INTERFERONS, MX-GENES, AND RESISTANCE TO INFLUENZA-VIRUS
INTERFERONS, MX-GENES, AND RESISTANCE TO INFLUENZA-VIRUS
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DOI：
10.1164/ajrccm/152.4_pt_2.s67
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发表时间：
1995-10-01
影响因子：
24.7
通讯作者：
HORISBERGER, MA
中科院分区：
文献类型：
--
作者：
HORISBERGER, MA
人类流感主要是上呼吸道和中央呼吸道感染。干扰素（IFN）系统似乎具有限制病毒传播和启动恢复的作用，在原发性感染的T细胞和B细胞反应的发展之前。所有对IFN的细胞反应都是由与细胞表面受体的相互作用引起的，这些受体触发许多细胞基因的表达。在IFN诱导的基因产物中，Mr蛋白由于具有抗流感病毒和可能抗其它病毒的活性而引起人们的广泛关注。Mx蛋白是具有内在GTP酶活性的鸟苷三磷酸（GTP）结合蛋白。它们似乎通过改变病毒复制途径沿着所需的细胞功能来间接对抗病毒。在小鼠中，Mx1蛋白已被证明是必要的，足以防止流感病毒感染，因为抵抗不需要功能正常的免疫系统。在人类中，MxA蛋白具有抗流感病毒的抗病毒活性。MxA蛋白与IFN系统中涉及的几种其他蛋白一起编码在染色体21的长臂的远端部分上。患有唐氏综合征（21三体）的患者具有增加的MxA蛋白表达，并且由于基因剂量效应，他们的细胞在体外显示出对IFN的敏感性增加。然而，这些患者比正常人更容易患上呼吸道感染。这种易感性与免疫系统的缺陷有关。因此，在人类中诱导MxA似乎不足以防止流感传播，并且与鼠MR系统相反，功能性免疫系统对于保护是必要的。
Human influenza is primarily an infection of the upper respiratory tract and central airways. The interferon (IFN) system appears to have a role in limiting viral spread and initiating recovery before the development of T-cell and B-cell responses in primary infection. All cellular responses to IFNs result from interaction with cell surface receptors that trigger the expression of a number of cellular genes. Among the IFN-inducible gene products, the Mr proteins have attracted much attention because they have potential activity against influenza virus and possibly against other viruses. Mx proteins are guanosine triphosphate (GTP)-binding proteins with intrinsic GTPase activity. They seem to act indirectly against viruses by modifying cellular functions needed along the viral replication pathway. In mice the Mx1 protein has been shown to be necessary and sufficient to protect against influenza virus infection because the resistance does not require a functioning immune system. In humans the MxA protein has antiviral activities against influenza viruses. The MxA protein is encoded on the distal part of the long arm of chromosome 21 together with several other proteins implicated in the IFN system. Patients with Down's syndrome (trisomy 21) have an increased expression of MxA protein, and their cells display an increased sensitivity to IFNs in vitro because of gene dosage effects. These patients, however, are more susceptible to upper respiratory infection than normal individuals. This susceptibility has been related to deficiencies in the immune system. Therefore, induction of MxA in man does not seem sufficient to prevent influenza spreading, and, in contrast to the murine Mr system, a functioning immune system is necessary for protection.