Enhanced viral resistance in transgenic mice expressing the human beta 1 interferon

Recombinant plasmids pMTIF-beta 1A and pMTIF-beta 1B were constructed by fusing the metallothionein I promoter-regulatory region to the human beta 1 interferon (HuIFN-beta 1) gene. These linearized fusion genes were then introduced into mouse germ lines by zygote microinjection. The chromosomal integration and the germ line transmission of the injected DNA sequences in the resulting transgenic mice were detected by DNA dot blot and Southern transfer hybridizations. The sera of at least two strains of metallothionein/HuIFN transgenic mice were found to protect human WISH cells against vesicular stomatitis virus infection, and this activity could be neutralized by preincubation with anti-HuIFN-beta 1 antibody. These transgenic mice demonstrated significantly enhanced resistance to pseudorabies virus compared with nontransgenic mice when inoculated with pseudorabies virus. The level of resistance seemed to correlate with the concentrations of HuIFN-beta 1 in serum. These transgenic mice may be used as models to study IFN-induced responses and may serve as prototypes to generate disease-resistant animals.