title: Measles virus selectively blind to signaling lymphocytic activation molecule (SLAM; CD150) is attenuated and induces strong adaptive immune responses in rhesus monkeys.
abstract: The signaling lymphocytic activation molecule (SLAM; CD150) is the immune cell receptor for measles virus (MV). To assess the importance of the SLAM-MV interactions for virus spread and pathogenesis, we generated a wild-type IC-B MV selectively unable to recognize human SLAM (SLAM-blind). This virus differs from the fully virulent wild-type IC-B strain by a single arginine-to-alanine substitution at amino acid 533 of the attachment protein hemagglutinin and infects cells through SLAM about 40 times less efficiently than the isogenic wild-type strain. Ex vivo, this virus infects primary lymphocytes at low levels regardless of SLAM expression. When a group of six rhesus monkeys (Macaca mulatta) was inoculated intranasally with the SLAM-blind virus, no clinical symptoms were documented. Only one monkey had low-level viremia early after infection, whereas all the hosts in the control group had high viremia levels. Despite minimal, if any, viremia, all six hosts generated neutralizing antibody titers close to those of the control monkeys while MV-directed cellular immunity reached levels at least as high as in wild-type-infected monkeys. These findings prove formally that efficient SLAM recognition is necessary for MV virulence and pathogenesis. They also suggest that the selectively SLAM-blind wild-type MV can be developed into a vaccine vector.
authors.affiliation: Mayo Clinic, Department of Molecular Medicine, 200 First Street SW, Rochester, MN 55905, USA.
authors.forename: Vincent H J
authors.initials: VH
authors.lastname: Leonard
authors.forename: Gregory
authors.initials: G
authors.lastname: Hodge
authors.forename: Jorge
authors.initials: J
authors.lastname: Reyes-Del Valle
authors.forename: Michael B
authors.initials: MB
authors.lastname: McChesney
authors.forename: Roberto
authors.initials: R
authors.lastname: Cattaneo
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D015703:Antigens, CD / Q000502:physiology*; D002460:Cell Line; D006801:Humans; D008253:Macaca mulatta; D008458:Measles Vaccine / Q000276:immunology; D008459:Measles virus / Q000276:immunology / Q000472:pathogenicity / Q000502:physiology*; D051916:Membrane Cofactor Protein / Q000502:physiology; D011956:Receptors, Cell Surface / Q000502:physiology*; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D013601:T-Lymphocytes / Q000821:virology; D014764:Viral Proteins / Q000502:physiology; D053586:Virus Internalization
chemical_list: D015703:Antigens, CD; C497857:CD46 protein, human; D008458:Measles Vaccine; D051916:Membrane Cofactor Protein; D011956:Receptors, Cell Surface; C000604059:SLAMF1 protein, human; D014764:Viral Proteins; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1