[Role of individual genes in expression of phenotypic properties of the cold-adapted strain A/Leningrad/134/47/57 (H2N2)-a donor of attenuation of live influenza vaccine]. / Rol' otdel'nykh genov v proiavlenii fenotipicheskikh svoistv kholodoadaptirovannogo shtamma A/Leningrad/134/47/57 (H2N2)-- donora attenuatsii zhivykh grippoznykh vaktsin.

The influenza A/Leningrad/134/47/57 (H2N2) (A/Len/47) cold-adapted virus expresses the ability to reproduce at 25 degrees C (the ca phenotype) and inability to reproduce at 40 degrees C (the ts phenotype). It was attenuated for mice. Reassortants of this donor virus with the genes coding for the surface glycoproteins from the epidemic viruses, i.e. hemagglutinin (HA) and neuraminidase (NA), have been shown to be attenuated, immunogenic and genetically stable. We made attempts to reveal the influence of individual genes from the A/Len/47 ca virus on the expression of some phenotypic properties. Different "single-gene" reassortants were created and investigated using the influenza A/PR/8/34 (H1N1) virus as another parent with the opposite phenotypic properties, i.e. lack of ca+ and ts+ phenotypes and high virulence for mice. We managed to obtain "single-gene" reassortants with PB1, NA and NS genes at this stage of the work. None of them (probably including the M gene as well) could determine the ca or ts phenotypes, nor could the presence of the NA and NS genes from the strain A/Len/47 influence these properties. However, our findings show that the combined influence (synergism) of the PB1 and NS genes from the ca donors results in the ts phenotype of the reassortants. Significant role of the NS gene for attenuation of influenza viruses in mice has been revealed.

[Features of mutated changes of genomic RNA of cold-adapted and hr-variants of influenza group A virus, detected by RNA:RNA hybridization]. / Osobennosti mutatsionnykh izmenenii genomnoi RNK kholodoadaptirovannykh i hr-variantov virusa grippa A, vyiavliaemye metodom RNK:RNK-gibridizatsii.

The presence of mutations in the majority of the genes of cold-adapted strains A/Leningrad/134/17/57 (H2N2), A/Leningrad/134/47/57 (H2N2) and A/PR/8/59/1 (H1N1) of influenza A virus has been demonstrated by the RNA-RNA hybridization with the subsequent electrophoresis of double-stranded RNA in 7.5% polyacrylamide gel. The strains were cultivated 17, 47 and 59 passages in the chicken embryos at 25 degrees C. In the genomes of variants passaged in chicken embryos at optimal temperature of incubation 36 degrees C (hr-variants) the used technique permits identification of a single mutant gene. The obtained data suppose the attenuation of cold-adapted vaccine strains of influenza A virus and their high genetic stability to be a result of selection of the variants obtaining multiple mutations in the genome during passaging of the virions at cold temperature. The attenuation of hr-variants is defined by 1-2 mutations (first of all in HA-gene) that makes understandable their inability to serve as donors for recombinant live influenza vaccines construction.

[Genetic basis for construction of the life influenza type A vaccine using temperature-sensitive mutants]. / Geneticheskie osnovy konstruirovaniia zhivoi grippoznoi vaktsiny tipa A na osnove temperaturochuvstvitel'nykh mutantov.

Published data and authors' original material on the use of temperaturesensitive influenza virus mutants (ts) as donors in attenuation process aimed at obtaining the recombinant live influenza vaccines (LIV) are reviewed. The so called cold adapted ts donors are shown to be superior for this aim. The data are presented in the review on the association of the mutations in the genome of cold adapted donors with attenuation, on the reactivity, immunogenicity and genetical stability of the recombinant LIVs constructed on the basis of the cold adapted donors.