Bacteria-derived human leukocyte interferon (IFN) subtypes, IFN-alpha A, -alpha B, and -alpha D, and two hybrid IFNs, IFN-alpha AD and -alpha DA, were examined for both in vitro and in vivo antiviral activity. Two of these materials in highly purified form (IFN-alpha D and -alpha D) protect mice against lethal doses of encephalomyocarditis virus infection. A single dose of 1 microgram of protein of IFN-alpha D 3 h before infection conferred protection in both BDF1 and CD-1 mice against encephalomyocarditis virus infection, and multiple treatments with IFN-alpha D or IFN-alpha AD extend the mean survival time of infected mice. On a weight basis, IFN-alpha AD was approximately 100-fold more effective than IFN-alpha D. 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-alpha A and -alpha D, were not as protective as the hybrid molecule IFN-alpha AD, suggesting that IFNs with unique and altered species specificity can be produced by recombinant DNA methods.
Animals Cattle