Viral infections stimulate the transcription of
interferon type I, which includes IFN-alfa (IFN-alpha) (13 subtypes) and IFN-beta (a single substance). Hepatitis C virus (HCV)
infection is remarkable by its ability to evade host
antiviral defenses; however, there is little information as to whether endogenous IFN is activated or not in this disease. Additionally, despite the fact that the various IFN-alpha subtypes may differ in
biological activity, there are no data concerning the IFN-alpha subtypes specifically expressed in normal and diseased liver tissue. Thus, we have analyzed the IFN-alpha subtypes and the
mRNA levels of type I IFNs in samples of normal liver tissue and in liver from patients with
chronic hepatitis C. Similar studies were performed in peripheral blood mononuclear cells (PBMC) from patients and controls. After amplification and cloning of IFN-alpha
cDNA, we observed that 98 of the 100 clones from normal liver tissue corresponded to the
IFN-alpha5 subtype. However, in livers with
chronic hepatitis C and in PBMC from controls and patients, a variety of subtypes, in addition to
IFN-alpha5, were detected, suggesting a participation of infiltrating leukocytes in the production of IFN-alpha in livers with
chronic hepatitis C. As compared with controls, patients with
chronic hepatitis C showed a significant increase in IFN-beta
mRNA in both the liver and PBMC, while IFN-alpha
mRNA was significantly increased in PBMC but markedly reduced in liver tissue. In conclusion,
IFN-alpha5 is the sole IFN-alpha subtype expressed in normal liver tissue. The hepatic levels of IFN-alpha are reduced in
chronic hepatitis C, an event that may favor viral persistence.