Type I interferons inhibit hepatitis B virus replication and induce hepatocellular gene expression in cultured liver cells.
A hepatoblastoma cell line transfected with hepatitis B virus (HBV) DNA (Hep G2.2.15) was used to investigate the effects of interferons (IFNs) on HBV replication and hepatocellular gene expression. IFN-alpha 2b or -beta inhibited HBV replication transiently. In parallel, there was a decrease in the amount of HBV mRNA. Hepatitis B surface antigen and early antigen secretion were not influenced; however, their intracellular levels diminished during treatment. The cellular 2',5'-oligoadenylate synthetase activity was increased 9- to 18-fold during treatment of cells with IFN-gamma, -alpha, or -beta. The number of IFN-alpha and -beta receptors was down-regulated, while the number of IFN-gamma receptors remained constant. The expression of major histocompatibility complex class I antigens was stimulated by addition of IFN-alpha or -beta. These data show that both IFN-alpha and -beta can effectively inhibit HBV replication and induce a cellular IFN response in Hep G2.2.15 cells similar to that seen in humans.
Caselmann
W H
WH
Department of Medicine II, Klinikum Grosshadern, University of Munich, Germany.
Meyer
M
M
Scholz
S
S
Hofschneider
P H
PH
Koshy
R
R
D015088:2',5'-Oligoadenylate Synthetase / Q000378:metabolism; D006528:Carcinoma, Hepatocellular; D004273:DNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D004279:DNA, Viral / Q000235:genetics / Q000302:isolation & purification; D015870:Gene Expression / Q000187:drug effects; D006514:Hepatitis B Surface Antigens / Q000096:biosynthesis; D006515:Hepatitis B virus / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000494:pharmacology*; D016899:Interferon-beta / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology*; D007700:Kinetics; D008113:Liver Neoplasms; D017471:Receptors, Interferon / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014779:Virus Replication / Q000187:drug effects*
D004273:DNA, Neoplasm; D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D017471:Receptors, Interferon; D011994:Recombinant Proteins; D016899:Interferon-beta; D007371:Interferon-gamma; D015088:2',5'-Oligoadenylate Synthetase