A major difference between vaccine and wild-type strains of measles virus (MV) in vitro is the wider cell specificity of vaccine strains, resulting from the receptor usage of the hemagglutinin (H) protein. Wild-type H proteins recognize the signaling lymphocyte activation molecule (SLAM) (CD150), which is expressed on certain cells of the immune system, whereas vaccine H proteins recognize CD46, which is ubiquitously expressed on all nucleated human and monkey cells, in addition to SLAM. To examine the effect of the H protein on the tropism and attenuation of MV, we generated enhanced green fluorescent protein (EGFP)-expressing recombinant wild-type MV strains bearing the Edmonston vaccine H protein (MV-EdH) and compared them to EGFP-expressing wild-type MV strains. In vitro, MV-EdH replicated in SLAM ؉ as well as CD46 ؉ cells, including primary cell cultures from cynomolgus monkey tissues, whereas the wild-type MV replicated only in SLAM ؉ cells. However, in macaques, both wild-type MV and MV-EdH strains infected lymphoid and respiratory organs, and widespread infection of MV-EdH was not observed. Flow cytometric analysis indicated that SLAM ؉ lymphocyte cells were infected preferentially with both strains. Interestingly, EGFP expression of MV-EdH in tissues and lymphocytes was significantly weaker than that of the wild-type MV. Taken together, these results indicate that the CD46-binding activity of the vaccine H protein is important for determining the cell specificity of MV in vitro but not the tropism in vivo. They also suggest that the vaccine H protein attenuates MV growth in vivo. Measles remains a major cause of childhood morbidity and mortality worldwide especially in developing countries in spite of significant progress in global measles control programs. Measles virus (MV), belonging to the genus Morbillivirus of the family Paramyxoviridae, is an enveloped virus with a nonsegmented negative-strand RNA genome (11). The MV genome encodes 6 structural proteins: the nucleocapsid (N), phospho (P), matrix (M), fusion (F), hemagglutinin (H), and large (L) proteins. Two envelope glycoproteins, the F and H proteins, initiate infection of the target cells via binding of the H protein to its cellular receptors. Therefore, the H protein is of primary importance for determining the cell specificity of MV (22).The Edmonston strain of MV was isolated in 1954 by using a primary culture of human kidney cells (7). The Edmonston strain was subsequently adapted in a variety of cells, including chicken embryo fibroblasts, to enable the production of attenuated live vaccines, which are currently used worldwide (27). These live, attenuated MV strains are safe and induce strong cellular and humoral immune responses against MV. The Edmonston vaccine strain is no longer pathogenic in monkey models (2, 7, 37, 39). In contrast, wild-type MV strains isolated and passaged in B95a cells induce clinical signs resembling those of human measles in experimentally infected cynomolgus and rhesus monkeys (15, 16).A major difference betwe...

Measles virus (MV) is an enveloped negative strand RNA virus belonging to the family of Paramyxoviridae, genus Morbillivirus, and causes one of the most contagious diseases in humans. Experimentally infected non-human primates are used as animal models for studies of the pathogenesis of human measles. We established a reverse genetics system based on a highly pathogenic wild-type MV. Infection of monkeys with recombinant MV strains generated by reverse genetics enabled analysis of the molecular basis of MV pathogenesis. The essential in vivo function of accessory genes was indicated by infecting monkeys with recombinant MV strains deficient in the expression of accessory genes. Furthermore, recombinant wild-type MV strains expressing enhanced green fluorescent protein enabled visual tracking of MV-infected cells in vitro and in vivo. To date, three different molecules have been identified as receptors for MV. Signaling lymphocyte activation molecule (SLAM, also called CD150), expressed on immune cells, is a major receptor for MV. CD46, ubiquitously expressed in all nucleated cells in humans and monkeys, is a receptor for vaccine and laboratory-adapted strains of MV. The newly identified nectin-4 (also called poliovirus-receptor-like-4) is an epithelial cell receptor for MV. However, recent findings have indicated that CD46 acts as an MV receptor in vitro but not in vivo. The impact of the receptor usage of MV in vivo on the disease outcome is now under investigation.

Measles vaccines are highly effective and safe; however, the mechanism(s) underlying their attenuation has not been well understood. In this study, type I IFNs (IFN-α and IFN-β) induction in macaques infected with measles virus (MV) strains was examined. Type I IFNs were not induced in macaques infected with wild-type MV. However, IFN-α was sharply induced in most macaques infected with recombinant wild-type MV bearing the hemagglutinin (H) protein of the Edmonston vaccine strain. These results indicate that the H protein of MV vaccine strains may have a role in MV attenuation.