Antiviral activity of bacteria-derived human alpha interferons against encephalomyocarditis virus infection of mice

Abstract

Bacteria-derived human leukocyte interferon (IFN) subtypes, IFN-αA, -αB, and -αD, and two hybrid IFNs, IFN-αAD and -αDA, were examined for both in vitro and in vivo antiviral activity. Two of these materials in highly purified form (IFN-αD and -αAD) protect mice against lethal doses of encephalomyocarditis virus infection. A single dose of 1 μg of protein of IFN-αAD 3 h before infection conferred protection in both BDF1 and CD-1 mice against encephalomyocarditis virus infection, and multiple treatments with IFN-αD or IFN-αAD extend the mean survival time of infected mice. On a weight basis, IFN-αAD was approximately 100-fold more effective than IFN-αD. There is a direct correlation between the antiviral activity of the various human IFN species in L-929 cells and in mice for both single and multiple treatments before infection, but none of the cloned human IFN subtypes were effective when administered 24 h after infection. Mixtures of the two parental materials, IFN-αA and -αD, were not as protective as the hybrid molecule IFN-αAD, suggesting that IFNs with unique and altered species specificity can be produced by recombinant DNA methods.