Measles is the seventh leading cause of childhood mortality worldwide. Currently 30–40 million measles infections occur each year, leading to 1–2 million deaths. In addition to causing an acute respiratory infection, measles is associated with a profound, transient suppression of cell-mediated immunity. This immunosuppression contributes to the major complications of measles: pneumonia, diarrhea, and other secondary infections. In rare cases, measles can also cause encephalitis and persistent infection of the central nervous system (Griffin and Bellini, 1996). A live-attenuated vaccine controls measles infection in industrialized countries, and measles has been targeted by the World Health Organization for global eradication following the eradication of poliovirus. Nevertheless, measles is endemic in many parts of the world, and recurring outbreaks still occur in industrialized regions for a variety of reasons: First, measles virus (MV) is one of the most contagious infectious agents known, and high levels of vaccine coverage are required to prevent virus circulation in a population. Second, young infants are resistant to vaccination with the attenuated vaccine strain of MV due to maternal antibody interference. Third, while individuals infected with wild-type measles show lifelong immunity, mounting evidence suggests that waning immunity in adult vaccine recipients may allow subclinical infection by MV, providing another source of virus for infants or other susceptible individuals (Clements and Cutts, 1995). Thus, while eradication is a primary goal, frequent reemergences in countries such as the United States (Alaska, 1998), Brazil (1997), Japan (1997–1998), The Netherlands (1999–2000), and Afghanistan (2000) are testament to the challenges that remain for understanding the pathogenesis and methods of effective control of measles.

Interactions between viruses and cell-surface receptors are a major determinant of virus tropism and pathogenesis. Since the identification of CD46 (membrane cofactor protein; MCP) as a major receptor for measles virus in 1993, a great number of studies have sought to understand the nature of the CD46–measles interaction. In the early 1990s, the few virus receptors which were known had been identified because of a very restricted tropism to certain cell types. In this way the CD4 molecule had been shown to be the major receptor for HIV-1 and the CD21 molecule the major receptor for Epstein–Barr virus. The identification of a virus receptor with a ubiquitous tissue distribution in its host species, the poliovirus receptor (PVR), inspired a similar hunt for the MV receptor. One of the successful strategies used for the identification of both the polio and measles virus receptors involved the generation of an anticellular monoclonal antibody-inhibiting infection followed by the purification, microsequencing, and identification of the cellular protein recognized by the antibody (Naniche et al., 1993). Another approach to identify the MV receptor used somatic cell hybrids to identify the chromosome (s) which could confer MV sensitivity to a nonpermissive cell (Dorig et al., 1993). The expression of CD46 in murine cells was demonstrated to be necessary and sufficient to allow entry and syncytia formation following expression of both the Edmonston MV hemagglutinin (H) and fusion (F) proteins. Other cellular factors, however, appear to be necessary for the virus to efficiently complete its life cycle in the host cell. The relatively weak ability of MV to replicate in murine cells has been confirmed in cell lines and in transgenic mice expressing CD46. A recent study has suggested that poor budding of MV from murine CD46-expressing fibroblasts …