title: [Studying of molecular mechanisms of rubella virus attenuation evidence from Russian strain C-77].
abstract: Live attenuated rubella vaccine is used for vaccination. Temperature-sensitive (ts) phenotype was proved for almost all rubella vaccine strains, and the acquisition of the ts phenotype during cold adaptation was strongly correlated with the attenuation of the wild-type viruses. Nevertheless, the molecular mechanisms of the attenuation have been insufficiently understood for rubella virus. Study ofthese mechanisms, identifying genotypic markers of attenuation, which together with the sequence analyses could be used for genetic stability control of vaccine strains, is still of current interest. In this work, we determined nearly complete genome sequences of attenuated (ca) and the wildtype progenitor (wt) of the rubella virus strain C-77 isolated in Russia. Possible genetic determinants of attenuation were detected. Thus, 13 nucleotide differences leading to 6 amino acid substitutions were found. Four amino acid substitutions were found to be almost unique. Special consideration should be given to Tyr1042Cys substitution in the protease domain of C-77 strain, because it most probably plays the crucial role in acquisition of ts-phenotype.
authors.forename: G V
authors.initials: GV
authors.lastname: Dmitriev
authors.forename: T K
authors.initials: TK
authors.lastname: Borisova
authors.forename: E B
authors.initials: EB
authors.lastname: Faĭzuloev
authors.forename: Iu I
authors.initials: IuI
authors.lastname: Zabiiaka
authors.forename: R G
authors.initials: RG
authors.lastname: Desiatskova
authors.forename: V V
authors.initials: VV
authors.lastname: Zverev
mesh_terms: D000222:Adaptation, Physiological / Q000235:genetics; D019943:Amino Acid Substitution / Q000235:genetics; D000818:Animals; D002522:Chlorocebus aethiops; D003080:Cold Temperature; D016679:Genome, Viral; D006801:Humans; D010641:Phenotype; D010802:Phylogeny; D012409:Rubella / Q000235:genetics / Q000821:virology; D012411:Rubella Vaccine / Q000235:genetics; D012412:Rubella virus / Q000235:genetics / Q000472:pathogenicity; D012426:Russia; D017422:Sequence Analysis, DNA; D013696:Temperature; D014613:Vaccines, Attenuated / Q000235:genetics*; D014709:Vero Cells
chemical_list: D012411:Rubella Vaccine; D014613:Vaccines, Attenuated