Interferon type I gene expression in chronic hepatitis C.
Hepatitis C virus (HCV) frequently causes chronic liver disease. The cause of viral persistence might be an inappropriate type I interferon (IFN) induction. To analyze the host's IFN response in chronic hepatitis C, we measured the transcription level of type I IFN genes as well as type I IFN-regulated genes in liver tissue and corresponding blood samples from patients with chronic hepatitis C, nonviral liver diseases, and a suspected but later excluded liver disease. Competitive and real-time RT-PCR assays were used to quantify the messenger RNA (mRNA) levels of all known IFN-alpha, IFN-beta, and IFN-lambda genes and those of some IFN-regulated genes. We failed to detect any hepatic type I IFN mRNA induction, although liver tissue of chronic hepatitis C patients contained high numbers of some type I IFN-inducible effector mRNA molecules. Analysis of peripheral blood samples, however, showed a clear type I IFN induction. Parallel experiments employing HCV replicon cell lines revealed that replication of HCV RNA is not sufficient to induce any type I IFN nor to induce directly type I IFN-regulated genes such as MxA. In conclusion, our data provide evidence for the absence of an induction of type I IFN genes by HCV in the human liver and argue for a further development of type I IFN-based therapies.
Mihm
Sabine
S
Division of Gastroenterology and Endocrinology, Department of Internal Medicine, Georg-August-Universität, Göttingen, Germany. smihm@med.uni-goettingen.de
Frese
Michael
M
Meier
Volker
V
Wietzke-Braun
Perdita
P
Scharf
Jens-Gerd
JG
Bartenschlager
Ralf
R
Ramadori
Giuliano
G
D000293:Adolescent; D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000821:virology; D045744:Cell Line, Tumor; D005260:Female; D015967:Gene Expression Regulation, Viral; D016174:Hepacivirus / Q000235:genetics* / Q000254:growth & development; D019698:Hepatitis C, Chronic / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D022781:Hepatocytes / Q000821:virology; D006801:Humans; D007370:Interferon Type I / Q000235:genetics* / Q000378:metabolism; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D012367:RNA, Viral / Q000032:analysis; D012093:Replicon / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic; D014779:Virus Replication / Q000502:physiology
D007370:Interferon Type I; D012333:RNA, Messenger; D012367:RNA, Viral