Henke Andreas, Jarasch Nadine, Martin Ulrike, Wegert Jenny, Wildner Anja, Zell Roland, Wutzler Peter
Institute of Virology and Antiviral Therapy, Medical Center, Friedrich Schiller University, Hans-Knöll-Strasse 2, D-07745 Jena, Germany.
Int J Med Microbiol. 2008 Jan;298(1-2):127-34. doi: 10.1016/j.ijmm.2007.08.010. Epub 2007 Sep 25.
Cardiovascular diseases are the major cause of human death and have been linked to many different risk factors. Among them, coxsackievirus B3 (CVB3), as a member of the enterovirus group, is one of the most important infectious agents of virus-induced myocarditis. Despite the fact that the molecular structure of this pathogen has been characterized very precisely, there is no virus-specific preventive or therapeutic procedure against CVB3-induced heart disease in clinical use today. A promising approach to prevent CVB3-caused myocarditis represents the mutation of the viral genome in a way that coding sequences of cytokines are integrated into the viral RNA. Recombinant cytokine-expressing CVB3 variants were established to increase the local cytokine concentration and to modulate TH1-/TH2-specific immune responses. Especially protective against CVB3-induced murine myocarditis is the application of an interferon-gamma (IFN-gamma)-expressing recombinant coxsackievirus variant. The local and simultaneous expression of an immuno-relevant cytokine by the virus itself induces a strong and long-lasting immune response which protects laboratory animals against lethal infections.
心血管疾病是人类死亡的主要原因，并且与许多不同的风险因素有关。其中，柯萨奇病毒B3（CVB3）作为肠道病毒组的一员，是病毒诱导性心肌炎最重要的感染因子之一。尽管这种病原体的分子结构已被非常精确地表征，但目前临床上尚无针对CVB3诱导性心脏病的病毒特异性预防或治疗方法。一种有前景的预防CVB3引起的心肌炎的方法是对病毒基因组进行突变，使细胞因子的编码序列整合到病毒RNA中。已建立表达重组细胞因子的CVB3变体，以增加局部细胞因子浓度并调节TH1/TH2特异性免疫反应。表达干扰素-γ（IFN-γ）的重组柯萨奇病毒变体对CVB3诱导的小鼠心肌炎具有特别的保护作用。病毒自身局部且同时表达免疫相关细胞因子会诱导强烈且持久的免疫反应，从而保护实验动物免受致命感染。
