Lack ofin vivo blockade of Fas- and TNFR1-mediated hepatocyte apoptosis by the hepatitis C virus

Autor: Laurent Spahr, Laura Rubbia-Brandt, Rafael Quadri, Karim Abid, Patrizia Gindre, Sophia Taylor, Francesco Negro
Rok vydání: 2002
Předmět:
Genotype
Hepatitis C virus
Apoptosis
Hepacivirus
CD8-Positive T-Lymphocytes
Biology
Virus Replication
medicine.disease_cause
Receptors
Tumor Necrosis Factor
Fas ligand
Pathology and Forensic Medicine
Liver disease
Antigens
CD
In Situ Nick-End Labeling
medicine
Humans
fas Receptor
virus diseases
Hepatitis C
Hepatitis C
Chronic
Fas receptor
medicine.disease
medicine.anatomical_structure
Liver
Receptors
Tumor Necrosis Factor
Type I
Antigens
CD/metabolism
CD8-Positive T-Lymphocytes/pathology
Hepacivirus/genetics
Hepacivirus/isolation & purification
Hepacivirus/physiology
Hepatitis C
Chronic/immunology
Hepatitis C
Chronic/pathology
Hepatocytes/metabolism
Hepatocytes/pathology
Liver/immunology
Liver/virology
RNA
Viral/blood
Receptors
Tumor Necrosis Factor/metabolism
fas Receptor/metabolism
Hepatocyte
Immunology
Hepatocytes
Cancer research
RNA
Viral
Tumor necrosis factor alpha
Zdroj: The Journal of pathology, vol. 197, no. 5, pp. 617-623
ISSN: 1096-9896
0022-3417
DOI: 10.1002/path.1148
Popis: In vitro data have shown that the hepatitis C virus (HCV) core protein binds to protein members of the tumour necrosis factor receptor (TNFR) superfamily. Since this interaction could be relevant to HCV persistence and oncogenesis, this study assessed whether HCV may interfere with the apoptotic cascade in vivo. Apoptosis (by TUNEL) and Fas and TNFR1 expression (by immunohistochemistry) were scored in the liver of 60 chronic hepatitis C patients. Results were compared with the liver disease grading and staging scores and the HCV replication level in serum and liver. Apoptotic hepatocytes were stained in 29 cases. Fas was expressed in 35 cases and TNFR1 in 21, 15 patients (25%) being negative for both receptors. Overall, the numbers of TUNEL-, Fas- and TNFR-positive hepatocytes did not correlate with the extent of intrahepatic CD8+ T-lymphocyte infiltration, the grading and staging of liver disease, or the serum or liver HCV RNA levels. Furthermore, when patients expressing either Fas or TNFR1 were stratified according to serum HCV RNA levels, cases with detectable hepatocyte apoptosis had higher HCV viraemias. In conclusion, an HCV-mediated, in vivo blockade of hepatocyte apoptosis via the Fas- or TNFR1-dependent pathways seems unlikely.
Databáze: OpenAIRE
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