title: Amino acid substitutions in the heptad repeat A and C regions of the F protein responsible for neurovirulence of measles virus Osaka-1 strain from a patient with subacute sclerosing panencephalitis.
abstract: Measles virus (MV) is the causative agent of subacute sclerosing panencephalitis (SSPE). We previously reported that the F gene of the SSPE Osaka-2 strain is the major determinant of MV neurovirulence. Because the sites and extents of mutations differ among SSPE strains, it is necessary to determine the mutations responsible for the SSPE-specific phenotypes of individual viral strain. In this study, recombinant viruses containing the envelope-associated genes from the SSPE Osaka-1 strain were generated in the IC323 wild-type MV background. Hamsters inoculated with MV containing the H gene of the Osaka-1 strain displayed hyperactivity and seizures, but usually recovered and survived. Hamsters inoculated with MV containing the F gene of the Osaka-1 strain displayed severe neurologic signs and died. Amino acid substitutions in the heptad repeat A and C regions of the F protein, including a methionine-to-valine substitution at amino acid 94, play major roles in neurovirulence.
authors.affiliation: Department of Virology, Graduate School of Medicine, Osaka City University, Osaka 545-8585, Japan. Electronic address: maverick@med.osaka-cu.ac.jp.
authors.forename: Minoru
authors.initials: M
authors.lastname: Ayata
authors.affiliation: Laboratory of Veterinary Pathology, Osaka Prefecture University, Osaka 598-8531, Japan.
authors.forename: Miyuu
authors.initials: M
authors.lastname: Tanaka
authors.affiliation: Department of Virology, Graduate School of Medicine, Osaka City University, Osaka 545-8585, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Kameoka
authors.affiliation: Laboratory of Veterinary Pathology, Osaka Prefecture University, Osaka 598-8531, Japan.
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Kuwamura
authors.affiliation: Laboratory of Environmental Microbiology, Division of Biomedical Science, Faculty of Medicine, University of Tsukuba, Ibaraki 305-8575, Japan.
authors.forename: Kaoru
authors.initials: K
authors.lastname: Takeuchi
authors.affiliation: Department of Virology 3, National Institute of Infectious Diseases, Tokyo 208-0011, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Takeda
authors.affiliation: Infectious Disease Surveillance Center, National Institute of Infectious Diseases, Tokyo 208-0011, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Kanou
authors.affiliation: Department of Virology, Graduate School of Medicine, Osaka City University, Osaka 545-8585, Japan.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Ogura
mesh_terms: D019943:Amino Acid Substitution / Q000235:genetics*; D000818:Animals; D001921:Brain / Q000821:virology; D016466:CHO Cells; D002144:Callithrix; D002460:Cell Line; D002522:Chlorocebus aethiops; D006224:Cricetinae; D003412:Cricetulus; D006801:Humans; D008459:Measles virus / Q000235:genetics* / Q000302:isolation & purification / Q000472:pathogenicity*; D017434:Protein Structure, Tertiary; D013344:Subacute Sclerosing Panencephalitis / Q000821:virology*; D014709:Vero Cells; D014760:Viral Fusion Proteins / Q000235:genetics*
chemical_list: D014760:Viral Fusion Proteins
keywords: Fusion; Hemagglutinin; Measles virus; Neurovirulence; Subacute sclerosing panencephalitis