[The NS gene--a possible determinant of apathogenicity of a cold-adapted donor of attenuation A /Leningrad/134/47/57 and its reassortants]. / Gen NS--veroiatnaia determinant apatogennosti kholodoadaptirovannogo donora attenuatsii A /Leningrad/134/47/57 i ego reassortantov.

Phenotypical properties of single-gene reassortants of attenuated cold-adapted strain A/Leningrad/135/47/57 (H2N2) and strain A/PR8/34 virulent for laboratory animals were studied. Only the group of reassortants inheriting NS gene from cold-adapted virus was fully attenuated for various animals species, similarly as reassortants with 6/2 genomic formula containing all the 6 internal protein genes from strain A/Leningrad/134/47/57. Reassortant 25A-1 single-gene for NS was temperature-sensitive (ts) on mammalian cells but formed plaques at 40 degrees C on chicken kidney cells. Reassortants with genomic formula 6/2 were temperature-sensitive in all types of cells used. Reassortant 25A-1 could synthesize normal amounts of polypeptides in MDCK cells at 39 degrees C, whereas protein synthesis of reassortants with 6/2 genomic formula was noticeably reduced at this temperature. Hence, a similar level of attenuation of both reassortant groups appears to be due to various molecular mechanisms. Possible role of NS2 gene mutation in attenuation of strain A/Leningrad/134/47/57 and its reassortants is discussed.

[Immunogenicity of attenuated reassortants of influenza A virus /Leningrad/134/47/57 (H2N2) for mice, depending on their genome]. / Immunogennost' dlia myshei attenuirovannykh reassortantov virusa grippa A /Leningrad/134/47/57 (H2N2) v zavisimosti ot sostava ikh genoma.

Reassortants of cold-adapted strain A/Leningrad/134/47/57 (H2N2) and virulent strain A/PR/8/34 (H1N1), modeling genomic composition of vaccinal strains, were tried in mouse experiments. Reassortants' genomes included the major part (5, 6, or 7) from cold-adapted strain and 1 to 3 genes of virulent strain. All the tested reassortants did not differ by temperature sensitivity or cold adaptation phenotypes, did not cause the death of mice, but differed by the level of reproduction in murine lungs and by immunogenicity. Strains with genomic formulas 6/2 (HA and NA of a virulent strain) and 5/3 (M) (HA, NA, and M of a virulent strain) were characterized by the highest immunogenicity. Reassortants including, besides HA and NA, PA gene 5/3 (PA) or inheriting only HA gene from strain A/pr/8/34 (H1N1) were hyperattenuated and low immunogenic.

[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.

[The evaluation of the degree of attenuation of cold-adapted influenza A virus strains in CBA-strain mouse and Syrian hamster models]. / Otsenka stepeni attenuatsii kholodo-adaptirovannykh shtammov virusa grippa A na modeliakh myshei linii CBA i siriiskikh khomiachkov.

The pattern of the infectious process induced by the epidemic A/Leningrad/134/57 (H2N2) virus and its cold-adapted (CA) variants in CBA mice and Syrian hamsters was studied. The strains under study inoculated into the animals under a mild ether anesthesia differed by virulence, reproductive capacity in the nasopharynx, trachea and lungs, as well as by the isolation rate from extrarespiratory organs of both mice and hamsters. Upon intranasal inoculation of mice without anesthesia, the CA strains were found to be incapable of dissemination into the lower parts of the respiratory tract with distinguished these viruses from the original epidemic strain A/Leningrad/134/57 as well as from the mouse-adapted strain A/PR/8/34 (H1N1) used as control. The experimental results show that both models are suitable for laboratory evaluation of the attenuation degree of human influenza viruses.

[The effect of amplifying reproduction of influenza virus in mouse lungs during simultaneous infection with two cold-adapted strains]. / Effekt usileniia reproduktsii virusa grippa v legkikh myshei pri odnobremennom infitsirovanii dvumia kholodoadaptirovannymi shtammami.

Reproduction of cold-adapted (ca) strains of influenza virus in the lungs of white mice after separate and combined inoculation and the properties of isolates derived from the infected animals were studied. It was shown that after combined inoculation with ca and ts strains A/Leningrad/134/17/57 (H2N2) and A/PR/8/59/1 (H1N1) ca recombinants could develop loosing some ts mutations and possessing (unlike the master strains) pneumo-virulence for mice. All the pneumo-virulent reassortants inherited hemagglutinin from the ca A/PR/8/59/1 strain and PB1 protein from the ca A/Leningrad/134/17/57 strain. The results indicate that it is unsafe to construct live recombinant divaccines by combining the recombinants produced from different donors of attenuation.

[Biological characteristics of epidemic and interepidemic strains of the influenza A (H3N2) virus]. / Biologicheskie osobennosti épidemicheskikh i mezhépidemicheskikh shtammov virusa grippa A (H3N2).

Comparative studies of biological properties of influenza A (H3N2) viruses isolated in the epidemics of 1980 and 1983 and in the interepidemic period of 1982 showed a sharp reduction of the biological activity of the interepidemic viruses as compared with that of the epidemic ones. This was manifested by low isolation rate of virus in the interepidemic period, reduced hemagglutinating, interfering, and immunogenic activity of these viruses, poor reproduction in the lung tissue of white mice and the lack of virus-specific syntheses in splenocytes of infected Syrian hamsters. Unlike epidemic strains, the interepidemic strains had ts mutation in gene 6 coding for neuraminidase. There are reasons to associate the observed defect in gene 6 with frequent development of asymptomatic forms of influenza infection in the interepidemic period.

[Reproduction of the vesicular stomatitis virus in mouse splenocytes]. / Reproduktsiia virusa vezikuliarnogo stomatita v splenotsitakh myshei.

Interaction of vesicular stomatitis virus with immunocompetent cells in vivo and in vitro was studied. In intact mice, a prolonged infection of the spleens with low levels of virus replication was observed. Experiments with various splenocyte cultures demonstrated differences in their capacity to support virus reproduction. A relationship between the functional activity of the cells (the level of spontaneous blastogenesis, index of PHA response) and levels of virus reproduction was shown. Mitogen stimulation of blastogenesis was accompanied by intensified replication in reactive cultures. In splenocyte cultures from immune animals, reproduction levels were decreased and virus replication stopped.

[Characteristics of the causative agents of the influenza A (H3N2) epidemic in Leningrad in 1983]. / Osobennosti vozbuditelei épidemii grippa A (H3N2) v Leningrade v 1982 g.

Investigation of influenza A (H3N2) epidemic of 1983 in Leningrad revealed simultaneous circulation of 3 antigenic variants similar to A/Bangkok/1/79, A/Bangkok/2/79, and A/Philippines/2/82 with significant predominance of the first antigenic variant. The viruses related to A/Philippines/2/82 comprising one-third of all isolations produced antibodies of a wide spectrum unlike the other two variants whose antisera neutralize actively the homologous virus only. The possibility of selecting epidemic strains of the A/Philippines/2/82 variety as vaccine strain candidates is discussed.

[Etiological characteristics of influenzal diseases in children's collectives under long-term observation]. / Osobennosti étiologii grippoznykh zabolevanii v dlitel'no nabliudaemykh detskikh kollektivakh.

As the result of epidemiological and virological observations, the factors which determined the duration of carriership at the period of mixed influenza A and B epidemic were established. Most children released influenza virus A for 7-9 days and influenza B virus for 10-12 days. The duration of carriership in children depended on their age, the level of humoral antibodies in their sera taken before the disease and the manifestation of their immune reaction to influenza virus infection.

[Antigenic and biological characteristics of influenza A1 viruses isolated in the 1977 pandemic]. / Antigennaia i biologicheskaia kharakteristika virusov grippa A1, izolirovannykh v pandemiiu 1977 g.

Investigations of the antigenic and biological properties of the causative agents of the 1977 influenza epidemic revealed their appurtenance to the old subtype A1 of influenza virus which had disappeared from circulation 20 years ago. A comparative study of A1 viruses isolated in 1947--1956 and A1/77 established closer relationship of the latter to the causative agents of 1949 and 1950 epidemics. The "old" and newly isolated viruses 4ere also closely related biologically. The similarity of influenza A1/77 viruses with the agents of the pandemic cycle of A1 in 1947--1956 is a convincing confirmation of the hypothesis of Francis-Davenport and Smorodintsev-Luzyanina.