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PMID: 9060688 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Dengue virus replication in human hepatoma cells activates NF-kappaB which in turn induces apoptotic cell death.

Journal of virology ·Vol. 71 ·No. 4 ·1997-04-00 ·Pages 3244-9

Marianneau P, Cardona A, Edelman L, Deubel V, Desprès P

Abstract

The severe outcome of the dengue (DEN) virus infection known as DEN hemorrhagic fever-DEN shock syndrome (DHF-DSS) is, in some cases, accompanied by liver injury. Councilman bodies observed in liver biopsies of DHF-DSS cases may correspond to hepatocytes in apoptosis. We show here that infection of the hepatoma cell line HepG2 with DEN type 1 virus induced cell death typical of apoptosis late in the virus cycle. The transcription factor NF-kappaB was activated concomitantly with viral protein synthesis and thus before the appearance of apoptotic cells. Inhibition of apoptosis was observed when DEN virus-infected cells were treated with NF-kappaB decoys, indicating the involvement of this transcription factor in induction of cell death. Thus, infected hepatocytes appear to be subject to apoptosis in vitro, and this may be a key element in the pathophysiology of hepatic failure associated with DHF-DSS.

MeSH Terms
Animals Apoptosis Cell Line DNA Fragmentation Dengue Virus/physiology Humans Liver/cytology NF-kappa B/metabolism Signal Transduction Tumor Cells, Cultured Virus Replication
Chemicals
NF-kappa B
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Marianneau P
Unité des Arbovirus et Virus des Fièvres Hémorragiques, Institut Pasteur, Paris, France.
Cardona A
Edelman L
Deubel V
Desprès P
References (55)
55 references, click to expand
  1. Bcl-2 down-regulates the activity of transcription factor NF-kappaB induced upon apoptosis.
    J Cell Biol. 1996 Jul;134(1):13-23 PMID: 8698809
  2. Human cytomegalovirus ie1 transactivates the alpha promoter-enhancer via an 18-base-pair repeat element.
    J Virol. 1989 Mar;63(3):1435-40 PMID: 2536844
  3. Transcriptional inhibition of the inducible nitric oxide synthase gene by competitive binding of NF-kappa B/Rel proteins.
    Biochem Biophys Res Commun. 1995 Apr 6;209(1):73-9 PMID: 7537042
  4. Programmed cell death, apoptosis and killer genes.
    Immunol Today. 1993 Dec;14(12):582-90 PMID: 8305131
  5. The human T-cell leukemia virus type I Tax protein induces apoptosis which is blocked by the Bcl-2 protein.
    J Virol. 1994 May;68(5):3374-9 PMID: 8151796
  6. Differential regulation of p53, c-Myc, Bcl-2 and Bax protein expression during apoptosis induced by widely divergent stimuli in human hepatoblastoma cells.
    Oncogene. 1996 Aug 1;13(3):609-16 PMID: 8760302
  7. H2O2 and antioxidants have opposite effects on activation of NF-kappa B and AP-1 in intact cells: AP-1 as secondary antioxidant-responsive factor.
    EMBO J. 1993 May;12(5):2005-15 PMID: 8491191
  8. Activation of NF-kappa B by the Tax protein of HTLV-1.
    Immunobiology. 1995 Jul;193(2-4):128-36 PMID: 8530135
  9. Viruses and apoptosis.
    Curr Opin Genet Dev. 1995 Feb;5(1):105-11 PMID: 7749317
  10. A novel human protease similar to the interleukin-1 beta converting enzyme induces apoptosis in transfected cells.
    EMBO J. 1995 May 1;14(9):1914-22 PMID: 7743998
  11. Hepatitis B virus pX activates NF-kappa B-dependent transcription through a Raf-independent pathway.
    J Virol. 1996 Jan;70(1):641-6 PMID: 8523586
  12. The cytopathic effect of HIV is associated with apoptosis.
    Virology. 1991 Dec;185(2):829-39 PMID: 1683728
  13. Oxidative stress induces apoptosis in embryonic cortical neurons.
    J Neurochem. 1994 Jan;62(1):376-9 PMID: 7903353
  14. Dengue 1 virus binding to human hepatoma HepG2 and simian Vero cell surfaces differs.
    J Gen Virol. 1996 Oct;77 ( Pt 10):2547-54 PMID: 8887489
  15. Bcl-2 functions in an antioxidant pathway to prevent apoptosis.
    Cell. 1993 Oct 22;75(2):241-51 PMID: 7503812
  16. Recovery of virus from the liver of children with fatal dengue: reflections on the pathogenesis of the disease and its possible analogy with that of yellow fever.
    Res Virol. 1989 Jul-Aug;140(4):351-60 PMID: 2772416
  17. Structure, regulation and function of NF-kappa B.
    Annu Rev Cell Biol. 1994;10:405-55 PMID: 7888182
  18. Liver biochemical tests and dengue fever.
    Am J Trop Med Hyg. 1992 Sep;47(3):265-70 PMID: 1355950
  19. N-acetylcysteine inhibits apoptosis and decreases viral particles in HIV-chronically infected U937 cells.
    FEBS Lett. 1993 Jul 19;327(1):75-8 PMID: 7687566
  20. Optical imaging of the spatial distribution of beta-particles emerging from surfaces.
    Proc Natl Acad Sci U S A. 1989 Mar;86(6):1741-5 PMID: 2928300
  21. Antibody, macrophages, dengue virus infection, shock, and hemorrhage: a pathogenetic cascade.
    Rev Infect Dis. 1989 May-Jun;11 Suppl 4:S830-9 PMID: 2665015
  22. Ultrastructural features of fetal erythroid precursors infected with parvovirus B19 in vitro: evidence of cell death by apoptosis.
    J Pathol. 1993 Feb;169(2):213-20 PMID: 8445486
  23. Conversion of lytic to persistent alphavirus infection by the bcl-2 cellular oncogene.
    Nature. 1993 Feb 25;361(6414):739-42 PMID: 8441470
  24. Epstein-Barr virus induces fragmentation of chromosomal DNA during lytic infection.
    J Virol. 1993 Dec;67(12):7654-8 PMID: 8230485
  25. NF-kappa B: ten years after.
    Cell. 1996 Oct 4;87(1):13-20 PMID: 8858144
  26. Cellular distribution of nuclear factor kappa B binding activity in rat liver.
    Biochem J. 1992 Oct 15;287 ( Pt 2):645-9 PMID: 1445224
  27. Involvement of the CD95 (APO-1/Fas) receptor and ligand in liver damage.
    J Exp Med. 1995 Nov 1;182(5):1223-30 PMID: 7595193
  28. Expression of influenza virus hemagglutinin activates transcription factor NF-kappa B.
    J Virol. 1995 Mar;69(3):1480-4 PMID: 7853480
  29. Molecular interactions between HTLV-1 Tax protein and the NF-kappa B/kappa B transcription complex.
    Virology. 1995 Dec 1;214(1):3-11 PMID: 8525633
  30. Reactive oxygen intermediates as apparently widely used messengers in the activation of the NF-kappa B transcription factor and HIV-1.
    EMBO J. 1991 Aug;10(8):2247-58 PMID: 2065663
  31. Priming of immature thymocytes to CD3-mediated apoptosis by infection with murine cytomegalovirus.
    J Virol. 1994 Jul;68(7):4322-8 PMID: 8207807
  32. Alphavirus-induced apoptosis in mouse brains correlates with neurovirulence.
    J Virol. 1996 Mar;70(3):1828-35 PMID: 8627707
  33. Protein kinase C-zeta mediates NF-kappa B activation in human immunodeficiency virus-infected monocytes.
    J Virol. 1996 Jan;70(1):223-31 PMID: 8523529
  34. Apoptosis as a cause of death in measles virus-infected cells.
    J Virol. 1995 Jun;69(6):3955-8 PMID: 7745753
  35. Modulation of the antioxidant defence as a factor in apoptosis.
    Cell Death Differ. 1996 Jan;3(1):63-70 PMID: 17180056
  36. A single chicken anemia virus protein induces apoptosis.
    J Virol. 1994 Jan;68(1):346-51 PMID: 8254747
  37. Human isolates of dengue type 1 virus induce apoptosis in mouse neuroblastoma cells.
    J Virol. 1996 Jun;70(6):4090-6 PMID: 8648748
  38. Demonstration of yellow fever and dengue antigens in formalin-fixed paraffin-embedded human liver by immunohistochemical analysis.
    Am J Trop Med Hyg. 1991 Oct;45(4):408-17 PMID: 1951849
  39. LMP-1 activates NF-kappa B by targeting the inhibitory molecule I kappa B alpha.
    J Virol. 1995 Apr;69(4):2168-74 PMID: 7884865
  40. Correlation of E protein binding with cell susceptibility to dengue 4 virus infection.
    J Gen Virol. 1992 Aug;73 ( Pt 8):2155-9 PMID: 1645154
  41. Bcl-2 protects from lethal hepatic apoptosis induced by an anti-Fas antibody in mice.
    Nat Med. 1996 Jan;2(1):80-6 PMID: 8564847
  42. Apoptosis: molecular regulation of cell death.
    Eur J Biochem. 1996 Feb 15;236(1):1-26 PMID: 8617251
  43. A novel signal transduction pathway from the endoplasmic reticulum to the nucleus is mediated by transcription factor NF-kappa B.
    EMBO J. 1995 Jun 1;14(11):2580-8 PMID: 7781611
  44. Human T-cell lymphotropic virus type 1 Tax1 activation of NF-kappa B: involvement of the protein kinase C pathway.
    J Virol. 1996 Apr;70(4):2525-32 PMID: 8642682
  45. Apoptosis-inducing and apoptosis-preventing functions of poliovirus.
    J Virol. 1995 Feb;69(2):1181-9 PMID: 7529330
  46. NF-kappa B: a lesson in family values.
    Cell. 1995 Feb 24;80(4):529-32 PMID: 7867060
  47. Thiol agents and Bcl-2 identify an alphavirus-induced apoptotic pathway that requires activation of the transcription factor NF-kappa B.
    J Cell Biol. 1995 Dec;131(5):1149-61 PMID: 8522579
  48. Transcription factors DNA-binding activity in rat thymocytes undergoing apoptosis after heat-shock or dexamethasone treatment.
    Biochem Biophys Res Commun. 1993 Dec 15;197(2):709-15 PMID: 8267607
  49. Evaluation of the plasma kinin system in dengue hemorrhagic fever.
    J Lab Clin Med. 1975 Sep;86(3):410-21 PMID: 1151158
  50. The nature of piecemeal necrosis in chronic active hepatitis.
    Lancet. 1979 Oct 20;2(8147):827-8 PMID: 90921
  51. The Ras-Raf pathway is activated in human immunodeficiency virus-infected monocytes and particpates in the activation of NF-kappa B.
    J Virol. 1996 Apr;70(4):2332-8 PMID: 8642660
  52. Extracellular human immunodeficiency virus type 1 Tat protein is associated with an increase in both NF-kappa B binding and protein kinase C activity in primary human astrocytes.
    J Virol. 1996 Mar;70(3):1384-9 PMID: 8627654
  53. Stabilization of the p53 tumor suppressor is induced by adenovirus 5 E1A and accompanies apoptosis.
    Genes Dev. 1993 Apr;7(4):535-45 PMID: 8384579
  54. Intracellular redox changes during apoptosis.
    Cell Death Differ. 1996 Jan;3(1):57-62 PMID: 17180055
  55. Dengue haemorrhagic fever: a pathological study.
    Trans R Soc Trop Med Hyg. 1968;62(5):682-92 PMID: 5707920
Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/JVI.71.4.3244-3249.1997
Published
1997-04-00
Pages
3244-9
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC191457
Subset
IM
External Links
PubMed source DOI: 10.1128/JVI.71.4.3244-3249.1997 PMC Full Text View journal details
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