Generation and characterization of recombinant coxsackievirus replicons for prevention of virus-induced heart disease

直到今天，临床上还没有针对柯萨奇病毒B3（CVB 3）诱导的急性和慢性人类心脏炎症的病毒特异性预防或治疗方法。因此，寻找新的有效方法预防病毒性心肌炎是本研究项目的目标。一种预防病毒感染的新策略是基于开发表达精氨酸的重组病毒载体。病毒基因组内免疫调节蛋白干扰素-g（IFN-g）的同时表达影响免疫途径的正常模式，并通过直接和间接机制引起对随后的致死性感染的强烈保护。然而，直到现在还不清楚这种保护是如何产生的。因此，本研究项目的重点是以下问题：·哪些代谢途径参与IFN-g的直接抗病毒活性？·IFN-g的间接保护作用是如何诱导的？·IFN-g效应是病毒特异性的吗？

Until today no virus-specific prophylactic or therapeutic procedures for coxsackievirus B3 (CVB3)-induced acute and chronic human cardiac inflammation are in clinical use. Therefore, the search for new effective methods to prevent virus-caused myocarditis is the goal of this research project. A novel strategy to prevent viral infection is based on the development of cytokine-expressing recombinant virus vectors. The simultaneous expression of the immunoregulatory protein interferon-g (IFN-g) from within the viral genome influences the normal pattern of immune pathways and caused an intense protection against subsequent lethal infections via direct and indirect mechanisms. However, until now it is not clear how this protection is induced. Therefore, this research project is focused on the following questions: · Which metabolic pathways are involved in the direct antiviral activity of IFN-g ? · How is the indirect protective effect of IFN-g induced? · Is the IFN-g effect virus-specific?