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

Abstract

Bacteria[Escherichia coli]-derived human leukocyte interferon (IFN) subtypes, IFN-.alpha.A, -.alpha.B and -.alpha.D, and 2 hybrid IFN, IFN-.alpha.AD and -.alpha.DA, were examined for in vitro and in vivo antiviral activity. Two of these materials in highly purified form (IFN-.alpha.D) -.alpha.AD) protect mice against lethal doses of encephalomyocarditis virus infection. A single dose of 1 .mu.g of protein of IFN-.alpha.AD 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 extended the mean survival time of infected mice. On a weight basis, IFN-.alpha.AD was .apprx. 100-fold more effective than IFN-.alpha.D. There was 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 2 parental materials, IFN-.alpha.A and -.alpha.D, were not as protective as the hybrid molecule IFN-.alpha.D, suggesting that IFN with unique and altered species specificity can be produced by recombinant DNA methods.