Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
International Journal of Molecular Medicine
Join Editorial Board Propose a Special Issue
Print ISSN: 1107-3756 Online ISSN: 1791-244X
Journal Cover
April 2012 Volume 29 Issue 4

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
April 2012 Volume 29 Issue 4

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article

Hepatitis B virus X protein inhibits extracellular IFN-α-mediated signal transduction by downregulation of type I IFN receptor

  • Authors:
    • Il-Rae Cho
    • Myungju Oh
    • Sang Seok Koh
    • Waraporn Malilas
    • Ratakorn Srisuttee
    • Byung Hak Jhun
    • Sandra Pellegrini
    • Serge Y. Fuchs
    • Young-Hwa Chung
  • View Affiliations / Copyright

    Affiliations: WCU Department of Cogno-Mechatronics Engineering, Pusan National University, Busan 609-735, Republic of Korea
  • Pages: 581-586
    |
    Published online on: January 3, 2012
       https://doi.org/10.3892/ijmm.2012.879
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

We have previously shown that hepatitis B virus (HBV) protein X (HBX), a regulatory protein of HBV, activates Stat1, leading to type I interferon (IFN) production. Type I IFN secreted from HBX-expressing hepatic cells enforces antiviral signals through its binding to the cognate type I IFN receptor. We therefore investigated how cells handle this detrimental situation. Interestingly, compared to Chang cells stably expressing an empty vector (Chang-Vec), Chang cells stably expressing HBX (Chang-HBX) showed lower levels of IFN-α receptor 1 (IFNAR1) protein, a subunit of type I IFN receptor. The levels of IFNAR1 transcripts detected in Chang-HBX cells were lower than the levels in Chang-Vec cells, indicating that HBX regulates IFNAR1 at the transcriptional level. Moreover, we observed that HBX induced the translocation of IFNAR1 to the cytoplasm. Consistent with these observations, HBX also downregulated Tyk2, which is required for the stable expression of IFNAR1 on the cell surface. Eventually, Chang-HBX cells consistently maintained a lower level of IFNAR1 expression and displayed no proper response to IFN-α, while Chang-Vec cells exhibited a proper response to IFN-α treatment. Taken together, we propose that HBX downregulates IFNAR1, leading to the avoidance of extracellular IFN-α signal transduction.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

View References

1 

B Payelle-BrogardS PellegriniBiochemical monitoring of the early endocytic traffic of the type I interferon receptorJ Interferon Cytokine Res308998201010.1089/jir.2009.004420028207

2 

TC YehS PellegriniThe Janus kinase family of protein tyrosine kinases and their role in signalingCell Mol Life Sci5515231534199910.1007/s00018005039210526570

3 

GR StarkIM KerrBR WilliamsRH SilvermanRD SchreiberHow cells respond to interferonsAnnu Rev Biochem67227264199810.1146/annurev.biochem.67.1.2279759489

4 

JS BonifacinoLM TraubSignals for sorting of transmembrane proteins to endosomes and lysosomesAnnu Rev Biochem72395447200310.1146/annurev.biochem.72.121801.16180012651740

5 

KG KumarH BarriereCJ CarboneJ LiuG SwaminathanP XuY LiDP BakerJ PengGL LukacsSY FuchsSite-specific ubiquitination exposes a linear motif to promote interferon-alpha receptor endocytosisJ Cell Biol179935950200710.1083/jcb.20070603418056411

6 

J LiuA PlotnikovA BanerjeeKG Suresh KumarJ RagimbeauZ MarijanovicDP BakerS PellegriniSY FuchsLigand-independent pathway that controls stability of interferon alpha receptorBiochem Biophys Res Commun367388393200810.1016/j.bbrc.2007.12.13718166147

7 

J RagimbeauE DondiA AlcoverP EidG UzeS PellegriniThe tyrosine kinase Tyk2 controls IFNAR1 cell surface expressionEMBO J22537547200310.1093/emboj/cdg03812554654

8 

KG KumarB VargheseA BanerjeeDP BakerSN ConstantinescuS PellegriniSY FuchsBasal ubiquitin-independent internalization of interferon alpha receptor is prevented by Tyk2-mediated masking of a linear endocytic motifJ Biol Chem2831856618572200810.1074/jbc.M800991200

9 

DH NguyenL LudgateJ HuHepatitis B virus-cell interactions and pathogenesisJ Cell Physiol216289294200810.1002/jcp.2141618302164

10 

G WarisKW HuhA SiddiquiMitochondrially associated hepatitis B virus X protein constitutively activates transcription factors STAT-3 and NF-kappa B via oxidative stressMol Cell Biol2177217730200110.1128/MCB.21.22.7721-7730.2001

11 

AS KekuleU LauerL WeissB LuberPH HofschneiderHepatitis B virus transactivator HBx uses a tumour promoter signalling pathwayNature361742745199310.1038/361742a08441471

12 

YH LeeY YunHBx protein of hepatitis B virus activates Jak1-STAT signalingJ Biol Chem2732551025515199810.1074/jbc.273.39.255109738022

13 

YI LeeS Kang-ParkSI DoYI LeeThe hepatitis B virus-X protein activates a phosphatidylinositol 3-kinase-dependent survival signaling cascadeJ Biol Chem2761696916977200110.1074/jbc.M01126320011278872

14 

P ChirilloM FalcoPL PuriM ArtiniC BalsanoM LevreroG NatoliHepatitis B virus pX activates NF-kappa B-dependent transcription through a Raf-independent pathwayJ Virol7064164619968523586

15 

H KimYH LeeJ WonY YunThrough induction of juxtaposition and tyrosine kinase activity of Jak1, X-gene product of hepatitis B virus stimulates Ras and the transcriptional activation through AP-1, NF-kappaB, and SRE enhancersBiochem Biophys Res Commun286886894200110.1006/bbrc.2001.549611527382

16 

J ChenA SiddiquiHepatitis B virus X protein stimulates the mitochondrial translocation of Raf-1 via oxidative stressJ Virol8167576760200710.1128/JVI.00172-0717428866

17 

R SrisutteeSS KohEH ParkIR ChoHJ MinBH JhunDY YuS ParkY Park doMO LeeUpregulation of Foxo4 mediated by hepatitis B virus X protein confers resistance to oxidative stress-induced cell deathInt J Mol Med28255260201121567078

18 

EH ParkSS KohR SrisutteeIR ChoHJ MinBH JhunYS LeeKL JangCH KimRN JohnstonYH ChungExpression of HBX, an oncoprotein of hepatitis B virus, blocks reoviral oncolysis of hepatocellular carcinoma cellsCancer Gene Ther16453461200910.1038/cgt.2008.9519096445

19 

IR ChoS JeongBH JhunWG AnB LeeYT KwakSH LeeJU JungYH ChungActivation of non-canonical NF-kappaB pathway mediated by STP-A11, an oncoprotein of Herpesvirus saimiriVirology3593745200710.1016/j.virol.2006.09.00117028057

20 

H IdeT NakagawaY TeradoY KamiyamaS MutoS HorieTyk2 expression and its signaling enhances the invasiveness of prostate cancer cellsBiochem Biophys Res Commun369292296200810.1016/j.bbrc.2007.08.16017920038

21 

PM Mulrooney-CousinsTI MichalakPersistent occult hepatitis B virus infection: experimental findings and clinical implicationsWorld J Gastroenterol1356825686200710.3748/wjg.v13.i43.568217963292

22 

SI GrivennikovFR GretenM KarinImmunity, inflammation, and cancerCell140883899201010.1016/j.cell.2010.01.025

23 

MG BorrelloD Degl’InnocentiMA PierottiInflammation and cancer: the oncogene-driven connectionCancer Lett267262270200810.1016/j.canlet.2008.03.06018502035

24 

S LiS LabrecqueMC GauzziAR CuddihyAH WongS PellegriniGJ MatlashewskiAE KoromilasThe human papilloma virus (HPV)-18 E6 oncoprotein physically associates with Tyk2 and impairs Jak-STAT activation by interferon-alphaOncogene1857275737199910.1038/sj.onc.120296010523853

25 

RJ LinCL LiaoE LinYL LinBlocking of the alpha interferon-induced Jak-Stat signaling pathway by Japanese encephalitis virus infectionJ Virol7892859294200410.1128/JVI.78.17.9285-9294.200415308723

26 

JT GuoJ HayashiC SeegerWest Nile virus inhibits the signal transduction pathway of alpha interferonJ Virol7913431350200510.1128/JVI.79.3.1343-1350.200515650160

27 

D GarcinJB MarqL StrahleP le MercierD KolakofskyAll four Sendai Virus C proteins bind Stat1, but only the larger forms also induce its mono-ubiquitination and degradationVirology295256265200210.1006/viro.2001.134212033784

28 

B GotohT KomatsuK TakeuchiJ YokooParamyxovirus strategies for evading the interferon responseRev Med Virol12337357200210.1002/rmv.35712410527

29 

P BarnardNA McMillanThe human papillomavirus E7 oncoprotein abrogates signaling mediated by interferon-alphaVirology259305313199910.1006/viro.1999.977110388655

30 

DC LookWT RoswitAG FrickY Gris-AlevyDM DickhausMJ WalterMJ HoltzmanDirect suppression of Stat1 function during adenoviral infectionImmunity9871880199810.1016/S1074-7613(00)80652-49881977

31 

V ChristenF DuongC BernsmeierD SunM NassalMH HeimInhibition of alpha interferon signaling by hepatitis B virusJ Virol81159165200710.1128/JVI.01292-0617065208

32 

SA BissonAL PageD GanemA Kaposi’s sarcoma-associated herpesvirus protein that forms inhibitory complexes with type I interferon receptor subunits, Jak and STAT proteins, and blocks interferon-mediated signal transductionJ Virol83505650662009

33 

C WuQ GuanY WangZJ ZhaoGW ZhouSHP-1 suppresses cancer cell growth by promoting degradation of JAK kinasesJ Cell Biochem9010261037200310.1002/jcb.1072714624462

34 

J ChengD ZhangC ZhouWA MarascoDownregulation of SHP1 and up-regulation of negative regulators of JAK/STAT signaling in HTLV-1 transformed cell lines and freshly transformed human peripheral blood CD4+ T-cellsLeuk Res287182200410.1016/S0145-2126(03)00158-914630083

35 

C WuM SunL LiuGW ZhouThe function of the protein tyrosine phosphatase SHP-1 in cancerGene306112200310.1016/S0378-1119(03)00400-112657462

36 

TW ChungYC LeeJH KoCH KimHepatitis B Virus X protein modulates the expression of PTEN by inhibiting the function of p53, a transcriptional activator in liver cellsCancer Res6334533458200312839924

37 

K AbdelmohsenR Pullmann JrA LalHH KimS GalbanX YangJD BlethrowM WalkerJ ShubertDA GillespiePhosphorylation of HuR by Chk2 regulates SIRT1 expressionMol Cell25543557200710.1016/j.molcel.2007.01.01117317627

38 

JK JungP AroraJS PaganoKL JangExpression of DNA methyltransferase 1 is activated by hepatitis B virus X protein via a regulatory circuit involving the p16INK4a-cyclin D1-CDK 4/6-pRb-E2F1 pathwayCancer Res6757715778200710.1158/0008-5472.CAN-07-052917575144

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Cho I, Oh M, Koh SS, Malilas W, Srisuttee R, Jhun BH, Pellegrini S, Fuchs SY and Chung Y: Hepatitis B virus X protein inhibits extracellular IFN-α-mediated signal transduction by downregulation of type I IFN receptor. Int J Mol Med 29: 581-586, 2012.
APA
Cho, I., Oh, M., Koh, S.S., Malilas, W., Srisuttee, R., Jhun, B.H. ... Chung, Y. (2012). Hepatitis B virus X protein inhibits extracellular IFN-α-mediated signal transduction by downregulation of type I IFN receptor. International Journal of Molecular Medicine, 29, 581-586. https://doi.org/10.3892/ijmm.2012.879
MLA
Cho, I., Oh, M., Koh, S. S., Malilas, W., Srisuttee, R., Jhun, B. H., Pellegrini, S., Fuchs, S. Y., Chung, Y."Hepatitis B virus X protein inhibits extracellular IFN-α-mediated signal transduction by downregulation of type I IFN receptor". International Journal of Molecular Medicine 29.4 (2012): 581-586.
Chicago
Cho, I., Oh, M., Koh, S. S., Malilas, W., Srisuttee, R., Jhun, B. H., Pellegrini, S., Fuchs, S. Y., Chung, Y."Hepatitis B virus X protein inhibits extracellular IFN-α-mediated signal transduction by downregulation of type I IFN receptor". International Journal of Molecular Medicine 29, no. 4 (2012): 581-586. https://doi.org/10.3892/ijmm.2012.879
Copy and paste a formatted citation
x
Spandidos Publications style
Cho I, Oh M, Koh SS, Malilas W, Srisuttee R, Jhun BH, Pellegrini S, Fuchs SY and Chung Y: Hepatitis B virus X protein inhibits extracellular IFN-α-mediated signal transduction by downregulation of type I IFN receptor. Int J Mol Med 29: 581-586, 2012.
APA
Cho, I., Oh, M., Koh, S.S., Malilas, W., Srisuttee, R., Jhun, B.H. ... Chung, Y. (2012). Hepatitis B virus X protein inhibits extracellular IFN-α-mediated signal transduction by downregulation of type I IFN receptor. International Journal of Molecular Medicine, 29, 581-586. https://doi.org/10.3892/ijmm.2012.879
MLA
Cho, I., Oh, M., Koh, S. S., Malilas, W., Srisuttee, R., Jhun, B. H., Pellegrini, S., Fuchs, S. Y., Chung, Y."Hepatitis B virus X protein inhibits extracellular IFN-α-mediated signal transduction by downregulation of type I IFN receptor". International Journal of Molecular Medicine 29.4 (2012): 581-586.
Chicago
Cho, I., Oh, M., Koh, S. S., Malilas, W., Srisuttee, R., Jhun, B. H., Pellegrini, S., Fuchs, S. Y., Chung, Y."Hepatitis B virus X protein inhibits extracellular IFN-α-mediated signal transduction by downregulation of type I IFN receptor". International Journal of Molecular Medicine 29, no. 4 (2012): 581-586. https://doi.org/10.3892/ijmm.2012.879
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team