[Molecular and cellular bases for the effects of interferon]. / Molekuliarnye i kletochnye osnovy éffektov interferonov.

The data on the molecular mechanisms of interferons activity are analyzed. The analysis is based on the assumption that interferons are the substances of the hormonal nature. The initial step of the different interferons effects is attempted to be explained by the existence of the molecular and cellular reactions common for its realization. The dependence of the final results of interferons action on the metabolic processes in different cells and tissues determined by the specific functions and physiology of the latter is assumed.

[Transformation of mouse lymphocytes stimulated by phytohemagglutin depending on their cultivation conditions]. / Transformatsiia myshinykh limfotsitov, stumulirovannykh fitogemaggliutininom, v zavisimosti ot uslovii ikh kul'tivirovaniia.

Conditions were elaborated to cultivate splenocytes of mice in medium-199 (Soviet production) changed a little by the addition of 200 mM of glutamine, 6 mM glucose, 60 unit/l of insulin, 5.10(-5) M 2-mercaptoethanol (final concentration), and of 5% serum of new-born calf. In such conditions of cultivation the value of the lymphocyte transformation coefficient lies within 3 and 10.

[Effects of the antioxidant ionol on humoral immune response in experimental influenza]. / Vliianie antioksidanta ionola na gumoral'noe zveno immunogo otveta pri éksperimental'nom grippe.

The effect of the antioxidant ionol on a humoral immune response was studied in experimental influenza. With preventive introduction of ionol, the affinity of anti-influenza G antibodies circulating in the blood stream was shown to be decreased as compared to that in control animals. The changes in the affinity during influenza infection were cyclic and less marked in the group of animals receiving ionol. The administration of the antioxidant substantially reduced the detection rate of specific blood immune complexes and contributed to the production of antibody-forming cells. The findings suggest that ionol has a favourable effect on a humoral immune response in experimental influenza and alleviates the course of an infectious process.

[Stress and viral infection: dynamics of expression of influenza A viral antigens during immobilization stress]. / Stress i virusnaia infektsiia: dinamika ékspressii antigenov virusa grippa A pod deistviem immobilizatsionnogo stressa.

The level of expression of influenza virus antigens in the target organ is an important characteristic of the severity of a viral process, as was shown on a model of experimental influenza A. Stress exposure augmenting the severity of the infection stimulates the expression of viral polypeptides in the acute period of the disease. Injection of an antioxidant ionol which is effective in influenza may prevent stress-enhanced synthesis of viral proteins. Stress-induced disorder of the mechanisms of formation of immunological memory is paralleled by accumulation of high levels of virus-specific proteins in the lungs after repeated exposure of an animal to a homologous virus. Hence, the level of viral antigens synthesized in the course of reinfection also helps assess the degree of body protection from this agent.

[The effect of thymosine on the course of experimental influenza infection and antibody production in laboratory animals]. / Vliianie timozina na techenie éksperimental'noi grippoznoi infektsii i protsess antiteloobrazovaniia u laboratornykh zhivotnykh.

Thymosine is a preparation isolated from the thymus of calves. It possesses a specific activity stimulating maturation of T lymphocytes in splenocytes of thymectomized guinea pigs and peripheral blood of healthy humans. Thymosine had no effect on the course of severe experimental influenza infection and exerted no regular stimulation of antibody production in rats with asymptomatic influenza infection.

[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.

[Glucose utilization in influenza of varying severity in intact or stressed animals]. / Uvoenie gliukozy na fone grippoznoi infektsii raznoi tiazhesti u intaktnykh ili stressirovannykh zhivotnykh.

Animals preexposed to stress developed manifest hyperglycemia in the first 2 days of influenza infection, which was replaced by prolonged hypoglycemia. The status of carbohydrate metabolism normalized no sooner than 3 to 4 weeks after the disease onset, although the acute phase of infection was over by the end of week 2. The changes were evident in the pattern of "sugar curve" after glucose loading. Glucose utilization failed to normalize even 2 h after the loading in animals with stress, influenza infection, or stress-associated complications of this infection.

[Immunomodulating action of levamisole in influenzal infection in mice]. / Immunomoduliruiushchee deistvie levamizola pri grippoznoi infektsii myshei.

The time of the activation of the regulatory lymphocyte subpopulation in the spleen and the influence of levamisole on the course of influenza infection in mice were studied in parallel. The study revealed that the final effect of the immunomodulating action of levamisole was determined by the concrete phase of the regulatory activity of lymphocytes. At the same time the injection of the preparation at the peak of helper activity induced a transitory decrease in antibody formation and, in the fatal form of the infection, a rise in the death rate among the animals. The probable role of levamisole-activated macrophages in the transitory suppression of immune response in mice during influenza infection is discussed.

[Effectiveness of the combined use of an inactivated vaccine and a proteolysis inhibitor in the prevention of experimental influenza]. / Effktivnost' sochetannogo primeneniia inaktivirovannoi vaktsiny i ingibitora proteoliza v profilaktike éksperimental'nogo grippa.

The prophylactic effects produced by different types of antiviral preparations, used separately or in combination, in experimental lethal infection induced by influenza virus AO/32 (H0N1) in mice are compared. The use of inactivated vaccine and E-aminocaproic acid (E-ACA), a proteolysis-inhibiting agent, was studied. The qualitative characterization and quantitative evaluation of the anti-influenza effect were carried out by the method of multifactor analysis with the use of a computer after the optimum second-order plan based on the mathematical theory of experiment. This made it possible to determine the best combination of the preparations and their doses, to establish the time of the formation of reliable protection from influenza in mice. The prophylactic effect produced by the use of E-ACA alone and the capacity of this preparation for enhancing the protective action of inactivated influenza vaccine were established. Mathematical analysis revealed the optimum value of the four factors under study: the dose of the vaccine, the dose of E-ACA, the lapse of time between the injection of the preparations and the challenge of the animals, as well as the infective dose of the pathogenic virus. A special experiment made in the study of these data confirmed that the specific formation of a high level of anti-influenza protection in mice can be achieved by the combined use of the vaccine and the inhibitor of proteolysis.

[Dynamics of change in the antibacterial activity of mouse peritoneal cells during the development of experimental influenzal infection]. / Dinamika izmeneniia antibakterial'noi aktivnocti peritoneal'nykh kletok myshei pri razvitii éksperimental'noi grippoznoi infektsii.

The method of the radiometric determination of the antibacterial activity of peritoneal cells in the process of the development of viral infection has been approved. The genetically determined specific level of the antibacterial activity of these cells in different strains of mice has been established. The development of the lethal form of experimental influenza A in mice has been shown to be accompanied by the mobilization of nonspecific protective factors, including the system of interferons and the antibacterial activity of peritoneal cells. The latter factor is, seemingly, insufficient for ensuring the necessary level of protection in the animals, whose death occurs at a shorter time than that necessary for the development of specific immune response.

[Effect of immobilization stress on the course of experimental influenza infection and the process of interferon formation]. / Vliianie immobilizatsionnogo stressa na techenie éksperimental'noi grippoznoi infektsii i protsess interferonoobrazovaniia.

The experimental data on the peculiar features of interferon production in C57BL/6 mice, infected with the lethal dose of influenza virus and simultaneously subjected to the action of a stress factor, are presented. Immobilization stress was found to exert pronounced influence on the interferon-producing system of the body, which was manifested by the appearance of alpha interferon in a titer of up to 1:80 in the blood of intact animals. 6-hour immobilization preceding infection did not accelerate the development of the lethal from of influenza infection, but sharply suppressed the viral induction of the synthesis of interferon.

[The effect of mutation in the NS gene on the biological properties of the influenza virus]. / Vliianie mutatsii v gene NS na biologicheskie svoistva virusa grippa.

The biological properties of influenza virus strain A/PR/8/34, virulent from mice, and its variant 25A-1, obtained by hybridization with avirulent strain A/Leningrad. This reassortant 25A-1 included 7 genes of its virulent parent strain and only gene NS of the avirulent one, which contained a single mutation in position 798 (ATG=>ATA), inducing amino acid change MET=>IIe in position 100 of the polypeptide chain of protein NS2. The loss of pathogenic properties by strain A/PR/8/34 was achieved by replacing the single gene NS with an analogous mutant gene of the variant strain A/Leningrad, adapted to low temperatures. The single-gene reassortant 25A-1 thus obtained possessed, besides decreased capacity for multiplication in the lungs of mice, ts phenotype on MDCK cells, but exhibited no thermal sensitivity in cell systems of avian origin. The above-mentioned phenotypic changes in reassortant 25A-1 were due to disturbances in virus-specific protein synthesis at early and late stages, as detected in vivo and in vitro.

[The cellular link in the immune response in the dynamics of experimental infection caused by influenza A viruses with various properties]. / Kletochnoe zveno immunnogo otveta v dinamike éksperimental'noi infektsii, vyzvannoi virusami grippa A s raznymi svoistvami.

The development of the cell-mediated element of immunity in mice in the course of experimental influenza caused by the virulent and avirulent (ts-mutant) variants of influenza A virus was compared. The strains under test were also found to differ in their capacity for reproduction in pulmonary tissue, which could be determined for the mutant variant A/PR/8/59/1 (with 5 ts-mutations in genes P2, P3, NP, NA and M) only at an effective dose of 7.5 lg EID50. In mice infected with the initial and ts-variants of influenza A virus the formation of all mechanisms of the cell-mediated and humoral elements of immunity (natural killer activity, antitoxic T-lymphocyte activity, antibody-dependent cellular cytotoxicity, virus-specific antibodies) occurred. The curves showing the dynamics of the formation of cytotoxic mechanisms had a phasic (cyclic) character in all forms of the infectious process under study (lethal, sublethal and poorly reproductive). A dose-dependent effect on the character of the formation of these mechanisms was registered; besides, at the later period of observation (till day 14) the presence of activity was noted when the infectious virus was not detected, which may serve as an additional evidence of the prolonged expression of the viral genome in the body of the host.