Krutikova E V, Stepanova E A, Kiseleva I V, Rudenko L G
A. A. Smorodintsev Department of Virology, Institute of Experimental Medicine, St. Petersburg, Russia.
Bull Exp Biol Med. 2019 Jul;167(3):384-387. doi: 10.1007/s10517-019-04532-x. Epub 2019 Jul 26.
We studied the constellation of genes encoding polymerase complex proteins of master donor viruses for Russian live attenuated influenza vaccine type B. Reassortants of the reserve attenuation donor B/Leningrad/14/17/55 with B/USSR/60/69 master donor virus currently used for manufacturing seasonal influenza vaccine were prepared and examined. Most reassortants obtained by the classical reassortment method inherited all genes from the B/Leningrad/14/17/55 virus except the gene encoding PB1 subunit of the polymerase complex. One reassortant was selected for further evaluation of the role of PB1 gene. Greater attenuation of the strain for experimental animals (mice) in comparison with the original strains was demonstrated. This indicates high degree of constellation of genes of cold-adapted master donor viruses and the important compensating role of amino acid substitutions in the PB1 protein of B/Leningrad/14/17/55 donor virus in preventing viral hyperattenuation.
我们研究了俄罗斯B型减毒活流感疫苗主供体病毒编码聚合酶复合蛋白的基因组合。制备并检测了储备减毒供体B/列宁格勒/14/17/55与目前用于生产季节性流感疫苗的B/苏联/60/69主供体病毒的重配体。通过经典重配方法获得的大多数重配体除了聚合酶复合体PB1亚基编码基因外，均继承了B/列宁格勒/14/17/55病毒的所有基因。选择了一个重配体用于进一步评估PB1基因的作用。与原始毒株相比，该毒株对实验动物（小鼠）的减毒作用更强。这表明冷适应主供体病毒的基因组合程度很高，并且B/列宁格勒/14/17/55供体病毒PB1蛋白中的氨基酸取代在防止病毒过度减毒方面具有重要的补偿作用。
