beta2 Microglobulin Enhances the Infectivity of Cytomegalovirus and When Bound to the Virus Enables Class I HLA Molecules To Be Used as a Virus Receptor

Abstract

Summary We have previously demonstrated that human cytomegalovirus (CMV) binds the host protein β2 microglobulin (β2m) from body fluids or from cell culture media. In this report we have examined the effect of the β2m on viral infectivity. We have shown that the addition of human purified β2m, or a fraction of foetal calf serum corresponding to bovine β2m, 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 β2m by CMV increased its infectivity. We have shown that CMV and β2m compete for binding sites on fibroblasts. As the main binding site on cells for β2m 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 β2m-coated CMV was significantly higher to Raji cells than to Daudi cells. Furthermore, CMV could compete with β2m 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 β2m, CMV has the capacity to displace β2m from the class I HLA heavy chain-β2m dimer on the cell surface and bind to cells. The fact that β2m enhances infectivity suggests that such binding leads to productive infection of cells.