Molecular Pathogenesis of Virus-Induced Myocardial Injury

为了阐明病毒性心肌炎的机制，很多研究都是针对宿主的免疫反应，而基于病毒本身的研究相对较少。病毒在宿主细胞中的生长是病毒发病的一个重要步骤。因此，了解心脏组织生长所需的病毒决定因素对于阐明病毒性心肌炎的发病机制非常重要。实验1两种呼肠孤病毒分离株（1型和3型）在培养的小鼠心脏细胞中的生长能力不同。哺乳动物呼肠孤病毒含有10个双链RNA基因片段的基因组。通过使用37种重组病毒（由来自两个亲本的不同基因组合的病毒组成），不同菌株在心脏细胞中生长能力的差异被定位到M1基因上。M1基因产物mu2蛋白的功能在很大程度上是未知的；然而，令人特别感兴趣的是…More M1基因的突变将病毒转化为心肌病毒。实验2两个呼肠孤病毒分离株在培养的牛主动脉内皮细胞中的生长能力也不同。通过使用24种重组病毒，观察到不同菌株在培养内皮细胞中生长能力的差异也被定位到M1基因上。两种呼肠孤病毒分离株在亲本病毒粒子的病毒外衣壳蛋白结合或蛋白水解过程中未发现差异。Northern blot分析显示，3型呼肠孤病毒感染的内皮细胞中病毒mRNA的产生减少，而1型没有。因此，我们已经确定相同的M1基因决定呼肠孤病毒在心肌细胞和内皮细胞中的生长能力。病毒感染的内皮细胞中产生的体液因子（如tnf - α、白细胞介素1和IL - 6）除了病毒在心肌细胞中的直接细胞病变作用外，还可能参与了病毒性心肌炎的发病机制。实验3:27例心肌炎、扩张型心肌病患者心肌标本（经心肌内膜活检或尸检）采用PCR方法均未检出呼肠孤病毒基因。因此，呼肠孤病毒是研究病毒如何在分子遗传水平上引起心肌炎的一个有吸引力的模型。少

Introduction To elucidate the mechanisms of viral myocarditis, much effort has been directed toward the immune response of the host, and relatively little has been done based on studies of the viruses themselves. Growth of a virus in a host cell is a major step in viral pathogenesis. Therefore, an understanding of viral determinants necessary for growth in heart tissue is important for elucidating the pathogenesis of viral myocarditis.Experiment 1 Two reovirus isolates (type 1 and type 3) differ in their capacity to grow in cultured mouse heart cells. The mammalian reoviruses contain a genome of 10 doublestranded RNA gene segments. By the use of 37 reassortant viruses (consisting of viruses with different combinations of genes derived from the two parents), difference in capacity of different strains to grow in heart cells was mapped to the M1 gene. The function of the M1 gene product, the mu2 protein, is largely unknown ; however, it is of particular interest that a mutation(s) in the … More M1 gene converts the virus to become myocarditic.Experiment 2 Two reovirus isolates also differ in their capacity to grow in cultured bovine aortic endothelial cells. By using 24 reassortant viruses, observed differences in the capacity of different strains to grow in cultured endothelial cells were also mapped to the M1 gene. No differences were detected in binding or proteolytic processing of viral outer capsid proteins of parental virions between the two reovirus isolates. Northern blot analysis showed a decreased production of viral mRNA in endothelial cells infected with type 3 reovirus, but not type 1. Thus, we have identified that the same M1 gene determines the growth capacity of reovirus in myocardial cells as well as endothelial cells. Humoral factors (such as TNF-alpha, interleukin 1, and IL 6) produced in virus-infected endothelial cells may participate in the pathogenesis of virus myocarditis in addition to the direct cytopathic effect of the virus in myocardial cells.Experiment 3 No reovirus genes were detected in myocardial samples (obtained by endomyocardial biopsy or autopsy) in 27 patients with myocarditis and dilated cardiomyopathy by the PCR method.Thus, reovirus in an attractive model in which to study how viruses cause myocarditis at a molecular genetic level. Less