Intracellular signalling and antiviral effects of interferons.

More than 4 decades after their discovery, interferons are used now in daily clinical practice for the treatment of chronic viral hepatitis, multiple sclerosis, chronic granulomatous disease, and malignant disease such as hairy cell leukaemia, chronic myeloid leukaemia, Kaposi's sarcoma, multiple myeloma and malignant melanoma. In general, treatment with interferons is successful in only a fraction of the patients suffering from these diseases. The reasons for treatment failures in many patients are not understood a present. The discovery of the Jak-Stat pathway as the principal signalling pathway for interferons opens new research options for a better understanding of interferon resistance in various diseases. Defective Jak-Stat signal transduction has now been described in cells expressing HBV proteins, in cells expressing HCV proteins, and in cell lines derived from malignant melanomas. A better understanding of these signalling defects might lead to new therapeutic strategies making interferons more effective in a larger percentage of patients.