Research Institute of Influenza

Saint Petersburg, Russia

Research Institute of Influenza

Saint Petersburg, Russia
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Weiss R.,Medical University of Vienna | Laengle J.,Medical University of Vienna | Sachet M.,Medical University of Vienna | Shurygina A.-P.,Research Institute of Influenza | And 3 more authors.
Antiviral Research | Year: 2015

New anti-viral agents and strategies are urgently needed to fight rapidly mutating viruses, as vaccine programs cannot react fast enough to prevent pandemics. Recently, we have shown that interleukin-24 (IL-24) sensitizes tumor cells to toll-like receptor 3 (TLR3) mediated apoptosis. As influenza A virus stimulates the TLR3 receptor, we hypothesized that IL-24 might also exert an anti-viral effect. This study demonstrates that IL-24 reduces the titer of different influenza A virus subtypes independently of type I interferon in an apoptosis dependent manner. The anti-viral effect of IL-24 correlated with caspase-3 activation and could be blocked by a pan-caspase inhibitor and by small interfering RNA (siRNA) directed towards TLR3. Surprisingly, caspase-3 activation in influenza A virus/IL-24-stimulated cells correlated with the down-regulation of the B-cell lymphoma 2 (Bcl-2) family member myeloid cell leukemia 1 (Mcl-1). Correspondingly, knockdown of Mcl-1 by siRNA enhanced caspase activation in influenza A virus infected cells and was furthermore linked to a reduction of viral titers. We conclude that IL-24 exerts an anti-viral role selectively purging virally infected cells by leading to a down-regulation of Mcl-1. Our findings might therefore represent the first step towards a new rational concept in the development of anti-viral strategies based on the induction of apoptosis. © 2015 Elsevier B.V. All rights reserved.


Konshina O.S.,Research Institute of Influenza Ministry of Health of the Russian Federation | Sominina A.A.,Research Institute of Influenza | Smorodintseva E.A.,Research Institute of Influenza | Stolyarov K.A.,Research Institute of Influenza Ministry of Health of the Russian Federation | Nikonorov I.Yu.,Research Institute of Influenza
Russian Journal of Infection and Immunity | Year: 2017

Analysis of changes in the population immunity level in adults for more than 20 Russian cities, collaborating with the Federal Center for Influenza, to circulating influenza viruses A(H1N1)pdm09, A(H3N2) and B in the period from 2009 to 2015 performed. By the beginning of the pandemic (October 2009) the population of Russia was almost se- ronegative to influenza A(H1N1)pdm09 virus. After the pandemia first wave mean geometric titers (GMT)s of antibodies to the pandemic virus increased by 2.6 times, after the second one by 4.9 times in comparison with initial GMT (1:5.5). A consistent increase in GMTs antibody after each of the subsequent seasons of active circulation of pandemic virus was observed reaching the maximum (1:41) by April 2013, after the next epidemic caused by this virus. The proportion of people with protective antibody titers in October 2009 to already started circulating influenza A(H1N1)pdm09 virus was 8.2%, to influenza A(H3N2) virus -58.3%, and influenza B virus -59.7%. Level of population immunity in adults to seasonal influenza A(H3N2) and B viruses throughout the observed period was significantly higher than to influenza virus A(H1N1)pdm09. The percentage of persons with protective antibody titers during the observed period varied for virus A(H3N2) in the range from 58.3 to 75.5%, for influenza B virus -from 59.7 to 82.3%. Accordingly, incidence rate for ILI and ARI in adult groups the population during influenza epidemic caused by these pathogens was lower than in the epidemics, associated with active circulation of influenza A(H1N1)pdm09 virus. The data obtained can be used in influenza forecasting for the upcoming season regarding the etiology and the expected epidemic intensity need for the relevant preventing measures development to decrease the burden from influenza.


Eropkin M.Yu.,Research Institute of Influenza | Melenevskaya E.Yu.,RAS Institute of Macromolecular Compounds | Nasonova K.V.,RAS Institute of Macromolecular Compounds | Bryazzhikova T.S.,Research Institute of Influenza | And 3 more authors.
Pharmaceutical Chemistry Journal | Year: 2013

Polyhydroxyfullerenes, fullerenols with various contents of hydroxy groups, C60(OH)12 - 14, C60(OH)18 - 24, and C60(OH)30 - 38, were synthesized. The first group was insoluble in water and exhibited no biological activity when introduced into cell cultures as suspensions. The other two versions of fullerenols possessed a broad spectrum of antiviral activity in vitro against actual strains of human influenza virus A(H1N1) and A(H3N2), avian influenza A(H5N1), human herpes simplex virus, adenovirus, and respiratory-syncytial virus. The water-soluble versions of fullerenol were non-toxic in vitro toward human and animal cells of various tissue origins. Besides the antiviral activity, the fullerenols demonstrated a protective effect against UVA-induced phototoxicity. The fullerenol version C60(OH)18 - 24 had the maximum biological activity for all studied parameters. The soluble biologically active versions of fullerenol could find application in pharmacology because they could serve as a basis for new effective and non-toxic antiviral and cytoprotective drugs. © 2013 Springer Science+Business Media New York.


Petukhova N.V.,Moscow State University | Gasanova T.V.,Moscow State University | Stepanova L.A.,Research Institute of Influenza | Rusova O.A.,Research Institute of Influenza | And 7 more authors.
Current Pharmaceutical Design | Year: 2013

A new approach for super-expression of the influenza virus epitope M2e in plants has been developed on the basis of a recombinant Tobacco mosaic virus (TMV, strain U1) genome designed for Agrobacterium-mediated delivery into the plant cell nucleus. The TMV coat protein (CP) served as a carrier and three versions of the M2e sequence were inserted into the surface loop between amino acid residues 155 and 156. Cysteine residues in the heterologous peptide were thought likely to impede efficient assembly of chimeric particles. Therefore, viral vectors TMV-M2e-ala and TMV-M2e-ser were constructed in which cysteinecodons 17 and 19 of the M2e epitope were substituted by codons for serine or alanine. Agroinfiltration experiments proved that the chimeric viruses were capable of systemically infecting Nicotiana benthamiana plants. Antisera raised against TMV-M2e-ala virions appear to contain far more antibodies specific to influenza virus M2e than those specific to TMV carrier particle (ratio 5:1). Immunogold electron microscopy showed that the 2-epitopes were uniformly distributed and tightly packed on the surface of the chimeric TMV virions. Apparently, the majority of the TMV CP-specific epitopes in the chimeric TMV-M2e particles are hidden from the immune system by the M2e epitopes exposed on the particle surface. The profile of IgG subclasses after immunization of mice with TMV-M2e-ser and TMV-M2e-ala was evaluated. Immunization with TMV-M2e-ala induced a significant difference between the levels of IgG1 and IgG2a (IgG1/IgG2a=3.2). Mice immunized with the chimeric viruses were resistant to five lethal doses (LD50) of the homologous influenza virus strain, A/PR/8/34 (H1N1) and TMV-M2e-ala also gave partial protection (5LD50, 70% of survival rate) against a heterologous strain influenza A/California/04/2009 (H1N1) (4 amino acid changes in M2e). These results indicate that a new generation candidate universal nanovaccine against influenza based on a recombinant TMV construct has been obtained. © 2013 Bentham Science Publishers.


Smirnov V.S.,ZAO CytoNIR | Zarubaev V.V.,Research Institute of Influenza | Anfimov P.M.,Research Institute of Influenza | Shtro A.A.,Research Institute of Influenza
Voprosy Virusologii | Year: 2012

The purpose of the study was to evaluate the modulating effect of glutamyl-tryptophan (EW), glycyrrhizic acid (GA), and their combination on the course of experimental infection caused by influenza A (H3N2) virus in mice. The animals were infected with influenza A/Aichi/2/68 (H3N2) virus in a dose of 1 or 10 LD50. GA (10 mg/kg body weight) and EW (0.1, 10, and 1000 μg/kg) alone or in combination were intraperitoneally injected for 5 days, starting on day 1 of virus infection. Rimantadine 50 mg/kg/day was used as a comparison drug. The combination of EW (1000 μg/kg) and GA (10 mg/kg) was ascertained to exert the maximum protective effect manifesting itself in reducing the death of infected animals (by 75-79% compared to the control depending on the viral dose) and the titers of viruses accumulated in the lung (5-6 log EID50) and in preventing lung tissue edema and inflammation. The noted effect was comparable with that seen in the use of rimantadine. The agents used alone had a lower efficacy than rimantadine. The findings permit the combination of GA and EW to be considered to be a promising agent for the treatment of influenza.


Mirgorodskaya O.A.,Research Institute of Influenza | Korner R.,Max Planck Institute of Biochemistry | Kozmin Y.P.,RAS Shemyakin Ovchinnikov Institute of Bioorganic Chemistry | Roepstorff P.,University of Southern Denmark
Methods in Molecular Biology | Year: 2012

Amino acid analysis is among the most accurate methods for absolute quantification of proteins and peptides. Here, we combine acid hydrolysis with the addition of isotopically labeled standard amino acids and analysis by mass spectrometry for accurate and sensitive protein quantitation. Quantitation of less than 10 fmol of protein standards with errors below 10% has been demonstrated using this method (1).


Vasin A.V.,Research Institute of Influenza | Temkina O.A.,Research Institute of Influenza | Egorov V.V.,Research Institute of Influenza | Klotchenko S.A.,Research Institute of Influenza | And 2 more authors.
Virus Research | Year: 2014

Influenza A virus is one of the major human pathogens. Despite numerous efforts to produce absolutely effective anti-influenza drugs or vaccines, no such agent has been developed yet. One of the main reasons for this complication is the high mutation rate and the specific structure of influenza A viruses genome. For more than 25 years since the first mapping of the viral genome, it was believed that its 8 genome segments encode 10 proteins. However, the proteome of influenza A viruses has turned out to be much more complex than previously thought. In 2001, the first accessory protein, PB1-F2, translated from the alternative open reading frame, was discovered. Subsequently, six more proteins, PB1-N40, PA-X, PA-N155, PA-N182, M42, and NS3, have been found. It is important to pay close attention to these novel proteins in order to evaluate their role in the pathogenesis of influenza, especially in the case of outbreaks of human infections with new avian viruses, such as H5N1 or H7N9. In this review we summarize the data on the molecular mechanisms used by influenza A viruses to expand their proteome and on the possible functions of the recently discovered viral proteins. © 2014 Elsevier B.V.


Koel B.F.,Erasmus University Rotterdam | Burke D.F.,University of Cambridge | Bestebroer T.M.,Erasmus University Rotterdam | Van Der Vliet S.,Erasmus University Rotterdam | And 17 more authors.
Science | Year: 2013

The molecular basis of antigenic drift was determined for the hemagglutinin (HA) of human influenza A/H3N2 virus. From 1968 to 2003, antigenic change was caused mainly by single amino acid substitutions, which occurred at only seven positions in HA immediately adjacent to the receptor binding site. Most of these substitutions were involved in antigenic change more than once. Equivalent positions were responsible for the recent antigenic changes of influenza B and A/H1N1 viruses. Substitution of a single amino acid at one of these positions substantially changed the virus-specific antibody response in infected ferrets. These findings have potentially far-reaching consequences for understanding the evolutionary mechanisms that govern influenza viruses.


Plotnikova M.A.,Research Institute of Influenza | Klotchenko S.A.,Research Institute of Influenza | Vasin A.V.,Polytechnic University of Mozambique
Journal of Immunological Methods | Year: 2016

Cytokines are global mediators of cellular communications that are involved in broad array of biological processes, including the immunological and inflammatory mechanisms of virus-host interactions. Measuring the gene expression of simultaneously expressed cytokines is necessary for understanding the pathogenesis of many viral infections, including influenza. We developed a multiplex quantitative real-time PCR (qPCR) method for the detection of the following human cytokines: IL-1B, IL-2, IL-4, IL-6, IL-10, IL-12B, IL-18, IFN-γ and TNF. The assay consisted of three sets of multiple qPCRs; in each qPCR, three target cytokines and reference GAPDH genes were amplified. The assay provided a precise and sensitive quantification of cytokine gene expression with a 20 fmol limit of detection and a 1.5% coefficient of variation. This method was successfully applied to cytokine profiling in epithelial A549 cells that were infected with A/California/07/09 (H1N1pdm2009) virus. © 2016 Elsevier B.V..


PubMed | Research Institute of Influenza and Tyva Republic Regional office of Federal Service for Surveillance on Consumer Rights Protection and Human Wellbeing Rospotrebnadzor
Type: | Journal: Archives of virology | Year: 2017

In the spring of 2016, a loss of wild birds was observed during the monitoring of avian influenza virus activity in the Republic of Tyva. That outbreak was caused by influenza H5N8 virus of clade 2.3.4.4. In the fall, viruses of H5N8 clade 2.3.4.4 were propagated in European countries. This paper presents some results of analysis of the virus strains isolated during the spring and fall seasons in 2016 in the Russian Federation. The investigated strains were highly pathogenic for mice, and some of their antigenic and genetic features differed from those of an H5N8 strain that circulated in 2014 in Russia.

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