Inhibitory effects on HAV IRES-mediated translation and replication by a combination of amantadine and interferon-alpha.
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.
Yang
Lingli
L
Department of Medicine and Clinical Oncology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
Kiyohara
Tomoko
T
Kanda
Tatsuo
T
Imazeki
Fumio
F
Fujiwara
Keiichi
K
Gauss-Müller
Verena
V
Ishii
Koji
K
Wakita
Takaji
T
Yokosuka
Osamu
O
D000547:Amantadine / Q000494:pharmacology*; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D004347:Drug Interactions; D004847:Epithelial Cells / Q000821:virology; D030041:Hepatitis A virus / Q000187:drug effects* / Q000502:physiology*; D022781:Hepatocytes / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D014176:Protein Biosynthesis / Q000187:drug effects*; D014779:Virus Replication / Q000187:drug effects*
D000998:Antiviral Agents; D016898:Interferon-alpha; D000547:Amantadine
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