[The influenza viruses and their surface proteins impact on the metabolism of human blood vessel endothelium cells].

The modern influenza virus subtypes H3N2, H5N1, and H1N1 reduced the metabolism of the endothelial cells within the range from 20% to 60% (compared with control). The degree of the activity of the dehydrogenase reduction depended on the dose of virus and time of virus reproduction. HA and NA also actively reduced the metabolism of the cells ranging from 5% to 60%, depending on the concentration of the proteins and time of their impact on cells. Neuraminidase was more active than hemagglutinin in the MTT test (at concentration 50 microg protein/ml).

[Ability of the influenza viruses and their envelope proteins to stimulates endothelial cells apoptosis in vitro].

The ability of the modern epidemic strains of influenza virus type A (subtypes H5N1, H3N2, H1N1pdm) and their surface proteins, hemagglutinin (HA) and neuraminidase to cause the activation of the cellular protein caspase-3 and stimulate the emergence of phosphatidylserine on the membrane of human endothelial cell line EAhy926 has been studied. It was questioned how the viruses and their surface proteins that were studied cause the activation of caspase-3 after 0.5 h of exposure that recorded immunogistotsitohimicheski. The test viruses and neuraminidase (concentration 10 µg/ml) led to the appearance of phosphatidylserine on the cell membrane in a time interval of 2-8 h from the beginning of the treatment, which was recorded by flow cytometry. The death of endothelial cells when exposed to the HA (in a concentration of 50 µg/ml) and in the same time frame was not accompanied by the appearance of phosphatidylserine. The specific feature of apoptotic cell death during the reproduction of the virus are described, as well as the effects of viral proteins.

[Influenza virus reproduction in the endothelial cells of human blood vessels].

The current epidemic strains of the influenza subtypes Y5N1, H3N2, and H1N1 can be reproduced in the cultured human endothelial EAhy926 cells with an infective activity of 3.0-4.5 Ig TCD50. These findings were confirmed by the analysis of the autopsy material from patients who had died from influenza during the 2009-2010 epidemic, which showed influenza virus HA and NP proteins in the pulmonary blood vascular endothelium. The results obtained reflect a new aspect of the pathogenesis of influenza, which is important for the design of antiviral agents and for the development of combination therapy.

[Pathogenic aspects of influenza during the epidemics caused by A/H1N1v virus in 2009-2010 according autopsy data].

The paper is based upon the results of clinic-pathological and virological correlations in 29 lethal cases of influenza in Saint-Petersburg and Leningrad region during the epidemics 2009/2010. Immunohistochemical analysis of lungs, heart and brain using monoclonal sera to HA and HP proteins of influenza virus, virological and morphological analysis of experimental influenza in mice infected by A/WSN/33 (HIN1) and A/California/07/09 (H1N1) viruses had been carried out. In the majority of investigated strains was proved the amino acid mutation with replacement D222G. The replication of virus was demonstrated at the late stages of diseases, but the desquamation of respiratory epithelium and cytoproliferative weren't found out. Besides the "influenza cells", previously described by A. V Zinserling the cells with enlarge light nuclei were observed. Patients with influenza died from respiratory distress syndrome with minimal bacterial infection. We've established that H1N1 virus not only damages the cells of respiratory epithelium and alveolar macrophages but it can injure endothelium of different organs and neuroglia. The questions which have to be discussed are listed.

[Influence of isolated virion proteins of hepatitis A virus on the behavior of rats]. / Vliianie izolirovannykh virionnykh belkov virusa grippa A na povedenie krys.

Influenza A virus M-proteins can cause depression in experimental animals 1 day after administration. HA and NA, on the contrary, activate motor activity in animals under the similar conditions. The effect of viral proteins is dose-dependent.

[Role of neuraminidase in pathogenesis of influenza]. / Rol' neiraminidazy v patogeneze grippozonoi infektsii.

The influenza neuraminidase (NA) possesses, both in vivo and in vitro, the anticoagulant and fibrinolytic activity. A computerized comparative analysis of the influenza NA viruses, type A, showed nine regions of amino-acid sequences compatible with the tissue activator of human plasminogen. The mentioned regions are highly conservative for each NA subtype irrespective of a source or a year, when an influenza strain was isolated. The role of NA in pathogenesis of influenza infection is under consideration.

[ Influenza virus proteins modulate hemostasis in vitro and in vivo ]. / Belki virusa grippa moduliruiut gemostaz in vitro i in vivo.

We studied the effect of influenza virus proteins--hemagglutinin, neuraminidase, nucleoprotein, and membrane protein--on hemostasis in vitro and in vivo. The obtained data demonstrated that the envelope proteins hemagglutinin and neuraminidase increased the plasma fibrinolytic and anticoagulant activities and the activity of human tissue plasminogen activator. Among the core proteins of influenza virus, membrane protein proved to have the highest activity; in contrast to hemagglutinin and neuraminidase, it inhibited fibrinolysis, increased the coagulation activity of the plasma, and decreased the activity of human tissue plasminogen activator. Combined action of hemagglutinin and neuraminidase increased the plasma fibrinolytic and anticoagulant activities exceeding their individual effects. Combined action of an envelope protein hemagglutinin and membrane protein also increased the plasma fibrinolytic and anticoagulant activities although to a lesser extent as compared to hemagglutinin alone. The obtained data indicate that the viral proteins are physiologically active and can induce hemostatic changes specific for influenza.

[The effect of influenza virus hemagglutinin on erythrocytes and thrombocytes]. / Vliianie gemaggliutinina virusa grippa na éritrotsity i trombotsity.

We studied the effect of influenza virus hemagglutinin on the volume of erythrocytes and aggregation activity of thrombocytes. Hemagglutinin proved to increase the erythrocyte volume, which ends in their lysis, and to induce disaggregation of the thrombocytes. The effect of hemagglutinin on the erythrocytes and thrombocytes was dose-dependent.

[The role of influenza virus hemagglutinin in blood anticoagulation processes]. / Uchastie gemaggliutinina virusa grippa v protsessakh antikoaguliatsii krovi.

Influenza virus hemagglutinin (HA) possesses anticoagulant and fubrinolytic activities and affects such blood clotting factors as fibrinogen and factor XIII in vitro and in vivo. Computer analysis of HA structure of avian, animal, and human type 1 influenza viruses showed 1 or 2 sites of amino acid sequences similar to plasminogen activator. These sites proved to be highly conservative for each virus subtype, irrespective of the source and year of isolation of the strain. Evolution relationships with respect to this sign were detected between the studied viruses.

[Effects of influenza virus proteins on immunocompetent cells of the host]. / Vozdeistvie belkov virusa grippa na immunokompetentnye kletki organizma khoziaina.

Only 2 influenza viral proteins--HA and M--have been shown to be active against host T cells, M protein being more active than HA in some tests when interacted with CD4 receptor. M protein stimulated the expression of CD25 receptors and the proliferation of lymphocytes; the activated production of alpha-tumor necrosis factor was undetectable when exposed to virus proteins.

[Detection in the structure of influenza viral proteins of sequences similar to vasoactive intestinal peptide]. / Vyiavlenie v strukture belkov virusa grippa posledovatel'nostei, skhodnyk s vazoaktivnym intestinal'nym peptidom.

The paper presents the results on the influenza virus proteins (only HA, M and NS) contained in the amino acid sequence regions similar to that of the VIP. These data may be important as there is similarity in pathological reactions between VIP and influenza virus.

[Isolation and comparative study of highly reproductive recombinant influenza A viruses with a high antibody sensitivity]. / Poluchenie i sravnitel'noe izuchenie vysokoreproduktivnykh rekombinantov virusa grippa A s vysokoi chuvstvitel'nost'iu k antitelam.

The possibility of generating avid and highly reproductive recombinants of influenza A virus (H3N2, H3N1) using strain A/PR/8/34 (H1N1) as a donor of high reproductive activity was demonstrated. In the process of recombination, the transmission of the gene responsible for synthesis of avid hemagglutinin H3 from one virus variant to another provides for high avidity of recombinants. However, a possible influence of other influenza A virus genes on the manifestation of avidity cannot be ruled out.

[Study of influenza virus hemagglutinin H3 avidity using monoclonal antibodies]. / Izuchenie avidnosti gemaggliutinina H3 virusa grippa s pomoshch'iu monoklonal'nykh antitel.

The results of a comparative study of the features of antigenic determinants of avid and non-avid variants of influenza virus hemagglutinin H3 and of the influence of the mode of antigen presentation on the degree of its avidity are presented. The avidity of influenza virus hemagglutinin was shown to be determined by the capacity of individual antigenic determinants to interaction with antibodies. The antigenic determinants of avid hemagglutinin possessing a high functional activity in interaction with antibodies may have the spatial configuration which does not change in different modes of the antigen presentation. Isolation of hemagglutinin from virions of non-avid virus variants may lead to increased functional activity of individual antigenic determinants (and the antigen molecule as a whole) probably due to an increased degree of exposure and/or complementarity of the determinants for active centres of antibody.

[Structure of the hemagglutinin gene of the influenza virus during serial passages in chick embryos]. / Struktura gena gemaggliutinina virusa grippa pri seriinykh passazhakhna kurinykh émbrionakh.

The sequence analysis of HA gene of passaged variants of A/USSR/2/85 influenza virus was carried out. It was shown that in the process of passage of virus in chick embryos the structure of HA gene was not changed. These data correlated with those obtained early during investigation of A/Leningrad/337/76 influenza virus by the oligonucleotide mapping.