HCV Infection and Interferon-Based Treatment Induce p53 Gene Transcription in Chronic Hepatitis C Patients.
It is suggested that the tumor suppressor p53 gene, classified as an interferon-stimulated gene, is implicated in the interferon (IFN)-mediated innate immunity against viruses. This study aimed to examine the transcriptional response of the p53 gene to hepatitis C virus (HCV) infection and IFN-based therapy in chronic hepatitis C (CHC) patients. The study included 65 CHC patients (HCV genotype 1), treated with pegylated IFN-α and ribavirin, and 51 healthy individuals. p53 gene expression was quantified by real-time polymerase chain reaction in peripheral blood mononuclear cells (PBMCs). Analyses were performed before and at weeks 4 and 12 of treatment. p53 gene expression was significantly upregulated in CHC patients compared with healthy controls and at week 4 of therapy. No significant differences in p53 mRNA expression between rapid virologic responders, complete early virologic responders, and nonresponders were observed. No significant correlation was found between p53 gene expression and viral load. The results obtained indicate that HCV infection and IFN-based treatment induces p53 gene transcription in PBMCs. The p53 gene may therefore play a role in HCV infection but is not directly involved in treatment-induced HCV elimination. Moreover, variations in p53 gene expression do not determine on-treatment response in patients with chronic HCV genotype 1 infection.
1 Department of Molecular Pathology, Institute of Human Genetics of the Polish Academy of Sciences , Poznań, Poland .
Bogna
B
Świątek-Kościelna
1 Department of Molecular Pathology, Institute of Human Genetics of the Polish Academy of Sciences , Poznań, Poland .
Ewelina Maria
EM
Kałużna
1 Department of Molecular Pathology, Institute of Human Genetics of the Polish Academy of Sciences , Poznań, Poland .|2 Department of Medical Diagnostics, Poznań, Poland .|3 Department of Pediatric Oncology, Hematology and Bone Marrow Transplantation, University of Medical Sciences , Poznań, Poland .
Danuta
D
Januszkiewicz-Lewandowska
1 Department of Molecular Pathology, Institute of Human Genetics of the Polish Academy of Sciences , Poznań, Poland .
Jolanta
J
Rembowska
4 Department of Infectious Diseases, University of Medical Sciences , Poznań, Poland .
Iwona
I
Mozer-Lisewska
4 Department of Infectious Diseases, University of Medical Sciences , Poznań, Poland .
Iwona
I
Bereszyńska
2 Department of Medical Diagnostics, Poznań, Poland .
Katarzyna
K
Czubała
2 Department of Medical Diagnostics, Poznań, Poland .
Katarzyna
K
Dziechciowska
1 Department of Molecular Pathology, Institute of Human Genetics of the Polish Academy of Sciences , Poznań, Poland .
Joanna
J
Wysocka-Leszczyńska
2 Department of Medical Diagnostics, Poznań, Poland .
Dominika
D
Barcińska
5 Department of Preventive Medicine, University of Medical Sciences , Poznań, Poland .
Jacek
J
Wysocki
1 Department of Molecular Pathology, Institute of Human Genetics of the Polish Academy of Sciences , Poznań, Poland .
Jerzy Stanisław
JS
Nowak
D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D005260:Female; D020869:Gene Expression Profiling; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000473:pathology*; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D007963:Leukocytes, Mononuclear / Q000473:pathology; D008297:Male; D008875:Middle Aged; D060888:Real-Time Polymerase Chain Reaction; D012254:Ribavirin / Q000627:therapeutic use; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis* / Q000235:genetics; D055815:Young Adult
D000998:Antiviral Agents; D016898:Interferon-alpha; D016159:Tumor Suppressor Protein p53; D012254:Ribavirin