title: Wild-type measles virus with the hemagglutinin protein of the edmonston vaccine strain retains wild-type tropism in macaques.
abstract: 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.
authors.affiliation: Department of Infection Biology, Division of Biomedical Science, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan. ktakeuch@md.tsukuba.ac.jp
authors.forename: Kaoru
authors.initials: K
authors.lastname: Takeuchi
authors.forename: Noriyo
authors.initials: N
authors.lastname: Nagata
authors.forename: Sei-Ich
authors.initials: SI
authors.lastname: Kato
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Ami
authors.forename: Yuriko
authors.initials: Y
authors.lastname: Suzaki
authors.forename: Tadaki
authors.initials: T
authors.lastname: Suzuki
authors.forename: Yuko
authors.initials: Y
authors.lastname: Sato
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Tsunetsugu-Yokota
authors.forename: Kazuyasu
authors.initials: K
authors.lastname: Mori
authors.forename: Nguyen
authors.initials: N
authors.lastname: Van Nguyen
authors.forename: Hideki
authors.initials: H
authors.lastname: Kimura
authors.forename: Kyosuke
authors.initials: K
authors.lastname: Nagata
mesh_terms: D000818:Animals; D016466:CHO Cells; D002460:Cell Line; D006224:Cricetinae; D005818:Genetic Engineering; D006389:Hemagglutinins, Viral / Q000235:genetics / Q000378:metabolism*; D058507:Host Specificity; D006801:Humans; D008252:Macaca fascicularis; D008457:Measles / Q000378:metabolism / Q000821:virology*; D008458:Measles Vaccine / Q000235:genetics; D008459:Measles virus / Q000235:genetics / Q000502:physiology*; D051916:Membrane Cofactor Protein / Q000378:metabolism; D011485:Protein Binding; D056189:Viral Tropism; D014779:Virus Replication
chemical_list: D006389:Hemagglutinins, Viral; D008458:Measles Vaccine; D051916:Membrane Cofactor Protein