Abstract
Live attenuated vaccine is used for vaccination. The temperature-sensitive (ts) phenotype is characteristic for almost all vaccinal rubella strains. The acquisition of the temperature-sensitive phenotype during adaptation to cold is strongly correlated with attenuation of the wild-type virus. Nevertheless, the molecular mechanisms of rubella virus attenuation have been insufficiently studied. Hence, it is still urgent to study the mechanisms of wild-type virus attenuation and search for key mutations leading to attenuation, as well as detect phenotypic signs that may serve as attenuation markers and be used, along with sequencing, for vaccinal strain genetic stability supervision. This study presents complete genome sequencing of the wild-type (wt) and cold-adapted (ca) C-77 rubella strain variants isolated in Russia; probable genetic determinants have been revealed. After comparison of the wt and ca genomes of the C-77 strain, 13 nucleotide differences were detected, of which six resulted in amino acid substitutions; four differences out of the six that result in these substitutions virtually do not occur in wild-type strains of the rubella virus. Tyr1042Cys substitution is of special interest in the protease domain of the C-77 strain, which likely plays a crucial role in cold-adapted phenotype acquisition by the C-77 strain.
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Original Russian Text © G.V. Dmitriev, T.K. Borisova, E.B. Faizuloev, Yu.I. Zabiyaka, R.G. Desyatskova, V.V. Zverev, 2012, published in Molekulyarnaya Genetika, Mikrobiologiya i Virusologiya, 2012, No. 3, pp. 28–33.
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Dmitriev, G.V., Borisova, T.K., Faizuloev, E.B. et al. A study of molecular mechanisms of rubella virus attenuation evidenced from the Russian C-77 strain. Mol. Genet. Microbiol. Virol. 27, 120–126 (2012). https://doi.org/10.3103/S0891416812030032
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DOI: https://doi.org/10.3103/S0891416812030032