Hepatitis C virus core, NS3, NS5A, NS5B proteins induce apoptosis in mature dendritic cells.
Although reasons for hepatitis C virus (HCV) persistence are still unknown, specific cellular immune responses appear to influence the pathogenesis and outcome of the infection. Apoptosis of cells infected by viruses may appear suicidal to the viruses that induce programmed cell death of its host. However, apoptosis has been suggested to be a response to virus infection as a mean of facilitating virus dissemination. Annexin V-propidium iodide staining and DNA fragmentation, were used to show that expression of the core, NS3, NS5A, or NS5B protein induces apoptosis in mature dendritic cells. In addition, immunoblotting was used to demonstrate that expression level of p21waf1/cip1 protein decreased in cells expressing one of these HCV proteins. No expression of p53 could be detected and expression of Akt was independent of HCV proteins expression. These results suggest that the effect of these HCV proteins on HCV associated pathogenesis may be linked (at least partially) to its ability to modulate apoptosis pathways in mature dendritic cells.
Siavoshian
Samila
S
INSERM U544, Strasbourg, France.
Abraham
Jean Daniel
JD
Thumann
Christine
C
Kieny
Marie Paule
MP
Schuster
Catherine
C
D017209:Apoptosis; D018797:Cell Cycle Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D050759:Cyclin-Dependent Kinase Inhibitor p21; D053938:DNA Fragmentation; D003713:Dendritic Cells / Q000821:virology*; D016174:Hepacivirus / Q000472:pathogenicity*; D006801:Humans; D015151:Immunoblotting; D010641:Phenotype; D011419:Propidium / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D014161:Transduction, Genetic; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D017361:Viral Nonstructural Proteins / Q000502:physiology*; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; D012324:RNA-Dependent RNA Polymerase
D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D011419:Propidium; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D016159:Tumor Suppressor Protein p53; D017361:Viral Nonstructural Proteins; C493956:CDKN1A protein, human; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; C494918:AKT1 protein, human; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase