MECHANISMS OF VIRAL PATHOGENESIS

哺乳动物的Mx系统包括干扰素家族 α/β诱导细胞蛋白，其中之一，Mx 1 小鼠的蛋白质，参与预防流感。 证据表明这种蛋白质是决定死亡的关键因素 或实验感染后实验小鼠的存活率， vivo是基于观察到的，在所有近交系小鼠中， 属于菌株A2 G和SL/NiA的那些在流感中存活 感染，而这些菌株中唯一小鼠 基因组编码Mx 1蛋白的Mx+等位基因。 小鼠 其他菌株含有两个Mx等位基因之一（具有编码 能力，只有截断Mx 1蛋白），他们屈服于 感染 在适当的育种实验中，Mx+等位基因 分离出对流感的抵抗力，这表明， 等位基因是控制发病的主要基因， 小鼠实验性流感感染。 其他哺乳动物物种Mx蛋白的生物功能，包括 人类就不那么清楚了。 Mx的经典遗传分析 目前在这些物种中的系统是不可行的， 不表达相应Mx蛋白的个体尚未 为了评估这些物种的Mx蛋白的作用， 选择了四种不同的方法。 首先，我们 将特异性抗Mx抗体显微注射到干扰素处理的 细胞，并正在测试这些注射的细胞对 流感感染。 其次，我们表达了多种Mx cDNA， 在适当的启动子下在Mx小鼠细胞中， 这些细胞同样对流感易感性。 第三，我们是 纯化Mx蛋白质，并测试其生物功能后， 注射到细胞中。 第四，我们正在表达Mx蛋白， 转基因小鼠，并正在测试这些小鼠的流感 易感性 现有数据表明，小鼠的Mx系统 老鼠对流感病毒有很强的抵抗力， 人的系统不太活跃。 目前的研究集中在A 详细分析了抑制病毒的机制，并对 如何在那些物种中增强Mx系统的问题， 它显示出较低的活性。

The Mx system of mammals comprises a family of interferon alpha/beta inducible cellular proteins, one of which, the Mx1 protein of mice, is involved in protection against influenza. Evidence that this protein is a crucial factor determining death or survival of a laboratory mouse after experimental infection in vivo is based on the observation that of all inbred mice, only those belonging to strain A2G and SL/NiA survive influenza infection, and that only mice of these strains contain in their genome the Mx+ allele which codes for the Mx1 protein. Mice of other strains contain either one of two Mx- alleles (with a coding capacity for only truncated Mx1 proteins), and they succumb to infection. In appropriate breeding experiments, the Mx+ allele segregates with resistance to influenza, indicating that this allele is the predominant gene controlling pathogenesis of experimental influenza infection in mice. The biofunction of Mx proteins of other mammalian species including humans is less clear. A classical genetic analysis of the Mx system in these species is not feasible at present since mutant individuals not expressing corresponding Mx proteins have yet to be found. To assess the role of the Mx proteins of these species, four different approaches have been chosen. First, we are microinjecting specific anti-Mx antibodies into interferon-treated cells, and are testing these injected cells for susceptibility to influenza infection. Second, we a re expressing various Mx cDNAs under appropriate promoters in Mx- mouse cells and are testing these cells likewise for influenza susceptibility. Third, we are purifying Mx proteins and are testing their biofunction after injection into cells. Fourth, we are expressing Mx proteins in transgenic mice and are testing these mice for influenza susceptibility. Available data indicate that the Mx system of mice and rats is highly active against influenza virus but that the Mx system of man is less active. Current research focuses on a detailed analysis of the mechanisms of virus inhibition, and on the question of how to boost the Mx system in those species in which it displays a lower activity.