title: Contribution of matrix, fusion, hemagglutinin, and large protein genes of the CAM-70 measles virus vaccine strain to efficient growth in chicken embryonic fibroblasts.
abstract: Attenuated live vaccines of measles virus (MV) have been developed from clinical isolates by serial propagation in heterologous cells, mainly chicken embryonic cells. The safety and effectiveness of these vaccines have been well established. However, the molecular mechanism of their attenuation remains a subject of investigation. The CAM-70 MV vaccine strain was developed from the Tanabe strain by serial propagation in chicken embryonic cells. In the present study, we assessed the contribution of each gene in the CAM-70 strain to efficient growth in chicken embryonic fibroblasts (CEF). We used a cloned MV IC323 based on the wild-type IC-B strain and generated a series of IC323s that possess one or more of the CAM-70 genes. Then, we examined the infection of CEF and CEF expressing human signaling lymphocyte activation molecule with the recombinant MVs. Our results demonstrated that MV needs to adapt to CEF at both the entry and postentry steps and that the CAM-70 matrix protein gene plays an important role in adaptation to CEF at the early stage of the virus replication cycle. The CAM-70 large protein gene was responsible for the efficient transcription and replication in CEF, and the CAM-70 hemagglutinin and fusion protein genes were responsible for efficient entry. Investigations focusing on these genes might elucidate unknown molecular mechanisms underlying the attenuation of MV.
authors.affiliation: Department of Virology, Osaka City University Medical School, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan.
authors.forename: Luna Bhatta
authors.initials: LB
authors.lastname: Sharma
authors.forename: Shinji
authors.initials: S
authors.lastname: Ohgimoto
authors.forename: Seiichi
authors.initials: S
authors.lastname: Kato
authors.forename: Sekiko
authors.initials: S
authors.lastname: Kurazono
authors.forename: Minoru
authors.initials: M
authors.lastname: Ayata
authors.forename: Kaoru
authors.initials: K
authors.lastname: Takeuchi
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Ihara
authors.forename: Hisashi
authors.initials: H
authors.lastname: Ogura
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D002642:Chick Embryo / Q000821:virology; D003001:Cloning, Molecular; D004274:DNA, Recombinant / Q000235:genetics; D005347:Fibroblasts / Q000821:virology; D005434:Flow Cytometry; D005814:Genes, Viral / Q000502:physiology; D006389:Hemagglutinins, Viral / Q000235:genetics*; D006801:Humans; D008458:Measles Vaccine / Q000235:genetics*; D008459:Measles virus / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic / Q000235:genetics; D014161:Transduction, Genetic; D014763:Viral Matrix Proteins / Q000235:genetics; D014764:Viral Proteins / Q000235:genetics; D053586:Virus Internalization; D014779:Virus Replication / Q000235:genetics
chemical_list: D004274:DNA, Recombinant; D006389:Hemagglutinins, Viral; D008458:Measles Vaccine; D014763:Viral Matrix Proteins; D014764:Viral Proteins; C032397:hemagglutinin protein G, measles virus