Cytomegalovirus strain AD169 binds beta 2 microglobulin in vitro after release from cells

We previously reported that a host protein, beta 2 microglobulin (beta 2m) inhibited the detection of human cytomegalovirus (CMV) in urine specimens by enzyme immunoassay and postulated that beta 2m bound to the virus particle and masked the viral antigenic determinants. We report here that CMV strain AD169 grown in cell culture bound human beta 2m when this protein was added to cell culture fluids or when the virus was added to urine. Such binding was not seen with herpes simplex virus. CMV could also bind bovine beta 2m from foetal calf serum in cell culture fluids. The use of radiolabelled beta 2m in other experiments showed that CMV bound beta 2m after release from cells and that the bound beta 2m did not represent acquisition of class I HLA molecules during budding from host cell membranes. Immunoprecipitation studies showed that beta 2m was bound by two viral envelope proteins beta 2m BP1 (beta 2m-binding protein 1) and beta 2m BP2 of molecular masses 36,000 and 65,000 daltons respectively. beta 2m could not bind to separated viral proteins under reducing or non-reducing conditions. We propose that interaction of these two proteins on the viral surface is required to enable CMV to bind beta 2m.