Inhibitory effects on HAV IRES-mediated translation and replication by a combination of amantadine and interferon-alpha | Yang et al. Virology Journal 2010 7 212 http content 7 1 212 VIROLOGY JOURNAL SHORT REPORT Open Access Inhibitory effects on HAV IRES-mediated translation and replication by a combination of amantadine and interferon-alpha 2t 1 t 1 1 3 Lingli Yang Tomoko Kiyohara Tatsuo Kanda Fumio Imazeki Keiichi Fujiwara Verena Gauss-Muller Koji Ishii2 Takaji Wakita2 Osamu Yokosuka1 Abstract Hepatitis A virus HAV causes acute hepatitis and sometimes leads to fulminant hepatitis. Amantadine is a tricyclic symmetric amine that inhibits the replication of many DNA and RNA viruses. Amantadine was reported to suppress HAV replication and the efficacy of amantadine was exhibited in its inhibition of the internal ribosomal entry site IRES activities of HAV. Interferon IFN also has an antiviral effect through the induction of IFN stimulated genes ISG and the degradation of viral RNA. To explore the mechanism of the suppression of HAV replication we examined the effects of the combination of amantadine and IFN-alpha on HAV IRES-mediated translation HAV replicon replication in human hepatoma cell lines and HAV KRM003 genotype IIIB strain replication in African green monkey kidney cell GL37. IFN-alpha seems to have no additive effect on HAV IRES-mediated translation inhibition by amantadine. However suppressions of HAV replicon and HAV replication were stronger with the combination than with amantadine alone. In conclusion amantadine in combination of IFN-alpha might have a beneficial effect in some patients with acute hepatitis A. Short report Hepatitis A virus HAV a member of the family Picor-naviridae causes acute hepatitis and occasionally fulminant hepatitis a life-threatening disease. As the broad epidemiological picture of hepatitis A changes the public health importance of this disease is being increasingly recognized 1 . It is a significant cause of morbidity worldwide although the mortality rate due to hepatitis A is low improved intensive care and .
