Recombinant human interferon-gamma inhibits adenovirus multiplication without modifying viral penetration

We have recently reported that adenovirus replication is inhibited by human recombinant interferon-gamma, but not by recombinant interferon-alpha, in a dose-dependent manner. The aim of this study was to determine whether the antiviral effect of recombinant interferon-gamma could be linked to interferon-induced alteration at the membrane level, inhibiting either adenovirus penetration of or release from WISH cells. Adsorption and penetration were investigated with an 125I-labelled adenovirus binding assay. To test defective virus release, the presence of newly synthesized virus proteins in the cytoplasmic and nuclear compartments was investigated. Binding studies showed that interferons-gamma and -alpha did not modify adenovirus attachment and penetration. Interferon-gamma but not interferon-alpha inhibited hexon protein synthesis in the cytosol as well as its accumulation in the nuclear compartment. The synthesis of polypeptides III, IV and VI was also inhibited. In cells infected before interferon-gamma treatment, its addition could be delayed up to 2 h after the infection to produce an inhibition of virus yield greater than 1 log10 unit (90% inhibition). We conclude that interferon-gamma acts on an intracellular step before or at adenovirus protein synthesis, probably through a mechanism not shared with interferon-alpha.