IFN-tau treatment in mice infected with cowpox virus

描述(由研究人员提供)：这个SBIR第一阶段项目将评估口服干扰素-tau(T)(INF-tau)对小鼠致死性牛痘病毒感染的影响。治疗的效果将基于降低肺部病毒滴度和防止感染小鼠死亡。2‘，5’-寡腺苷合成酶(OAS)的诱导和自然杀伤(NK)细胞活性的诱导也将被确定，因为这些活性被认为介导了干扰素-tau的抗病毒作用。在这个拟议的项目中，将在感染致死性牛痘病毒的小鼠身上测试口服干扰素-t的潜在用途。预防和治疗方案都将进行评估。 干扰素-tau具有口服生物活性。当口服时，干扰素-tau在小鼠和人类中诱导OAS(Pepgen的未发表数据)。与重组人干扰素-α相比，干扰素-t和重组人凝血因子-α均能在很低浓度下增强绵羊自然杀伤细胞(NK)杀伤人靶细胞的活性。干扰素-tau还被证明能够抑制人类乳头瘤病毒、人类免疫缺陷病毒、人类乙肝病毒和猫免疫缺陷病毒以及小鼠泰勒氏病毒的病毒复制。除了口服方便外，干扰素-tau的优势之一是副作用低，毒性低。 在生物恐怖情况下，天花病毒预计将通过气雾剂传播，接触到天花病毒的人数可能非常多。此外，在这种情况下，人口可能面临反复和长期接触该病毒。因此，重要的是不仅要治疗感染者，努力挽救他们的生命，而且要通过阻止新的感染和二次传播来遏制潜在的流行病。一种既能预防又能治疗、易于使用(口服)且毒性较小的药物将是理想的。

DESCRIPTION (provided by investigator): 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 When administered orally, IFN-tau induces OAS in mice and humans (Pepgen's unpublished data).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.