This SBIR Phase I project will evaluate the effects of orally administered Interferon-tau (t) (INF-tau) on lethal cowpox virus infection in mice. The effect of treatment will be based on the reduction of viral titer in the lungs and prevention of death of the infected mice. Induction of 2', 5'-oligoadenylate synthetase (OAS) and induction of natural killer (NK) cell activity, will also be determined as these activities are thought to mediate the anti-viral effects of IFN-tau. In this proposed project, the potential utility of oral IFN-t will be tested in mice infected with lethal cowpox virus. Both prophylactic and therapeutic protocols will be evaluated. IFN-tau is orally bioactive. When administered orally, IFN-tau induces OAS in mice and humans (Pepgen's unpublished data). When compared with recombinant human IFN-alpha, both IFN-t and rhlFN-alpha could increase the sheep Natural Killer (NK) activity to kill human target cells at very low concentration. IFN-tau also demonstrated to be able to suppress viral replication of human papillomavirus, human immunodeficiency virus, human hepatitis B virus and feline immunodeficiency virus, and murine Theiler's virus. In addition to its convenience of oral intake, one of IFN-tau's advantages is its low side effect and low toxicity profile. In a bioterrorist scenario smallpox virus is expected to be transmitted by aerosol and the number of exposed individuals could be very large. Moreover, under such a scenario the population could face repeated and prolonged exposure to the virus. Therefore, it will be important not only to treat infected individuals in an effort to save their lives but also to curtail a potential epidemic by blocking new infections and secondary transmission. A drug which can provide both prophylactic and therapeutic benefit, with easy use (oral administration) and less toxic would be ideal.
Thesaurus Terms: Poxviridae, antiviral agent, drug screening /evaluation, immunotherapy, interferon, nonhuman therapy evaluation, oral administration enzyme activity, enzyme induction /repression, leukocyte activation /transformation, ligase, natural killer cell, receptor binding, smallpox virus HeLa cell, animal genetic material tag, bioterrorism /chemical warfare, data collection methodology /evaluation, laboratory mouse, polymerase chain reaction
