SUMMARYPrevious reports have provided evidence for the ability of human cytomegalovirus (HCMV) to bind the host protein/~z microglobulin (fl2m) from body fluids or culture mediung, and thus enhance infectivity of the virus, both by evasion of immune neutralization and the capacity to employ the bound flzm for attachment to the host cell. Immunocytochemical techniques and negative stain electron microscopy were used to identify the ultrastructural components of HCMV involved in its interaction with f12 m. Probes comprising colloidal gold coupled to//zm were seen to bind not to the envelope as previously suspected, but to material closely surrounding the nucleocapsids. It is postulated that the tegument proteins of HCMV, via their capacity to bind f12 m, play an important role in the preservation of infectivity of disrupted virions by enabling unenveloped capsids to bind to cells and gain entry by a pathway other than that normally taken by intact virions.In recent years, interesting information has come to light regarding the affinity of human cytomegalovirus (HCMV) for f12 microglobulin (fl/m). McKeating et al. (1985) reported that their ELISA for the detection of HCMV failed to detect the virus in fresh urine samples, but that upon storage at 4 °C for 1 to 2 weeks initially negative samples became ELISA-positive. They postulated the presence of an inhibitory substance in fresh urine which might be destroyed upon storage, and subsequently McKeating et al. (1986) identified fl2m as such an inhibitor. Furthermore, flzm was shown to bind to HCMV strain AD169 grown in cell culture when fl2m had been added to the culture fluids (Grundy et al., 1987a), but only after the release of the virions from the cell. McKeating et al. (1987) demonstrated that the binding of fl2m to urinary HCMV was also able to prevent neutralization of the virus by various neutralizing antisera, and because the presence of flzm could be demonstrated only in the Triton X-100-soluble fraction of HCMV harvested from urine, and not in the Triton-insoluble fraction, they concluded that fl2m was associated with the envelope, and possibly masked antigenic sites necessary for neutralization. Further studies (Grundy et al., 1987 b) demonstrated that the binding of fl2m to HCMV enhanced the infectivity of the virus and the authors postulated that bound fl2m assisted in the attachment of the virus to the host cell. It was also shown that fl2m and HCMV compete for binding sites on fibroblasts, where fl2m is normally non-covalently bound to the heavy chain of class I HLA molecules. As a result of evidence which showed that fl2m-coated HCMV could bind more efficiently to Raji cells (which express class I HLA molecules) than to Daudi cells (which lack these determinants), it was postulated that HCMV could use class I HLA molecules as a virus receptor and displace fl2m from the fl2m-HLA heavy chain dimers present on the cell surface.Although many of these earlier findings were based on the assumption that fl2m was able to bind to viral glycoproteins on the v...