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1
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A universal flu vaccine

100%
Kesik-Brodacka M., Plucienniczak G.
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2014
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vol. 61
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issue 3
523-530
EN
Influenza is a global health concern. The single most effective way of protecting people against influenza infection and disease is vaccination. However, currently available vaccines against influenza induce only strain-specific immunity, and do not elicit long-lasting serum antibody titers. Therefore, they are ineffective in the case of possible pandemics. There is an urgent need for a new generation vaccine which would induce broad and long-lasting immune protection against antigenically distinct flu viruses. The paper presents recent achievements and the challenges in the field of universal vaccine construction.
2
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Mapping of the influenza A hemagglutinin serotypes evolution by the ISSCOR method

88%
Radomski J., Słonimski P., Zagórski-Ostoja W., Borowicz P.
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2014
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vol. 61
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issue 3
441-451
EN
Analyses and visualizations by the ISSCOR method of influenza virus hemagglutinin genes of different A-subtypes revealed some rather striking temporal relationships between groups of individual gene subsets. Based on these findings we consider application of the ISSCOR-PCA method for analyses of large sets of homologous genes to be a worthwhile addition to a toolbox of genomics - allowing for a rapid diagnostics of trends, and ultimately even aiding an early warning of newly emerging epidemiological threats.
3
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Structural biology of the influenza virus fusion peptide

88%
Worch R.
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2014
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vol. 61
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issue 3
421-426
EN
The release of influenza RNA inside the host cell occurs through the fusion of two membranes, the viral envelope and that of the cellular endosome. The fusion is mediated by the influenza hemagglutinin protein (HA), in particular by the fusion peptide (HAfp) located in the N-terminal fragment of HA2 subunit. This protein fragment anchors in the internal endosomal membrane, whereas the C-terminal HA2 part comprises a transmembrane domain (TMD) embedded in the viral envelope. A drop of pH in the endosome acts as the main trigger for HA2 large conformational change that leads to anchoring of the fusion peptide, close contact of the membranes and the subsequent fusion. Throughout the years the major research effort was focused on a 20-aminoacid fragment (HAfp1-20), shown by NMR to adopt a 'boomerang'-like structure. However, recent studies showed that extending HAfp1-20 by three highly conserved residues W21-Y22-G23 leads to formation of a unique, tight helical hairpin structure. This review summarizes recently discovered structural aspects of influenza fusion peptides and their relations with the membrane fusion mechanism.
4
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Antiviral activity of novel oseltamivir derivatives against some influenza virus strains

88%
Kocik J., Kołodziej M., Joniec J., Kwiatek M., Bartoszcze M.
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2014
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vol. 61
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issue 3
509-513
EN
The aim of this study was to investigate the in vitro cytotoxicity of oseltamivir derivatives and determine their activity against A/H1N1/PR/8/34 and A/H3N2/HongKong/8/68 - strains of influenza virus. Antiviral activity of these compounds was determined by using two methods. MTT staining was used to assess the viability of MDCK cells infected with influenza viruses and treated with various concentrations of drugs. In parallel, the effect of drugs on viral replication was assessed using the hemagglutination test. The most toxic compounds were: OS-64, OS-35, OS-29, OS-27 and OS-25, whereas OS-11, OS-20 and OS-23 were the least toxic ones. Statistically significant antiviral effect at a higher virus dose was shown by compounds: OS-11, OS-20, OS-27, OS-35, and OS-64. H3N2 virus was sensitive to 10-times lower concentrations of OS-11 and OS-35 than H1N1. At a lower infection dose, the antiviral activity was observed for OS-11, OS 27, OS-35 and OS-20. OS-64 turned out to be effective only at a high concentration. OS-23 showed no antiviral effect.
5
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Characterization of mAb6-9-1 monoclonal antibody against hemagglutinin of avian influenza virus H5N1 and its engineered derivative, single-chain variable fragment antibody

88%
Sawicka R., Siedlecki P., Kalenik B., Radomski J., Sączyńska V., Porębska A., Szewczyk B., Sirko A., Góra-Sochacka A.
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2017
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vol. 64
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issue 1
85-92
EN
Hemagglutinin (HA), as a major surface antigen of influenza virus, is widely used as a target for production of neutralizing antibodies. Monoclonal antibody, mAb6-9-1, directed against HA of highly pathogenic avian influenza virus A/swan/Poland/305-135V08/2006(H5N1) was purified from mouse hybridoma cells culture and characterized. The antigenic specificity of mAb6-9-1 was verified by testing its cross-reactivity with several variants of HA. The mimotopes recognized by mAb6-9-1 were selected from two types of phage display peptide libraries. The comparative structural model of the HA variant used for antibody generation was developed to further facilitate epitope mapping. Based on the sequences of the affinity- selected polypeptides and the structural model of HA the epitope was located to the region near the receptor binding site (RBS). Such localization of the epitope recognized by mAb6-9-1 is in concordance with its moderate hemagglutination inhibiting activity and its antigenic specificity. Additionally, total RNA isolated from the hybridoma cell line secreting mAb6-9-1 was used for obtaining two variants of cDNA encoding recombinant single-chain variable fragment (scFv) antibody. To ensure high production level and solubility in bacterial expression system, the scFv fragments were produced as chimeric proteins in fusion with thioredoxin or displayed on a phage surface after cloning into the phagemid vector. Specificity and affinity of the recombinant soluble and phage-bound scFv were assayed by suitable variants of ELISA test. The observed differences in specificity were discussed.
6
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Antivirals - current trends in fighting influenza

88%
Król E., Rychłowska M., Szewczyk B.
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EN
Influenza virus infection is a major source of morbidity and mortality worldwide. Due to the variable effectiveness of existing vaccines, especially in the early stages of an epidemic, antiviral drugs represent the first line of defense against the virus. Currently, there are two major classes of anti-influenza drugs approved by the FDA for clinical use: M2 protein inhibitors (amantadine and rimantadine) and neuraminidase inhibitors (zanamivir and oseltamivir). However, increasing resistance to these available influenza antivirals among circulating influenza viruses highlights the need to develop alternative approaches for the prevention and/or treatment of influenza. This review presents an overview of currently available drugs for influenza treatment as well as summarizes some new antiviral strategies that are now being tested covering agents targeting both the viral proteins and the host-virus interaction. We discuss their mechanisms of action, resistance and the therapeutic potential as new antiviral drug for use in future influenza pandemics. Additionally, combination therapy based on these drugs is also described.
7
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Detection and differentiation of Newcastle disease virus and influenza virus by using duplex real-time PCR

75%
Nidzworski D., Wasilewska E., Smietanka K., Szewczyk B., Minta Z.
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2013
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vol. 60
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issue 3
475-480
EN
Newcastle disease virus (NDV), member of the Paramyxoviridae family and avian influenza virus (AIV), member of the Orthomyxoviridae family, are two main avian pathogens causing serious economic problems in poultry health. Both are enveloped, single-stranded, negative-sense RNA viruses and cause similar symptoms, ranging from sub-clinical infections to severe diseases, including decrease in egg production, acute respiratory syndrome, and high mortality. Similar symptoms hinder the differentiation of infection with the two viruses by standard veterinary procedures like clinical examination or necropsy. To overcome this problem, we have developed a new duplex real-time PCR assay for the detection and differentiation of these two viruses. Eighteen NDV strains, fourteen AIV strains, and twelve other (negative control) strains viruses were isolated from allantoic fluids of specific pathogen-free (SPF), embryonated eggs. Four-weeks-old SPF chickens were co-infected with both viruses (NDV - LaSota and AIV - H7N1). Swabs from cloaca and trachea were collected and examined. The results obtained in this study show that by using duplex real-time PCR, it was possible to detect and distinguish both viruses within less than three hours and with high sensitivity, even in case a bird was co-infected. Additionally, the results show the applicability of the real-time PCR assay in laboratory practice for the identification and differentiation of Newcastle disease and influenza A viruses in birds.
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