTAS N, et al . Hepatitis B virus overexpresses suppressor of cytokine signaling-3 (SOCS3) thereby contributing to severity of inflammation in the liver[J ] . Virus Res, 2010, 148(1/2): 51-59. DOI: 10.1016/j.virusres.2009.12.003.

郜衍周, 范红霞, 邱立鹏, 等. IFN-α对gp96的上调降低其抗HBV的效率[J].微生物学报, 2013, 53(8): 867-874.

HAO Y Z, FAN H X, QIU L P. et al IFN-α-induced gp96 upregulation negatively affects the anti-HBV efficiency of IFN-α [J ] . Acta Microbiol Sinica, 2013, 53(8): 867-874.

XIAO C, QIN B, CHEN L, et al . Preactivation of the interferon signalling in liver is correlated with nonresponse to interferon alpha therapy in patients chronically infected with hepatitis B virus[J ] . J Viral Hepat, 2012, 19(2): e1-e10. DOI: 10.1111/j.1365-2893.2011.01471.x.

HAN M, LI Y, WU W, et al . Altered expression of interferon-stimulated genes is strongly associated with therapeutic outcomes in hepatitis B virus infection[J ] . Antiviral Res, 2017, 147: 75-85. DOI: 10.1016/j.antiviral.2017.10.003.

WU X, SHI W, WU J, et al . A functional polymorphism in ADAR 1 gene affects HBsAg seroclearance both spontaneously and interferon induced[J ] . Liver Int, 2014, 34(10): 1560-1565. DOI: 10.1111/liv.12444.

李京源, 李涛, 朱席琳, 等. ADAR1通过RNA编辑上调ZNF655表达并促进人肝癌细胞系HepG2中HBV复制[J].基础医学与临床, 2018, 38(3): 312-316. DOI: 10.16352/j.issn.1001-6325.2018.03.006.

LI J Y, LI T, ZHU X L, et al . ADAR1 up-regulates ZNF655 expression via RNA editing and e nhances HBV replication in HepG2 cell line[J ] . Basic Clin Med, 2018, 38(3): 312-316. DOI: 10.16352/j.issn.1001-6325.2018.03.006..

LI L, QIAN G, ZUO Y, et al . Ubiquitin-dependent turnover of adar1 is required for efficient antiviral activity of type Ⅰ interferon[J ] . J Biol Chem, 2016, 291(48): 24974-24985. DOI: 10.1074/jbc.M116.737098.

0

Views

0

下载量

0

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

Related Articles

SRSF1 inhibits HBV replication by enhancing the stability of P53 in cell models

AKT1-mediated autophagy of hepatocellular carcinoma cells enhances cell sensitivity to ¹²⁵I seed irradiation

Dynamic analysis of serum markers of HBV in 302 infants of pregnant women with HBV infection

Related Author

LIU Jiajun

LONG Shaoyuan

HU Jieli

CUI Jing

WANG Chenyu

WU Zhizhou

LIU li

XIAO Yunhua

Related Institution

Key Laboratory of Molecular Biology for Infectious Diseases of Ministry of Education， Chongqing Medical University

First Affiliated Hospital， Air Force Medical University

Department of Nuclear Medicine， First Affiliated Hospital， Army Medical University （Third Military Medical University）

Institute of Infectious Diseases, Chongqing Key Laboratory of Infectious Diseases Research, First Affiliated Hospital, Army Medical University (Third Military Medical University)

Faculty of Pharmaceutical Sciences, Chongqing Cancer Institute & Hospital & Cancer Center

⁰