BETA-2 MICROGLOBULIN ENHANCES THE INFECTIVITY OF CYTOMEGALOVIRUS AND WHEN BOUND TO THE VIRUS ENABLES CLASS-I HLA MOLECULES TO BE USED AS A VIRUS RECEPTOR
BETA-2 MICROGLOBULIN ENHANCES THE INFECTIVITY OF CYTOMEGALOVIRUS AND WHEN BOUND TO THE VIRUS ENABLES CLASS-I HLA MOLECULES TO BE USED AS A VIRUS RECEPTOR
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DOI：
10.1099/0022-1317-68-3-793
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发表时间：
1987-03-01
影响因子：
3.8
通讯作者：
GRIFFITHS, PD
中科院分区：
文献类型：
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作者：
GRUNDY, JE;MCKEATING, JA;GRIFFITHS, PD
我们先前已经证明人巨细胞病毒（CMV）结合来自体液或来自细胞培养基的宿主蛋白β 2微球蛋白（β 2 m）。在本报告中，我们已经检查了β 2 m对病毒感染性的影响。我们已经表明，与来自在无血清培养基中生长的细胞的感染性细胞外CMV的量相比，向培养基中加入人纯化的β 2 m或对应于牛β 2 m的胎牛血清部分增加了感染性细胞外CMV的量。代谢标记实验表明，这种效应不是由于细胞外病毒量的增加，而是由于细胞外液中存在的病毒的感染性增加。我们得出结论，CMV与β 2 m的结合增加了其感染性。我们已经表明CMV和β 2 m竞争成纤维细胞上的结合位点。由于细胞上β 2 m的主要结合位点是I类HLA重链，我们比较了CMV与表达或缺乏I类HLA分子表达的Raji和Daudi细胞系的结合。放射性标记的β 2 m包被的CMV与Raji细胞的结合显著高于与Daudi细胞的结合。此外，CMV可以与β 2 m竞争结合Raji细胞，尽管相反的情况并不成立。这些结果表明，CMV可以使用I类HLA分子作为病毒受体。我们提出，当用β 2 m包被时，CMV具有从细胞表面上的I类HLA重链-β 2 m二聚体置换β 2 m并结合细胞的能力。β 2 m增强感染性的事实表明这种结合导致细胞的生产性感染。
We have previously demonstrated that human cytomegalovirus (CMV) binds the host protein .beta.2microglobin (.beta.2m) from body fluids or from cell culture media. In this report we have examined the effect of the .beta.2m on viral infectivity. We have shown that the addition of human purified .beta.2m, or a fraction of foetal calf serum corresponding to bovine .beta.2m, to culture medium increased the amount of infectious extracellular CMV, compared to that from cells grown in serum-free medium. Metabolic labelling experiments demonstrated that this effect was not due to an increase in the amount of extracellular virus but to an increase in the infectivity of the virus present in extracellular fluids. We concluded that the binding of .beta.2m by CMV increased its infectivity. We have shown that CMV and .beta.2m compete for binding sites on fibroblasts. As the main binding site on cells for .beta.2m is the class I HLA heavy chain we compared the binding of CMV to the Raji and Daudi cell lines which express or lack expression of class I HLA molecules. The binding of radiolabelled .beta.2m-coated CMV was significantly higher to Raji cells than to Daudi cells. Furthermore, CMV could compete with .beta.2m for binding to Raji cells, although the reverse was not true. These results demonstrate that CMV can use class I HLA molecules as a virus receptor. We propose that when coated with .beta.2m, CMV has the capacity to displace .beta.2m from the class I HLA heavy chain-.beta.2m dimer on the cell surface and bind to cells. The fact that .beta.2m enhances infectivity suggests that such binding leads to productive infection of cells.