Recombinant Human Interferon-  Inhibits Adenovirus Multiplication without Modifying Viral Penetration

Abstract

SUMMARYWe have recently reported that adenovirus replication is inhibited by human recombinant interferon-y, but not by recombinant interferon-cq in a dose-dependent manner. The aim of this study was to determine whether the antiviral effect of recombinant interferon-~ 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 12SI-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-7 and -a did not modify adenovirus attachment and penetration. Interferon-y but not interferon-a 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-7 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-y acts on an intracellular step before or at adenovirus protein synthesis, probably through a mechanism not shared with interferon-a.

Regulation of macrophage growth and antiviral activity by interferon-gamma.

“…The Mx gene product involved in natural resistance to influenza infection in mice is specifically induced by IFN-ct, but not IFN-), (45). On the other hand, it appears that adenoviruses can be inhibited by IFN-7, but not IFN-ct (30). While we have no formal proof that the antiviral effects of IFN-3, are mediated through dsRNA-dependent P1/elF-o~ protein kinase or 2',5'-(A)n synthetase, our results are consistent with the interpretation that either or both of those pathways may be involved in resistance to VSV and EMC replication, although our data would suggest that IFN-c~ and IFN-~, must utilize different pathways to regulate these genes.…”

Sensitivity of subgroup F adenoviruses to interferon

“…However, they have been shown to be susceptible to recombinant human ~,-IFN but not recombinant ~-and 13-IFN, indicating differences in the mechanism of antiviral action [27][28][29].…”