title: The SI strain of measles virus derived from a patient with subacute sclerosing panencephalitis possesses typical genome alterations and unique amino acid changes that modulate receptor specificity and reduce membrane fusion activity.
abstract: Subacute sclerosing panencephalitis (SSPE) is a fatal sequela associated with measles and is caused by persistent infection of the brain with measles virus (MV). The SI strain was isolated in 1976 from a patient with SSPE and shows neurovirulence in animals. Genome nucleotide sequence analyses showed that the SI strain genome possesses typical genome alterations for SSPE-derived strains, namely, accumulated amino acid substitutions in the M protein and cytoplasmic tail truncation of the F protein. Through the establishment of an efficient reverse genetics system, a recombinant SI strain expressing a green fluorescent protein (rSI-AcGFP) was generated. The infection of various cell types with rSI-AcGFP was evaluated by fluorescence microscopy. rSI-AcGFP exhibited limited syncytium-forming activity and spread poorly in cells. Analyses using a recombinant MV possessing a chimeric genome between those of the SI strain and a wild-type MV strain indicated that the membrane-associated protein genes (M, F, and H) were responsible for the altered growth phenotype of the SI strain. Functional analyses of viral glycoproteins showed that the F protein of the SI strain exhibited reduced fusion activity because of an E300G substitution and that the H protein of the SI strain used CD46 efficiently but used the original MV receptors on immune and epithelial cells poorly because of L482F, S546G, and F555L substitutions. The data obtained in the present study provide a new platform for analyses of SSPE-derived strains as well as a clear example of an SSPE-derived strain that exhibits altered receptor specificity and limited fusion activity.
authors.affiliation: Department of Virology 3, National Institute of Infectious Diseases, Gakuen 4-7-1, Musashimurayama 208-0011, Tokyo, Japan. fseki@nih.go.jp
authors.forename: Fumio
authors.initials: F
authors.lastname: Seki
authors.forename: Kentaro
authors.initials: K
authors.lastname: Yamada
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Nakatsu
authors.forename: Koji
authors.initials: K
authors.lastname: Okamura
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Yanagi
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Nakayama
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Komase
authors.forename: Makoto
authors.initials: M
authors.lastname: Takeda
mesh_terms: D019943:Amino Acid Substitution; D004252:DNA Mutational Analysis; D016679:Genome, Viral; D006801:Humans; D008459:Measles virus / Q000235:genetics / Q000302:isolation & purification* / Q000472:pathogenicity*; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D012367:RNA, Viral / Q000235:genetics; D017422:Sequence Analysis, DNA; D013344:Subacute Sclerosing Panencephalitis / Q000821:virology*; D014764:Viral Proteins / Q000235:genetics; D056189:Viral Tropism; D014774:Virulence; D053586:Virus Internalization
chemical_list: D012367:RNA, Viral; D014764:Viral Proteins