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Sample records for egg-based subunit influenza

  1. Advancements in the development of subunit influenza vaccines

    PubMed Central

    Zhang, Naru; Zheng, Bo-Jian; Lu, Lu; Zhou, Yusen; Jiang, Shibo; Du, Lanying

    2014-01-01

    The ongoing threat of influenza epidemics and pandemics has emphasized the importance of developing safe and effective vaccines against infections from divergent influenza viruses. In this review, we first introduce the structure and life cycle of influenza A viruses, describing major influenza A virus-caused pandemics. We then compare different types of influenza vaccines and discuss current advancements in the development of subunit influenza vaccines, particularly those based on nucleoprotein (NP), extracellular domain of matrix protein 2 (M2e) and hemagglutinin (HA) proteins. We also illustrate potential strategies for improving the efficacy of subunit influenza vaccines. PMID:25529753

  2. Intranasal immunization with influenza antigens conjugated with cholera toxin subunit B stimulates broad spectrum immunity against influenza viruses

    PubMed Central

    Li, Junwei; Arévalo, Maria T; Chen, Yanping; Posadas, Olivia; Smith, Jacob A; Zeng, Mingtao

    2014-01-01

    Frequent mutation of influenza viruses keep vaccinated and non-vaccinated populations vulnerable to new infections, causing serious burdens to public health and the economy. Vaccination with universal influenza vaccines would be the best way to effectively protect people from infection caused by mismatched or unforeseen influenza viruses. Presently, there is no FDA approved universal influenza vaccine. In this study, we expressed and purified a fusion protein comprising of influenza matrix 2 protein ectodomain peptides, a centralized influenza hemagglutinin stem region, and cholera toxin subunit B. Vaccination of BALB/c mice with this novel artificial antigen resulted in potent humoral immune responses, including induction of specific IgA and IgG, and broad protection against infection by multiple influenza viruses. Furthermore, our results demonstrated that when used as a mucosal antigen, cholera toxin subunit B improved antigen-stimulated T cell and memory B cell responses. PMID:24632749

  3. Depressed chemiluminescence response by influenza virus is enhanced after conjugation of viral subunits to muramyl dipeptide.

    PubMed Central

    Masihi, K N; Lange, W; Rohde-Schulz, B; Chedid, L; Jolivet, M

    1985-01-01

    The effect on respiratory burst of murine spleen cells after in vitro exposure to influenza virus, subunits, or subunits conjugated to muramyl dipeptide (MDP) was studied by luminol-dependent chemiluminescence (CL) in response to stimulation by zymosan. CL induced by infectious influenza A virus was depressed but could be elevated to normal levels when MDP was added together with a low, but not with a high, dose of the virus. Profound depression of CL was induced by high doses of influenza A/Brazil, A/Bangkok, and B/Singapore subunits. The same amounts of viral subunits conjugated to MDP restored or even enhanced the CL responses of spleen cells from BALB/c and C57BL/6 mice. Splenic cells from BALB/c mice generated higher levels of CL than did cells from C57BL/6 mice. PMID:4044031

  4. A Novel Influenza Virus Hemagglutinin-Respiratory Syncytial Virus (RSV) Fusion Protein Subunit Vaccine against Influenza and RSV

    PubMed Central

    Turner, Tiffany M.; Jones, Les P.; Tompkins, S. Mark

    2013-01-01

    Influenza A virus and respiratory syncytial virus (RSV) cause substantial morbidity and mortality afflicting the ends of the age spectrum during the autumn through winter months in the United States. The benefit of vaccination against RSV and influenza using a subunit vaccine to enhance immunity and neutralizing antibody was investigated. Influenza virus hemagglutinin (HA) and RSV fusion (F) protein were tested as vaccine components alone and in combination to explore the adjuvant properties of RSV F protein on HA immunity. Mice vaccinated with HA and F exhibited robust immunity that, when challenged, had reduced viral burden for both influenza and RSV. These studies show an enhancing and cross-protective benefit of F protein for anti-HA immunity. PMID:23903841

  5. Enhanced immune responses by skin vaccination with influenza subunit vaccine in young hosts.

    PubMed

    Koutsonanos, Dimitrios G; Esser, E Stein; McMaster, Sean R; Kalluri, Priya; Lee, Jeong-Woo; Prausnitz, Mark R; Skountzou, Ioanna; Denning, Timothy L; Kohlmeier, Jacob E; Compans, Richard W

    2015-09-01

    Skin has gained substantial attention as a vaccine target organ due to its immunological properties, which include a high density of professional antigen presenting cells (APCs). Previous studies have demonstrated the effectiveness of this vaccination route not only in animal models but also in adults. Young children represent a population group that is at high risk from influenza infection. As a result, this group could benefit significantly from influenza vaccine delivery approaches through the skin and the improved immune response it can induce. In this study, we compared the immune responses in young BALB/c mice upon skin delivery of influenza vaccine with vaccination by the conventional intramuscular route. Young mice that received 5 μg of H1N1 A/Ca/07/09 influenza subunit vaccine using MN demonstrated an improved serum antibody response (IgG1 and IgG2a) when compared to the young IM group, accompanied by higher numbers of influenza-specific antibody secreting cells (ASCs) in the bone marrow. In addition, we observed increased activation of follicular helper T cells and formation of germinal centers in the regional lymph nodes in the MN immunized group, rapid clearance of the virus from their lungs as well as complete survival, compared with partial protection observed in the IM-vaccinated group. Our results support the hypothesis that influenza vaccine delivery through the skin would be beneficial for protecting the high-risk young population from influenza infection. PMID:25744228

  6. PB2 subunit of avian influenza virus subtype H9N2: a pandemic risk factor.

    PubMed

    Sediri, Hanna; Thiele, Swantje; Schwalm, Folker; Gabriel, Gülsah; Klenk, Hans-Dieter

    2016-01-01

    Avian influenza viruses of subtype H9N2 that are found worldwide are occasionally transmitted to humans and pigs. Furthermore, by co-circulating with other influenza subtypes, they can generate new viruses with the potential to also cause zoonotic infections, as observed in 1997 with H5N1 or more recently with H7N9 and H10N8 viruses. Comparative analysis of the adaptive mutations in polymerases of different viruses indicates that their impact on the phylogenetically related H9N2 and H7N9 polymerases is higher than on the non-related H7N7 and H1N1pdm09 polymerases. Analysis of polymerase reassortants composed of subunits of different viruses demonstrated that the efficient enhancement of polymerase activity by H9N2-PB2 does not depend on PA and PB1. These observations suggest that the PB2 subunit of the H9N2 polymerase has a high adaptive potential and may therefore be an important pandemic risk factor. PMID:26560088

  7. Molecular Basis of mRNA Cap Recognition by Influenza B Polymerase PB2 Subunit.

    PubMed

    Xie, Lili; Wartchow, Charles; Shia, Steven; Uehara, Kyoko; Steffek, Micah; Warne, Robert; Sutton, James; Muiru, Gladys T; Leonard, Vincent H J; Bussiere, Dirksen E; Ma, Xiaolei

    2016-01-01

    Influenza virus polymerase catalyzes the transcription of viral mRNAs by a process known as "cap-snatching," where the 5'-cap of cellular pre-mRNA is recognized by the PB2 subunit and cleaved 10-13 nucleotides downstream of the cap by the endonuclease PA subunit. Although this mechanism is common to both influenza A (FluA) and influenza B (FluB) viruses, FluB PB2 recognizes a wider range of cap structures including m(7)GpppGm-, m(7)GpppG-, and GpppG-RNA, whereas FluA PB2 utilizes methylated G-capped RNA specifically. Biophysical studies with isolated PB2 cap-binding domain (PB2(cap)) confirm that FluB PB2 has expanded mRNA cap recognition capability, although the affinities toward m(7)GTP are significantly reduced when compared with FluA PB2. The x-ray co-structures of the FluB PB2(cap) with bound cap analogs m(7)GTP and GTP reveal an inverted GTP binding mode that is distinct from the cognate m(7)GTP binding mode shared between FluA and FluB PB2. These results delineate the commonalities and differences in the cap-binding site between FluA and FluB PB2 and will aid structure-guided drug design efforts to identify dual inhibitors of both FluA and FluB PB2. PMID:26559973

  8. Targeting the HA2 subunit of influenza A virus hemagglutinin via CD40L provides universal protection against diverse subtypes.

    PubMed

    Fan, X; Hashem, A M; Chen, Z; Li, C; Doyle, T; Zhang, Y; Yi, Y; Farnsworth, A; Xu, K; Li, Z; He, R; Li, X; Wang, J

    2015-01-01

    The influenza viral hemagglutinin (HA) is comprised of two subunits. Current influenza vaccine predominantly induces neutralizing antibodies (Abs) against the HA1 subunit, which is constantly evolving in unpredictable fashion. The other subunit, HA2, however, is highly conserved but largely shielded by the HA head domain. Thus, enhancing immune response against HA2 could potentially elicit broadly inhibitory Abs. We generated a recombinant adenovirus (rAd) encoding secreted fusion protein, consisting of codon-optimized HA2 subunit of influenza A/California/7/2009(H1N1) virus fused to a trimerized form of murine CD40L, and determined its ability of inducing protective immunity upon intranasal administration. We found that mice immunized with this recombinant viral vaccine were completely protected against lethal challenge with divergent influenza A virus subtypes including H1N1, H3N2, and H9N2. Codon-optimization of HA2 as well as the use of CD40L as a targeting ligand/molecular adjuvant were indispensable to enhance HA2-specific mucosal IgA and serum IgG levels. Moreover, induction of HA2-specific T-cell responses was dependent on CD40L, as rAd secreting HA2 subunit without CD40L failed to induce any significant levels of T-cell cytokines. Finally, sera obtained from immunized mice were capable of inhibiting 13 subtypes of influenza A viruses in vitro. These results provide proof of concept for a prototype HA2-based universal influenza vaccine. PMID:25052763

  9. Single-dose monomeric HA subunit vaccine generates full protection from influenza challenge.

    PubMed

    Mallajosyula, Jyothi K; Hiatt, Ernie; Hume, Steve; Johnson, Ashley; Jeevan, Trushar; Chikwamba, Rachel; Pogue, Gregory P; Bratcher, Barry; Haydon, Hugh; Webby, Richard J; McCormick, Alison A

    2014-01-01

    Recombinant subunit vaccines are an efficient strategy to meet the demands of a possible influenza pandemic, because of rapid and scalable production. However, vaccines made from recombinant hemagglutinin (HA) subunit protein are often of low potency, requiring high dose or boosting to generate a sustained immune response. We have improved the immunogenicity of a plant-made HA vaccine by chemical conjugation to the surface of the Tobacco mosaic virus (TMV) which is non infectious in mammals. We have previously shown that TMV is taken up by mammalian dendritic cells and is a highly effective antigen carrier. In this work, we tested several TMV-HA conjugation chemistries, and compared immunogenicity in mice as measured by anti-HA IgG titers and hemagglutination inhibition (HAI). Importantly, pre-existing immunity to TMV did not reduce initial or boosted titers. Further optimization included dosing with and without alum or oil-in water adjuvants. Surprisingly, we were able to stimulate potent immunogenicity and HAI titers with a single 15 µg dose of HA as a TMV conjugate. We then evaluated the efficacy of the TMV-HA vaccine in a lethal virus challenge in mice. Our results show that a single dose of the TMV-HA conjugate vaccine is sufficient to generate 50% survival, or 100% survival with adjuvant, compared with 10% survival after vaccination with a commercially available H1N1 vaccine. TMV-HA is an effective dose-sparing influenza vaccine, using a single-step process to rapidly generate large quantities of highly effective flu vaccine from an otherwise low potency HA subunit protein. PMID:24378714

  10. The influenza A virus PB2 polymerase subunit is required for the replication of viral RNA.

    PubMed Central

    Perales, B; Ortín, J

    1997-01-01

    The transcription and replication of influenza virus RNA (vRNA) were reconstituted in vivo. The experimental approach involved the transfection of plasmids encoding the viral subunits of the polymerase and the nucleoprotein into cells infected with a vaccinia virus recombinant virus expressing the T7 RNA polymerase. As templates, one of two model RNAs was transfected: vNSZ or cNSZ RNA. The RNAs were 240 nucleotides in length, contained the terminal sequences of the NS viral segment, and were of negative or positive polarity, respectively. The accumulation of cRNA and mRNA in cells transfected with vNSZ RNA and the accumulation of vRNA and mRNA in cells transfected with cNSZ RNA were determined by RNase protection assays with labeled vNSZ-L or cNSZ-L probes. The patterns of protected bands obtained indicated that both cRNA replication intermediate and mRNA accumulated when the system was reconstituted with vNSZ RNA. Likewise, both vRNA and mRNA accumulated after reconstitution with cNSZ RNA. The reconstitution of incomplete systems in which any of the subunits of the polymerase or the model RNA were omitted was completely negative for the accumulation of cRNA or vRNA, indicating that the presence of the PB2 subunit in the polymerase is required for replication of vRNA. PMID:8995663

  11. Immunologic and Structural Relationships of the Minor Pilus Subunits among Haemophilus influenzae Isolates

    PubMed Central

    McCrea, Kirk W.; St. Sauver, Jennifer L.; Marrs, Carl F.; Clemans, Daniel; Gilsdorf, Janet R.

    1998-01-01

    Two proteins, HifD and HifE, have been identified as structural components of Haemophilus influenzae pili. Both are localized at the pilus tip, and HifE appears to mediate pilus adherence to host cells. In this study we examined the immunologic and structural diversity of these pilus subunits among type b H. influenzae (Hib) and nontypeable H. influenzae (NTHI) strains. Western immunoblot analysis revealed that antibodies directed against the C terminus of HifD and HifE from Hib strain Eagan bound to HifD and HifE proteins, respectively, of all piliated Hib and NTHI strains tested. Whole-cell enzyme-linked immunosorbent assays showed that antibodies specific for native HifD or HifE of strain Eagan also bound to all piliated Hib strains but did not bind to the piliated NTHI strains. Antibodies against HifE of strain Eagan inhibited the binding of Hib to human erythrocytes but did not inhibit the binding of NTHI strains. Restriction fragment length polymorphism (RFLP) analysis was used to determine strain-to-strain structural differences within hifD and hifE genes, either by PCR or by nucleotide sequence analysis. DNA and derived amino acid sequence analyses of HifD and HifE confirmed the uniqueness of the RFLP types. The hifD and hifE genes of all type b strains showed identical restriction patterns. Analysis of hifD and hifE genes from the NTHI strains, however, revealed seven unique RFLP patterns, suggesting that these genes encode proteins with diverse primary structures. These results indicate that HifD and HifE are immunologically and structurally similar among the Hib strains but vary among the NTHI strains. PMID:9746580

  12. Influenza A virus hemagglutinin protein subunit vaccine elicits vaccine-associated enhanced respiratory disease in pigs.

    PubMed

    Rajão, Daniela S; Loving, Crystal L; Gauger, Phillip C; Kitikoon, Pravina; Vincent, Amy L

    2014-09-01

    Vaccine-associated enhanced respiratory disease (VAERD) can occur when pigs are challenged with heterologous virus in the presence of non-neutralizing but cross-reactive antibodies elicited by whole inactivated virus (WIV) vaccine. The aim of this study was to compare the effects of heterologous δ1-H1N2 influenza A virus (IAV) challenge of pigs after vaccination with 2009 pandemic H1N1 virus (H1N1pdm09) recombinant hemagglutinin (HA) subunit vaccine (HA-SV) or temperature-sensitive live attenuated influenza virus (LAIV) vaccine, and to assess the role of immunity to HA in the development of VAERD. Both HA-SV and LAIV vaccines induced high neutralizing antibodies to virus with homologous HA (H1N1pdm09), but not heterologous challenge virus (δ1-H1N2). LAIV partially protected pigs, resulting in reduced virus shedding and faster viral clearance, as no virus was detected in the lungs by 5 days post infection (dpi). HA-SV vaccinated pigs developed more severe lung and tracheal lesions consistent with VAERD following challenge. These results demonstrate that the immune response against the HA protein alone is sufficient to cause VAERD following heterologous challenge. PMID:25077416

  13. Cross-protection of Lactococcus lactis-displayed HA2 subunit against homologous and heterologous influenza A viruses in mice.

    PubMed

    Lei, Han; Peng, Xiaojue; Zhao, Daxian; Jiao, Huifeng; Ouyang, Jiexiu

    2015-12-01

    Current influenza vaccines provide strain-specific protection against homologous subtypes and need to be updated annually. Therefore, it is essential to develop a universal vaccine that would induce broadly cross-protective immunity against homologous and heterologous influenza A viruses. The highly conserved HA2 subunit is a promising candidate for developing a universal influenza vaccine. Here, we hypothesized that the HA2 subunit could be displayed on the surface of Lactococcus lactis (L. lactis), using Spax as an anchor protein (L. lactis/pNZ8008-Spax-HA2) and that L. lactis/pNZ8008-Spax-HA2 would have immunogenicity by oral administration without the use of adjuvant in the mouse model. To address this hypothesis, we show that oral vaccination of mice with L. lactis/pNZ8008-Spax-HA2 elicited significant humoral and mucosal immune responses. Importantly, L. lactis/pNZ8008-Spax-HA2 provided 100% protection against homologous H5N1 or heterologous H1N1 virus challenge. These results suggest that an HA2 subunit presented on the surface of L. lactis is an effective universal vaccine candidate against influenza A viruses in the poultry industry and in humans. PMID:26358264

  14. Intermonomer Interactions in Hemagglutinin Subunits HA1 and HA2 Affecting Hemagglutinin Stability and Influenza Virus Infectivity

    PubMed Central

    DeFeo, Christopher J.; Alvarado-Facundo, Esmeralda; Vassell, Russell

    2015-01-01

    ABSTRACT Influenza virus hemagglutinin (HA) mediates virus entry by binding to cell surface receptors and fusing the viral and endosomal membranes following uptake by endocytosis. The acidic environment of endosomes triggers a large-scale conformational change in the transmembrane subunit of HA (HA2) involving a loop (B loop)-to-helix transition, which releases the fusion peptide at the HA2 N terminus from an interior pocket within the HA trimer. Subsequent insertion of the fusion peptide into the endosomal membrane initiates fusion. The acid stability of HA is influenced by residues in the fusion peptide, fusion peptide pocket, coiled-coil regions of HA2, and interactions between the surface (HA1) and HA2 subunits, but details are not fully understood and vary among strains. Current evidence suggests that the HA from the circulating pandemic 2009 H1N1 influenza A virus [A(H1N1)pdm09] is less stable than the HAs from other seasonal influenza virus strains. Here we show that residue 205 in HA1 and residue 399 in the B loop of HA2 (residue 72, HA2 numbering) in different monomers of the trimeric A(H1N1)pdm09 HA are involved in functionally important intermolecular interactions and that a conserved histidine in this pair helps regulate HA stability. An arginine-lysine pair at this location destabilizes HA at acidic pH and mediates fusion at a higher pH, while a glutamate-lysine pair enhances HA stability and requires a lower pH to induce fusion. Our findings identify key residues in HA1 and HA2 that interact to help regulate H1N1 HA stability and virus infectivity. IMPORTANCE Influenza virus hemagglutinin (HA) is the principal antigen in inactivated influenza vaccines and the target of protective antibodies. However, the influenza A virus HA is highly variable, necessitating frequent vaccine changes to match circulating strains. Sequence changes in HA affect not only antigenicity but also HA stability, which has important implications for vaccine production, as well

  15. Expression of the hemagglutinin HA1 subunit of the equine influenza virus using a baculovirus expression system.

    PubMed

    Sguazza, Guillermo H; Fuentealba, Nadia A; Tizzano, Marco A; Galosi, Cecilia M; Pecoraro, Marcelo R

    2013-01-01

    Equine influenza virus is a leading cause of respiratory disease in horses worldwide. Disease prevention is by vaccination with inactivated whole virus vaccines. Most current influenza vaccines are generated in embryonated hens' eggs. Virions are harvested from allantoic fluid and chemically inactivated. Although this system has served well over the years, the use of eggs as the substrate for vaccine production has several well-recognized disadvantages (cost, egg supply, waste disposal and yield in eggs). The aim of this study was to evaluate a baculovirus system as a potential method for producing recombinant equine influenza hemagglutinin to be used as a vaccine. The hemagglutinin ectodomain (HA1 subunit) was cloned and expressed using a baculovirus expression vector. The expression was determined by SDS-PAGE and immunoblotting. A high yield, 20μg/ml of viral protein, was obtained from recombinant baculovirus-infected cells. The immune response in BALB/c mice was examined following rHA1 inoculation. Preliminary results show that recombinant hemagglutinin expressed from baculovirus elicits a strong antibody response in mice; therefore it could be used as an antigen for subunit vaccines and diagnostic tests. PMID:24401775

  16. Multi-target parallel processing approach for gene-to-structure determination of the influenza polymerase PB2 subunit.

    PubMed

    Armour, Brianna L; Barnes, Steve R; Moen, Spencer O; Smith, Eric; Raymond, Amy C; Fairman, James W; Stewart, Lance J; Staker, Bart L; Begley, Darren W; Edwards, Thomas E; Lorimer, Donald D

    2013-01-01

    Pandemic outbreaks of highly virulent influenza strains can cause widespread morbidity and mortality in human populations worldwide. In the United States alone, an average of 41,400 deaths and 1.86 million hospitalizations are caused by influenza virus infection each year (1). Point mutations in the polymerase basic protein 2 subunit (PB2) have been linked to the adaptation of the viral infection in humans (2). Findings from such studies have revealed the biological significance of PB2 as a virulence factor, thus highlighting its potential as an antiviral drug target. The structural genomics program put forth by the National Institute of Allergy and Infectious Disease (NIAID) provides funding to Emerald Bio and three other Pacific Northwest institutions that together make up the Seattle Structural Genomics Center for Infectious Disease (SSGCID). The SSGCID is dedicated to providing the scientific community with three-dimensional protein structures of NIAID category A-C pathogens. Making such structural information available to the scientific community serves to accelerate structure-based drug design. Structure-based drug design plays an important role in drug development. Pursuing multiple targets in parallel greatly increases the chance of success for new lead discovery by targeting a pathway or an entire protein family. Emerald Bio has developed a high-throughput, multi-target parallel processing pipeline (MTPP) for gene-to-structure determination to support the consortium. Here we describe the protocols used to determine the structure of the PB2 subunit from four different influenza A strains. PMID:23851357

  17. Structure-Based Drug Design Targeting a Subunit Interaction of Influenza Virus RNA Polymerase

    NASA Astrophysics Data System (ADS)

    Sugiyama, Kanako; Obayashi, Eiji; Yoshida, Hisashi; Park, Sam-Yong

    Influenza A virus is a major human and animal pathogen with the potential to cause catastrophic loss of life. Influenza virus reproduces rapidly, mutates frequently, and occasionally crosses species barriers. The recent emergence of swine-origin influenza H1N1 and avian influenza related to highly pathogenic forms of the human virus has highlighted the urgent need for new effective treatments. Here, we describe two crystal structures of complexes made by fragments of PA and PB1, and PB1 and PB2. These novel interfaces are surprisingly small, yet they play a crucial role in regulating the 250 kDa polymerase complex, and are completely conserved among swine, avian and human influenza viruses. Given their importance to viral replication and strict conservation, the PA/PB1 and PB1/PB2 interfaces appear to be promising targets for novel anti-influenza drugs of use against all strains of influenza A virus. It is hoped that the structures presented here will assist the search for such compounds.

  18. Identification of a small-molecule inhibitor of influenza virus via disrupting the subunits interaction of the viral polymerase.

    PubMed

    Yuan, Shuofeng; Chu, Hin; Zhao, Hanjun; Zhang, Ke; Singh, Kailash; Chow, Billy K C; Kao, Richard Y T; Zhou, Jie; Zheng, Bo-Jian

    2016-01-01

    Assembly of the heterotrimeric influenza virus polymerase complex from the individual subunits PB1, PA, and PB2 is a prerequisite for viral replication, in which the interaction between the C terminal of PA (PAC) and the N-terminal of PB1 (PB1N) may be a desired target for antiviral development. In this study, we compared the feasibility of high throughput screening by enzyme-linked immunosorbent assay (ELISA) and fluorescence polarization assay. Among the two, ELISA was demonstrated to own broader dynamic range so that it was used for screening inhibitors that blocked PAC and PB1N interaction. Several binding inhibitors of PAC-PB1N were identified and subsequently tested for the antiviral efficacy. Apparently, 3-(2-chlorophenyl)-6-ethyl-7-methyl[1,2,4]triazolo[4,3-a]pyrimidin-5-ol, designated ANA-1, was found to be a strong inhibitor of viral polymerase activity and act as a potent antiviral agent against the infections of multiple subtypes of influenza A virus, including H1N1, H3N2, H5N1, H7N7, H7N9 and H9N2 subtypes, in cell cultures. Intranasal administration of ANA-1 protected mice from lethal challenge and reduced lung viral loads in H1N1 virus infected BALB/c mice. Docking analyses predicted that ANA-1 bound to an allosteric site of PAC, which might cause conformational changes thereby disrupting the PAC-PB1N interaction. Overall, our study has identified a novel compound with potential to be developed as an anti-influenza drug. PMID:26593979

  19. Particle and subunit-based hemagglutinin vaccines provide protective efficacy against H1N1 influenza in pigs.

    PubMed

    Hernandez, Luis A; Miller, Cathy L; Vaughn, Eric M

    2016-08-15

    The increasing diversity of influenza strains circulating in swine herds escalates the potential for the emergence of novel pandemic viruses and highlights the need for swift development of new vaccines. Baculovirus has proven to be a flexible platform for the generation of recombinant forms of hemagglutinin (HA) including subunit, VLP-displayed, and baculovirus-displayed antigens. These presentations have been shown to be efficacious in mouse, chicken, and ferret models but little is known about their immunogenicity in pigs. To assess the utility of these HA presentations in swine, Baculovirus constructs expressing HA fused to swine IgG2a Fc, displayed in a FeLV gag VLP, or displayed in the baculoviral envelope were generated. Vaccines formulated with these antigens wer The e administered to groups of pigs who were subsequently challenged with H1α cluster H1N1 swine influenza virus (SIV) A/Swine/Indiana/1726/88. Our results demonstrate that vaccination with any of these three vaccines elicits robust hemagglutinin inhibition titers in the serum and decreased the severity of SIV-associated lung lesions after challenge when compared to placebo-vaccinated controls. In addition, the number of pigs with virus detected in the lungs and nasal passages was reduced. Taken together, the results demonstrate that these recombinant approaches expressed with the baculovirus expression vector system may be viable options for development of SIV vaccines for swine. PMID:27374905

  20. Influenza subunit vaccine coated microneedle patches elicit comparable immune responses to intramuscular injection in guinea pigs.

    PubMed

    Kommareddy, S; Baudner, B C; Bonificio, A; Gallorini, S; Palladino, G; Determan, A S; Dohmeier, D M; Kroells, K D; Sternjohn, J R; Singh, M; Dormitzer, P R; Hansen, K J; O'Hagan, D T

    2013-07-25

    Delivery of influenza vaccine using innovative approaches such as microneedles has been researched extensively in the past decade. In this study we present concentration followed by formulation and coating of monobulks from 2008/2009 seasonal vaccine on to 3M's solid microstructured transdermal system (sMTS) by a GMP-scalable process. The hemagglutinin (HA) in monobulks was concentrated by tangential flow filtration (TFF) to achieve HA concentrations as high as 20mg/ml. The stability of the coated antigens was evaluated by the functional assay, single radial immunodiffusion (SRID). The data generated show stability of the coated antigen upon storage at 4°C and room temperature in the presence of desiccant for at least 8 weeks. Freeze-thaw stability data indicate the stability of the coated antigen in stressed conditions. The vaccine coated microstructures were evaluated in vivo in a guinea pig model, and resulted in immune titers comparable to the traditional trivalent vaccine administered intramuscularly. The data presented indicate the potential use of the technology in delivery of influenza vaccine. This paper also addresses the key issues of stability of coated antigen, reproducibility and scalability of the processes used in preparation of influenza vaccine coated microneedle patches that are important in developing a successful product. PMID:23398932

  1. Influenza.

    PubMed

    Labella, Angelena M; Merel, Susan E

    2013-07-01

    Influenza is a common virus whose ability to change its genetic makeup allows for disease of pandemic proportion. This article summarizes the different strains of influenza circulating in the United States for the past century, the diagnosis and treatment of influenza, as well as the different ways to prevent disease. This information will be of value to clinicians caring for patients both in the hospital and in the community. PMID:23809717

  2. A Fusion Protein Based on the Second Subunit of Hemagglutinin of Influenza A/H2N2 Viruses Provides Cross Immunity

    PubMed Central

    Stepanova, L. A.; Sergeeva, M. V.; Shuklina, M. A.; Shaldzhyan, A. A.; Potapchuk, M. V.; Korotkov, A. V.; Tsybalova, L. M.

    2016-01-01

    Conserved fragments of the second subunit of hemagglutinin (HA2) are of great interest for the design of vaccine constructs that can provide protective immunity against influenza A viruses of different subtypes. A recombinant fusion protein, FlgMH, was constructed on the basis of flagellin and a highly conserved HA2 fragment (35–107) of influenza viruses of the subtype A/H2N2, containing B cell, CD4+ T cell, and CD8+ T cell epitopes. The native conformation of the HA2 fragment was partially preserved upon its attachment to the C-terminus of flagellin within the recombinant fusion protein FlgMH. FlgMH was shown to stimulate a mixed Th1/Th2 response of cross-reactive antibodies, which bind to influenza viruses of the first phylogenetic group (H1, H2, H5), to the target sequence as well as the induction of specific cytotoxic T cells (CD3+CD8+IFNγ+). Immunization with the recombinant protein protected animals from a lethal influenza infection. The developed FlgMH protein is a promising agent that may be included in an influenza vaccine with a wide spectrum of action which will be able to stimulate the T and B cell immune responses. PMID:27437146

  3. A Fusion Protein Based on the Second Subunit of Hemagglutinin of Influenza A/H2N2 Viruses Provides Cross Immunity.

    PubMed

    Stepanova, L A; Sergeeva, M V; Shuklina, M A; Shaldzhyan, A A; Potapchuk, M V; Korotkov, A V; Tsybalova, L M

    2016-01-01

    Conserved fragments of the second subunit of hemagglutinin (HA2) are of great interest for the design of vaccine constructs that can provide protective immunity against influenza A viruses of different subtypes. A recombinant fusion protein, FlgMH, was constructed on the basis of flagellin and a highly conserved HA2 fragment (35-107) of influenza viruses of the subtype A/H2N2, containing B cell, CD4+ T cell, and CD8+ T cell epitopes. The native conformation of the HA2 fragment was partially preserved upon its attachment to the C-terminus of flagellin within the recombinant fusion protein FlgMH. FlgMH was shown to stimulate a mixed Th1/Th2 response of cross-reactive antibodies, which bind to influenza viruses of the first phylogenetic group (H1, H2, H5), to the target sequence as well as the induction of specific cytotoxic T cells (CD3+CD8+IFNγ+). Immunization with the recombinant protein protected animals from a lethal influenza infection. The developed FlgMH protein is a promising agent that may be included in an influenza vaccine with a wide spectrum of action which will be able to stimulate the T and B cell immune responses. PMID:27437146

  4. Influenza

    PubMed Central

    2009-01-01

    Introduction During the autumn-winter months (influenza seasons), influenza circulates more frequently, causing a greater proportion of influenza-like illness, and sometimes serious seasonal epidemics. The incidence of infection depends on the underlying immunity of the population. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of vaccines to prevent influenza? What are the effects of antiviral chemoprophylaxis of influenza? What are the effects of antiviral medications to treat influenza? We searched: Medline, Embase, The Cochrane Library, and other important databases up to June 2008 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 21 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. Conclusions In this systematic review we present information relating to the effectiveness and safety of the following interventions: vaccines, amantadine, oseltamivir, zanamivir, rimantadine. PMID:19445759

  5. The PB2 Subunit of the Influenza Virus RNA Polymerase Affects Virulence by Interacting with the Mitochondrial Antiviral Signaling Protein and Inhibiting Expression of Beta Interferon▿

    PubMed Central

    Graef, Katy M.; Vreede, Frank T.; Lau, Yuk-Fai; McCall, Amber W.; Carr, Simon M.; Subbarao, Kanta; Fodor, Ervin

    2010-01-01

    The PB2 subunit of the influenza virus RNA polymerase is a major virulence determinant of influenza viruses. However, the molecular mechanisms involved remain unknown. It was previously shown that the PB2 protein, in addition to its nuclear localization, also accumulates in the mitochondria. Here, we demonstrate that the PB2 protein interacts with the mitochondrial antiviral signaling protein, MAVS (also known as IPS-1, VISA, or Cardif), and inhibits MAVS-mediated beta interferon (IFN-β) expression. In addition, we show that PB2 proteins of influenza viruses differ in their abilities to associate with the mitochondria. In particular, the PB2 proteins of seasonal human influenza viruses localize to the mitochondria while PB2 proteins of avian influenza viruses are nonmitochondrial. This difference in localization is caused by a single amino acid polymorphism in the PB2 mitochondrial targeting signal. In order to address the functional significance of the mitochondrial localization of the PB2 protein in vivo, we have generated two recombinant human influenza viruses encoding either mitochondrial or nonmitochondrial PB2 proteins. We found that the difference in the mitochondrial localization of the PB2 proteins does not affect the growth of these viruses in cell culture. However, the virus encoding the nonmitochondrial PB2 protein induces higher levels of IFN-β and, in an animal model, is attenuated compared to the isogenic virus encoding a mitochondrial PB2. Overall this study implicates the PB2 protein in the regulation of host antiviral innate immune pathways and suggests an important role for the mitochondrial association of the PB2 protein in determining virulence. PMID:20538852

  6. The adjuvants MF59 and LT-K63 enhance the mucosal and systemic immunogenicity of subunit influenza vaccine administered intranasally in mice.

    PubMed

    Barchfeld, G L; Hessler, A L; Chen, M; Pizza, M; Rappuoli, R; Van Nest, G A

    1999-02-26

    Commercial influenza vaccines generate serum antibody, but not local IgA. Influenza vaccines that induce both serum and secretory antibody are more likely to protect against infection and disease progression. The adjuvants MF59 and LT-K63 were tested intramuscularly and intranasally with subunit HA. In naive mice, intranasal adjuvant effect was more apparent when included with the first than second immunization. In previously infected mice, intranasal adjuvants had little effect on serum antibodies and were most effective for nasal antibodies after the second immunization. Overall, both adjuvants enhanced anti-HA IgA and IgG by intranasal vaccination whereas, by intramuscular vaccination, they only enhanced serum IgG. PMID:10067675

  7. Influenza

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The term "influenza" originally referred to epidemics of acute, rapidly spreading catarrhal fevers of humans caused by viruses in the family Orthomyxoviridae. Today, orthomyxoviruses are recognized as the cause of significant numbers of natural infections and disease, usually of the upper respirato...

  8. Mucosally administered Lactobacillus surface-displayed influenza antigens (sM2 and HA2) with cholera toxin subunit A1 (CTA1) Induce broadly protective immune responses against divergent influenza subtypes.

    PubMed

    Li, Rui; Chowdhury, Mohammed Y E; Kim, Jae-Hoon; Kim, Tae-Hwan; Pathinayake, Prabuddha; Koo, Wan-Seo; Park, Min-Eun; Yoon, Ji-Eun; Roh, Jong-Bok; Hong, Seung-Pyo; Sung, Moon-Hee; Lee, Jong-Soo; Kim, Chul-Joong

    2015-09-30

    The development of a universal influenza vaccine that provides broad cross protection against existing and unforeseen influenza viruses is a critical challenge. In this study, we constructed and expressed conserved sM2 and HA2 influenza antigens with cholera toxin subunit A1 (CTA1) on the surface of Lactobacillus casei (pgsA-CTA1sM2HA2/L. casei). Oral and nasal administrations of recombinant L. casei into mice resulted in high levels of serum immunoglobulin G (IgG) and their isotypes (IgG1 & IgG2a) as well as mucosal IgA. The mucosal administration of pgsA-CTA1sM2HA2/L. casei may also significantly increase the levels of sM2- or HA2-specific cell-mediated immunity because increased release of both IFN-γ and IL-4 was observed. The recombinant pgsA-CTA1sM2HA2/L. casei provided better protection of BALB/c mice against 10 times the 50% mouse lethal doses (MLD50) of homologous A/EM/Korea/W149/06(H5N1) or A/Aquatic bird/Korea/W81/2005 (H5N2) and heterologous A/Puerto Rico/8/34(H1N1), or A/Chicken/Korea/116/2004(H9N2) or A/Philippines/2/08(H3N2) viruses, compared with L. casei harboring sM2HA2 and also the protection was maintained up to seven months after administration. These results indicate that recombinant L. casei expressing the highly conserved sM2, HA2 of influenza and CTA1 as a mucosal adjuvant could be a potential mucosal vaccine candidate or tool to protect against divergent influenza viruses for human and animal. PMID:26210951

  9. Immunopotentiation of Different Adjuvants on Humoral and Cellular Immune Responses Induced by HA1-2 Subunit Vaccines of H7N9 Influenza in Mice.

    PubMed

    Song, Li; Xiong, Dan; Hu, Maozhi; Kang, Xilong; Pan, Zhiming; Jiao, Xinan

    2016-01-01

    In spring 2013, human infections with a novel avian influenza A (H7N9) virus were reported in China. The number of cases has increased with over 200 mortalities reported to date. However, there is currently no vaccine available for the H7 subtype of influenza A virus. Virus-specific cellular immune responses play a critical role in virus clearance during influenza infection. In this study, we undertook a side-by-side evaluation of two different adjuvants, Salmonella typhimurium flagellin (fliC) and polyethyleneimine (PEI), through intraperitoneal administration to assess their effects on the immunogenicity of the recombinant HA1-2 subunit vaccine of H7N9 influenza. The fusion protein HA1-2-fliC and HA1-2 combined with PEI could induce significantly higher HA1-2-specific IgG and hemagglutination inhibition titers than HA1-2 alone at 12 days post-boost, with superior HA1-2 specific IgG titers in the HA1-2-fliC group compared with the PEI adjuvanted group. The PEI adjuvanted vaccine induced higher IgG1/IgG2a ratio and significantly increased numbers of IFN-γ- and IL-4-producing cells than HA1-2 alone, suggesting a mixed Th1/Th2-type cellular immune response with a Th2 bias. Meanwhile, the HA1-2-fliC induced higher IgG2a and IgG1 levels, which is indicative of a mixed Th1/Th2-type profile. Consistent with this, significant levels, and equal numbers, of IFN-γ- and IL-4-producing cells were detected after HA1-2-fliC vaccination. Moreover, the marked increase in CD69 expression and the proliferative index with the HA1-2-fliC and PEI adjuvanted vaccines indicated that both adjuvanted vaccine candidates effectively induced antigen-specific cellular immune responses. Taken together, our findings indicate that the two adjuvanted vaccine candidates elicit effective and HA1-2-specific humoral and cellular immune responses, offering significant promise for the development of a successful recombinant HA1-2 subunit vaccine for H7N9 influenza. PMID:26930068

  10. Immunopotentiation of Different Adjuvants on Humoral and Cellular Immune Responses Induced by HA1-2 Subunit Vaccines of H7N9 Influenza in Mice

    PubMed Central

    Song, Li; Xiong, Dan; Hu, Maozhi; Kang, Xilong; Pan, Zhiming; Jiao, Xinan

    2016-01-01

    In spring 2013, human infections with a novel avian influenza A (H7N9) virus were reported in China. The number of cases has increased with over 200 mortalities reported to date. However, there is currently no vaccine available for the H7 subtype of influenza A virus. Virus-specific cellular immune responses play a critical role in virus clearance during influenza infection. In this study, we undertook a side-by-side evaluation of two different adjuvants, Salmonella typhimurium flagellin (fliC) and polyethyleneimine (PEI), through intraperitoneal administration to assess their effects on the immunogenicity of the recombinant HA1-2 subunit vaccine of H7N9 influenza. The fusion protein HA1-2-fliC and HA1-2 combined with PEI could induce significantly higher HA1-2-specific IgG and hemagglutination inhibition titers than HA1-2 alone at 12 days post-boost, with superior HA1-2 specific IgG titers in the HA1-2-fliC group compared with the PEI adjuvanted group. The PEI adjuvanted vaccine induced higher IgG1/IgG2a ratio and significantly increased numbers of IFN-γ- and IL-4-producing cells than HA1-2 alone, suggesting a mixed Th1/Th2-type cellular immune response with a Th2 bias. Meanwhile, the HA1-2-fliC induced higher IgG2a and IgG1 levels, which is indicative of a mixed Th1/Th2-type profile. Consistent with this, significant levels, and equal numbers, of IFN-γ- and IL-4-producing cells were detected after HA1-2-fliC vaccination. Moreover, the marked increase in CD69 expression and the proliferative index with the HA1-2-fliC and PEI adjuvanted vaccines indicated that both adjuvanted vaccine candidates effectively induced antigen-specific cellular immune responses. Taken together, our findings indicate that the two adjuvanted vaccine candidates elicit effective and HA1-2-specific humoral and cellular immune responses, offering significant promise for the development of a successful recombinant HA1-2 subunit vaccine for H7N9 influenza. PMID:26930068

  11. Specific Residues of PB2 and PA Influenza Virus Polymerase Subunits Confer the Ability for RNA Polymerase II Degradation and Virus Pathogenicity in Mice

    PubMed Central

    Llompart, C. M.

    2014-01-01

    ABSTRACT Influenza virus transcription requires functional coupling with cellular transcription for the cap-snatching process. Despite this fact, RNA polymerase II (RNAP II) is degraded during infection in a process triggered by the viral polymerase. Reassortant viruses from the A/PR/8/34 (PR8) strain that induce (hvPR8) or do not induce (lvPR8) RNAP II degradation led to the identification of PA and PB2 subunits as responsible for the degradation process. Three changes in the PB2 sequence (I105M, N456D, and I504V) and two in PA (Q193H and I550L) differentiate PA and PB2 of lvPR8 from those of hvPR8. Using recombinant viruses, we observed that changes at position 504 of PB2, together with 550 of PA, confer the ability on lvPR8 for RNAP II degradation and, conversely, abolish hvPR8 degradation capacity. Since hvPR8 is more pathogenic than lvPR8 in mice, we tested the potential contribution of RNAP II degradation in a distant viral strain, the 2009 pandemic A/California/04/09 (CAL) virus, whose PA and PB2 subunits are of avian origin. As in the hvPR8 virus, mutations at positions 504 of PB2 and 550 of PA in CAL virus abolished its RNAP II degradation capacity. Moreover, in an in vivo model, the CAL-infected mice lost more body weight, and 75% lethality was observed in this situation compared with 100% survival in mutant-CAL- or mock-infected animals. These results confirm the involvement of specific PB2 and PA residues in RNAP II degradation, which correlates with pathogenicity in mice of viruses containing human or avian polymerase PB2 and PA subunits. IMPORTANCE The influenza virus polymerase induces the degradation of RNAP II, which probably cooperates to avoid the antiviral response. Here, we have characterized two specific residues located in the PA and PB2 polymerase subunits that mediate this degradation in different influenza viruses. Moreover, a clear correlation between RNAP II degradation and in vivo pathogenicity in mice was observed, indicating that the

  12. Advances in influenza vaccination

    PubMed Central

    Reperant, Leslie A.; Rimmelzwaan, Guus F.

    2014-01-01

    Influenza virus infections yearly cause high morbidity and mortality burdens in humans, and the development of a new influenza pandemic continues to threaten mankind as a Damoclean sword. Influenza vaccines have been produced by using egg-based virus growth and passaging techniques that were developed more than 60 years ago, following the identification of influenza A virus as an etiological agent of seasonal influenza. These vaccines aimed mainly at eliciting neutralizing antibodies targeting antigenically variable regions of the hemagglutinin (HA) protein, which requires regular updates to match circulating seasonal influenza A and B virus strains. Given the relatively limited protection induced by current seasonal influenza vaccines, a more universal influenza vaccine that would protect against more—if not all—influenza viruses is among the largest unmet medical needs of the 21st century. New insights into correlates of protection from influenza and into broad B- and T-cell protective anti-influenza immune responses offer promising avenues for innovative vaccine development as well as manufacturing strategies or platforms, leading to the development of a new generation of vaccines. These aim at the rapid and massive production of influenza vaccines that provide broad protective and long-lasting immunity. Recent advances in influenza vaccine research demonstrate the feasibility of a wide range of approaches and call for the initiation of preclinical proof-of-principle studies followed by clinical trials in humans. PMID:24991424

  13. Efficacy of a non-updated, Matrix-C-based equine influenza subunit-tetanus vaccine following Florida sublineage clade 2 challenge.

    PubMed

    Pouwels, H G W; Van de Zande, S M A; Horspool, L J I; Hoeijmakers, M J H

    2014-06-21

    Assessing the ability of current equine influenza vaccines to provide cross-protection against emerging strains is important. Horses not vaccinated previously and seronegative for equine influenza based on haemagglutination inhibition (HI) assay were assigned at random to vaccinated (n=7) or non-vaccinated (control, n=5) groups. Vaccination was performed twice four weeks apart with a 1 ml influenza subunit (A/eq/Prague/1/56, A/eq/Newmarket/1/93, A/eq/Newmarket/2/93), tetanus toxoid vaccine with Matrix-C adjuvant (EquilisPrequenza Te). All the horses were challenged individually by aerosol with A/eq/Richmond/1/07 three weeks after the second vaccination. Rectal temperature, clinical signs, serology and virus excretion were monitored for 14 days after challenge. There was no pain at the injection site or increases in rectal temperature following vaccination. Increases in rectal temperature and characteristic clinical signs were recorded in the control horses. Clinical signs were minimal in vaccinated horses. Clinical (P=0.0345) and total clinical scores (P=0.0180) were significantly lower in the vaccinated than in the control horses. Vaccination had a significant effect on indicators of viraemia - the extent (P=0.0006) and duration (P=<0.0001) of virus excretion and the total amount of virus excreted (AUC, P=0.0006). Vaccination also had a significant effect (P=0.0017) on whether a horse was positive or negative for virus excretion during the study. Further research is needed to fully understand the specific properties of this vaccine that may contribute to its cross-protective capacity. PMID:24795071

  14. Subunit influenza vaccine candidate based on CD154 fused to HAH5 increases the antibody titers and cellular immune response in chickens.

    PubMed

    Pose, Alaín González; Gómez, Julia Noda; Sánchez, Alina Venereo; Redondo, Armando Vega; Rodríguez, Elsa Rodríguez; Seguí, Raquel Montesino; Ramos, Ernesto Manuel González; Moltó, María Pilar Rodríguez; Rodríguez, Elaine Santana; Cordero, Liliam Rios; Mallón, Alina Rodríguez; Nordelo, Carlos Borroto

    2011-09-28

    World Health Organization has a great concern about the spreading of avian influenza virus H5N1. To counteract its massive spread, poultry vaccination is highly recommended together with biosecurity measures. In our study, a recombinant vaccine candidate based on the fusion of extracellular segments of hemagglutinin (HA) H5 of avian influenza virus and chicken CD154 (HACD) is tested with the aim of enhancing humoral and cellular immune responses in chickens. Protein expression was carried out by transducing several mammalian cell lines with recombinant adenoviral vectors. HACD purification was assessed by three distinct purification protocols: immunoaffinity chromatography by elution at acidic pH or with a chaotropic agent and size exclusion chromatography. Humoral and cellular immune responses were measured using the hemagglutination inhibition assay and the semiquantitative real time PCR, respectively. The results showed that humoral response against HACD was significantly higher than the obtained with HA alone after booster (P<0.01, P<0.05). From HACD molecules purified by distinct protocols, only the obtained by size exclusion chromatography generated hemagglutinationin-inhibition activity. IFN-γ levels indicated that cellular immune response was significantly higher with HACD, in its pure or impure form, compared to its counterpart HA (P<0.01). These data demonstrate that HACD is able to significantly enhance humoral and cellular immune responses against HA antigen, which make this fusion protein a promising subunit vaccine candidate against H5N1 virus outbreaks. PMID:21680114

  15. Intranasal immunization with live recombinant Lactococcus lactis combined with heat-labile toxin B subunit protects chickens from highly pathogenic avian influenza H5N1 virus.

    PubMed

    Lei, Han; Peng, Xiaojue; Shu, Handing; Zhao, Daxian

    2015-01-01

    Development of safe and effective vaccines to prevent highly pathogenic avian influenza H5N1 virus infection is a challenging goal. Lactococcus lactis (L. lactis) is an ideal delivery vector for vaccine development, and it has been shown previously that oral immunization of encapsulated secretory L. lactis-hemagglutinin (HA) could provide complete protection against homologous H5N1 virus challenge in the mice model. While intranasal immunization is an appealing approach, it is now reported that secretory L. lactis-HA combined with mucosal adjuvant heat-labile toxin B subunit (LTB) could provide protective immunity in the chicken model. As compared to intranasal immunization with L. lactis-HA alone, L. lactis-HA combined with LTB (L. lactis-HA + LTB) could elicit robust neutralizing antibody responses and mucosal IgA responses, as well as strong cellular immune responses in the vaccinated chickens. Importantly, intranasal immunization with L. lactis-HA + LTB could provide 100% protection against H5N1 virus challenge. Taken together, these results suggest that intranasal immunization with L. lactis-HA + LTB can be considered as an effective approach for preventing and controlling infection of H5N1 virus in poultry during an avian influenza A/H5N1 pandemic. PMID:24861477

  16. Mapping the domain structure of the influenza A virus polymerase acidic protein (PA) and its interaction with the basic protein 1 (PB1) subunit

    SciTech Connect

    Guu, Tom S.Y.; Dong Liping; Wittung-Stafshede, Pernilla; Tao, Yizhi J.

    2008-09-15

    The influenza A virus polymerase consists of three subunits (PA, PB1, and PB2) necessary for viral RNA synthesis. The heterotrimeric polymerase complex forms through PA interacting with PB1 and PB1 interacting with PB2. PA has been shown to play critical roles in the assembly, catalysis, and nuclear localization of the polymerase. To probe the structure of PA, we isolated recombinant PA from insect cells. Limited proteolysis revealed that PA contained two domains connected by a 20-residue linker (residues 257-276). Far-UV circular dichroism established that the two domains folded into a mixed {alpha}/{beta} structure when separately expressed. In vitro pull-down assays showed that neither individually nor cooperatively expressed PA domains, without the linker, could assure PA-PB1 interaction. Protease treatment of PA-PB1 complex indicated that its PA subunit was significantly more stable than free PA, suggesting that the linker is protected and it constitutes an essential component of the PA-PB1 interface.

  17. Two Distinctive Binding Modes of Endonuclease Inhibitors to the N-Terminal Region of Influenza Virus Polymerase Acidic Subunit.

    PubMed

    Fudo, Satoshi; Yamamoto, Norio; Nukaga, Michiyoshi; Odagiri, Takato; Tashiro, Masato; Hoshino, Tyuji

    2016-05-10

    Influenza viruses are global threat to humans, and the development of new antiviral agents are still demanded to prepare for pandemics and to overcome the emerging resistance to the current drugs. Influenza polymerase acidic protein N-terminal domain (PAN) has endonuclease activity and is one of the appropriate targets for novel antiviral agents. First, we performed X-ray cocrystal analysis on the complex structures of PAN with two endonuclease inhibitors. The protein crystallization and the inhibitor soaking were done at pH 5.8. The binding modes of the two inhibitors were different from a common binding mode previously reported for the other influenza virus endonuclease inhibitors. We additionally clarified the complex structures of PAN with the same two endonuclease inhibitors at pH 7.0. In one of the crystal structures, an additional inhibitor molecule, which chelated to the two metal ions in the active site, was observed. On the basis of the crystal structures at pH 7.0, we carried out 100 ns molecular dynamics (MD) simulations for both of the complexes. The analysis of simulation results suggested that the binding mode of each inhibitor to PAN was stable in spite of the partial deviation of the simulation structure from the crystal one. Furthermore, crystal structure analysis and MD simulation were performed for PAN in complex with an inhibitor, which was already reported to have a high compound potency for comparison. The findings on the presence of multiple binding sites at around the PAN substrate-binding pocket will provide a hint for enhancing the binding affinity of inhibitors. PMID:27088785

  18. Whole inactivated virus influenza vaccine is superior to subunit vaccine in inducing immune responses and secretion of proinflammatory cytokines by DCs

    PubMed Central

    Geeraedts, Felix; Bungener, Laura; Pool, Judith; Ter Veer, Wouter; Wilschut, Jan; Huckriede, Anke

    2008-01-01

    Background  For protection against (re‐)infection by influenza virus not only the magnitude of the immune response but also its quality in terms of antibody subclass and T helper profile is important. Information about the type of immune response elicited by vaccination is therefore urgently needed. Objectives  The aim of the study was to evaluate in detail the immune response elicited by three current influenza vaccine formulations and to shed light on vaccine characteristics which determine this response. Methods  Mice were immunized with whole inactivated virus (WIV), virosomes (VS) or subunit vaccine (SU). Following subsequent infection with live virus, serum antibody titers and Th cell responses were measured. The effects of the vaccines on cytokine production by conventional and plasmacytoid dendritic cells were investigated in vitro. Results and conclusions  In Balb/c mice (Th2 prone) as well as in C57Bl/6 mice (Th1 prone), WIV induced consistently higher hemagglutination‐inhibition titers and virus‐neutralizing antibody titers than VS or SU. In contrast to VS and SU, WIV stimulated the production of the antibody subclasses IgG2a (Balb/c) and IgG2c (C57BL/6), considered to be particularly important for viral clearance, and activation of IFN‐γ‐producing T cells. Similar to live virus, WIV stimulated the production of proinflammatory cytokines by conventional dendritic cells and IFN‐α by plasmacytoid cells, while VS and SU had little effect on cytokine synthesis by either cell type. We conclude that vaccination with WIV in contrast to VS or SU results in the desired Th1 response presumably by induction of type I interferon and other proinflammatory cytokines. PMID:19453471

  19. Adjuvant Effect of Cationic Liposomes for Subunit Influenza Vaccine: Influence of Antigen Loading Method, Cholesterol and Immune Modulators

    PubMed Central

    Barnier-Quer, Christophe; Elsharkawy, Abdelrahman; Romeijn, Stefan; Kros, Alexander; Jiskoot, Wim

    2013-01-01

    Cationic liposomes are potential adjuvants for influenza vaccines. In a previous study we reported that among a panel of cationic liposomes loaded with influenza hemagglutinin (HA), DC-Chol:DPPC (1:1 molar ratio) liposomes induced the strongest immune response. However, it is not clear whether the cholesterol (Chol) backbone or the tertiary amine head group of DC-Chol was responsible for this. Therefore, in the present work we studied the influence of Chol in the lipid bilayer of cationic liposomes. Moreover, we investigated the effect of the HA loading method (adsorption versus encapsulation) and the encapsulation of immune modulators in DC-Chol liposomes on the immunogenicity of HA. Liposomes consisting of a neutral lipid (DPPC or Chol) and a cationic compound (DC-Chol, DDA, or eDPPC) were produced by film hydration-extrusion with/without an encapsulated immune modulator (CpG or imiquimod). The liposomes generally showed comparable size distribution, zeta potential and HA loading. In vitro studies with monocyte-derived human dendritic cells and immunization studies in C57Bl/6 mice showed that: (1) liposome-adsorbed HA is more immunogenic than encapsulated HA; (2) the incorporation of Chol in the bilayer of cationic liposomes enhances their adjuvant effect; and (3) CpG loaded liposomes are more efficient at enhancing HA-specific humoral responses than plain liposomes or Alhydrogel. PMID:24300513

  20. A Novel Functional Site in the PB2 Subunit of Influenza A Virus Essential for Acetyl-CoA Interaction, RNA Polymerase Activity, and Viral Replication*

    PubMed Central

    Hatakeyama, Dai; Shoji, Masaki; Yamayoshi, Seiya; Hirota, Takenori; Nagae, Monami; Yanagisawa, Shin; Nakano, Masahiro; Ohmi, Naho; Noda, Takeshi; Kawaoka, Yoshihiro; Kuzuhara, Takashi

    2014-01-01

    The PA, PB1, and PB2 subunits, components of the RNA-dependent RNA polymerase of influenza A virus, are essential for viral transcription and replication. The PB2 subunit binds to the host RNA cap (7-methylguanosine triphosphate (m7GTP)) and supports the endonuclease activity of PA to “snatch” the cap from host pre-mRNAs. However, the structure of PB2 is not fully understood, and the functional sites remain unknown. In this study, we describe a novel Val/Arg/Gly (VRG) site in the PB2 cap-binding domain, which is involved in interaction with acetyl-CoA found in eukaryotic histone acetyltransferases (HATs). In vitro experiments revealed that the recombinant PB2 cap-binding domain that includes the VRG site interacts with acetyl-CoA; moreover, it was found that this interaction could be blocked by CoA and various HAT inhibitors. Interestingly, m7GTP also inhibited this interaction, suggesting that the same active pocket is capable of interacting with acetyl-CoA and m7GTP. To elucidate the importance of the VRG site on PB2 function and viral replication, we constructed a PB2 recombinant protein and recombinant viruses including several patterns of amino acid mutations in the VRG site. Substitutions of the valine and arginine residues or of all 3 residues of the VRG site to alanine significantly reduced the binding ability of PB2 to acetyl-CoA and its RNA polymerase activity. Recombinant viruses containing the same mutations could not be replicated in cultured cells. These results indicate that the PB2 VRG sequence is a functional site that is essential for acetyl-CoA interaction, RNA polymerase activity, and viral replication. PMID:25063805

  1. Hydrophobic photolabeling identifies BHA2 as the subunit mediating the interaction of bromelain-solubilized influenza virus hemagglutinin with liposomes at low pH

    SciTech Connect

    Harter, C.; Baechi, T.S.; Semenza, G.; Brunner, J.

    1988-03-22

    To investigate the molecular basis of the low-pH-mediated interaction of the bromelain-solubilized ectodomain of influenza virus hemagglutinin (BHA) with membranes, we have photolabeled BHA in the presence of liposomes with the two carbene-generating, membrane-directed reagents 3-(trifluoromethyl)-3-(m-(/sup 125/I)iodophenyl)diazirine ((/sup 125/I)TID) and a new analogue of a phospholipid, 1-palmitoyl-2-(11-(4-(3-(trifluoromethyl)diazirinyl)phenyl)(2-/sup 3/H) undecanoyl)-sn-glycero-3-phosphocholine ((/sup 3/H)-PTPC/11). With the latter reagent, BHA was labeled in a strictly pH-dependent manner, i.e., at pH 5 only, whereas with (/sup 125/I)TID, labeling was seen also at pH 7. In all experiments, the label was selectively incorporated into the BHA2 polypeptide, demonstrating that the interaction of BHA with membranes is mediated through this subunit, possibly via its hydrophobic N-terminal segment. Similar experiments with a number of other water-soluble proteins (ovalbumin, carbonic anhydrase, alpha-lactalbumin, trypsin, and soybean trypsin inhibitor) indicate that the ability to interact with liposomes at low pH is not a property specific for BHA but is observed with other, perhaps most, proteins.

  2. Shelf-stable egg-based products processed by high pressure thermal sterilization

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Producing a thermally sterilized egg-based product with increased shelf life without losing the sensory and nutritional properties of the freshly prepared product is challenging. Until recently, all commercial shelf-stable egg-based products were sterilized using conventional thermal processing; how...

  3. Replication-competent influenza A virus that encodes a split-green fluorescent protein-tagged PB2 polymerase subunit allows live-cell imaging of the virus life cycle.

    PubMed

    Avilov, Sergiy V; Moisy, Dorothée; Munier, Sandie; Schraidt, Oliver; Naffakh, Nadia; Cusack, Stephen

    2012-02-01

    Studies on the intracellular trafficking of influenza virus ribonucleoproteins are currently limited by the lack of a method enabling their visualization during infection in single cells. This is largely due to the difficulty of encoding fluorescent fusion proteins within the viral genome. To circumvent this limitation, we used the split-green fluorescent protein (split-GFP) system (S. Cabantous, T. C. Terwilliger, and G. S. Waldo, Nat. Biotechnol. 23:102-107, 2005) to produce a quasi-wild-type recombinant A/WSN/33/influenza virus which allows expression of individually fluorescent PB2 polymerase subunits in infected cells. The viral PB2 proteins were fused to the 16 C-terminal amino acids of the GFP, whereas the large transcomplementing GFP fragment was supplied by transient or stable expression in cultured cells that were permissive to infection. This system was used to characterize the intranuclear dynamics of PB2 by fluorescence correlation spectroscopy and to visualize the trafficking of viral ribonucleoproteins (vRNPs) by dynamic light microscopy in live infected cells. Following nuclear export, vRNPs showed a transient pericentriolar accumulation and intermittent rapid (∼1 μm/s), directional movements in the cytoplasm, dependent on both microtubules and actin filaments. Our data establish the potential of split-GFP-based recombinant viruses for the tracking of viral proteins during a quasi-wild-type infection. This new virus, or adaptations of it, will be of use in elucidating many aspects of influenza virus host cell interactions as well as in screening for new antiviral compounds. Furthermore, the existence of cell lines stably expressing the complementing GFP fragment will facilitate applications to many other viral and nonviral systems. PMID:22114331

  4. Advances in novel influenza vaccines: a patent review.

    PubMed

    Song, Jae-Min

    2016-06-01

    The threat of a major human influenza pandemic such as the avian H5N1 or the 2009 new H1N1 has emphasized the need for effective prevention strategies to combat these pathogens. Although egg based influenza vaccines have been well established for a long time, it remains an ongoing public health need to develop alternative production methods that ensures improved safety, efficacy, and ease of administration compared with conventional influenza vaccines. This article is intended to cover some of the recent advances and related patents on the development of influenza vaccines including live attenuated, cell based, genomic and synthetic peptide vaccines. PMID:27225456

  5. Egg-adaptive mutations in H3N2v vaccine virus enhance egg-based production without loss of antigenicity or immunogenicity.

    PubMed

    Barman, Subrata; Franks, John; Turner, Jasmine C; Yoon, Sun-Woo; Webster, Robert G; Webby, Richard J

    2015-06-22

    The recently detected zoonotic H3N2 variant influenza A (H3N2v) viruses have caused 343 documented cases of human infection linked to contact with swine. An effective vaccine is needed for these viruses, which may acquire transmissibility among humans. However, viruses isolated from human cases do not replicate well in embryonated chicken eggs, posing an obstacle to egg-based vaccine production. To address this issue, we sought to identify egg-adaptive mutations in surface proteins that increase the yield of candidate vaccine viruses (CVVs) in eggs while preserving their immunizing effectiveness. After serial passage of a representative H3N2v isolate (A/Indiana/08/2011), we identified several egg-adaptive combinations of HA mutations and assessed the egg-based replication, antigenicity, and immunogenicity of A/Puerto Rico/8/34 (H1N1, PR8)-based 6+2 reverse genetics CVVs carrying these mutations. Here we demonstrate that the respective combined HA substitutions G1861V+N2461K, N1651K+G1861V, T1281N+N1651K+R762G, and T1281N+N1651K+I102M, all identified after egg passage, enhanced the replication of the CVVs in eggs without substantially affecting their antigenicity or immunogenicity. The mutations were stable, and the mutant viruses acquired no additional substitutions during six subsequent egg passages. We found two crucial mutations, G186V, which was previously defined, and N246K, which in combination improved virus yield in eggs without significantly impacting antigenicity or immunogenicity. This combination of egg-adaptive mutations appears to most effectively generate high egg-based yields of influenza A/Indiana/08/2011-like CVVs. PMID:25999284

  6. Antibodies against the majority subunit of Type IV pili disperse nontypeable Haemophilus influenzae biofilms in a LuxS-dependent manner and confer therapeutic resolution of experimental otitis media

    PubMed Central

    Novotny, Laura A.; Jurcisek, Joseph A.; Ward, Michael O.; Jordan, Zachary B.; Goodman, Steven D.; Bakaletz, Lauren O.

    2015-01-01

    Summary Despite resulting in a similar overall outcome, unlike antibodies directed against the DNABII protein, integration host factor (IHF), which induce catastrophic structural collapse of biofilms formed by nontypeable Haemophilus influenzae (NTHI), those directed against a recombinant soluble form of PilA [the majority subunit of Type IV pili (Tfp) produced by NTHI], mediated gradual ‘top-down’ dispersal of NTHI from biofilms. This dispersal occurred via a mechanism that was dependent upon expression of both PilA (and by inference, Tfp) and production of AI-2 quorum signaling molecules by LuxS. The addition of rsPilA to a biofilm-targeted therapeutic vaccine formulation comprised of IHF plus the powerful adjuvant dmLT, and delivered via a non-invasive transcutaneous immunization route, induced an immune response that targeted two important determinants essential for biofilm formation by NTHI. This resulted in significantly earlier eradication of NTHI from both planktonic and adherent populations in the middle ear, disruption of mucosal biofilms already resident within middle ears prior to immunization, and rapid resolution of signs of disease in an animal model of experimental otitis media. These data support continued development of this novel combinatorial immunization approach for resolution and/or prevention of multiple diseases of the respiratory tract caused by NTHI. PMID:25597921

  7. Antibodies against the majority subunit of type IV Pili disperse nontypeable Haemophilus influenzae biofilms in a LuxS-dependent manner and confer therapeutic resolution of experimental otitis media.

    PubMed

    Novotny, Laura A; Jurcisek, Joseph A; Ward, Michael O; Jordan, Zachary B; Goodman, Steven D; Bakaletz, Lauren O

    2015-04-01

    Despite resulting in a similar overall outcome, unlike antibodies directed against the DNABII protein, integration host factor (IHF), which induce catastrophic structural collapse of biofilms formed by nontypeable Haemophilus influenzae (NTHI), those directed against a recombinant soluble form of PilA [the majority subunit of Type IV pili (Tfp) produced by NTHI], mediated gradual 'top-down' dispersal of NTHI from biofilms. This dispersal occurred via a mechanism that was dependent upon expression of both PilA (and by inference, Tfp) and production of AI-2 quorum signaling molecules by LuxS. The addition of rsPilA to a biofilm-targeted therapeutic vaccine formulation comprised of IHF plus the powerful adjuvant dmLT and delivered via a noninvasive transcutaneous immunization route induced an immune response that targeted two important determinants essential for biofilm formation by NTHI. This resulted in significantly earlier eradication of NTHI from both planktonic and adherent populations in the middle ear, disruption of mucosal biofilms already resident within middle ears prior to immunization and rapid resolution of signs of disease in an animal model of experimental otitis media. These data support continued development of this novel combinatorial immunization approach for resolution and/or prevention of multiple diseases of the respiratory tract caused by NTHI. PMID:25597921

  8. Enhanced Immunogenicity of Stabilized Trimeric Soluble Influenza Hemagglutinin

    PubMed Central

    Weldon, William C.; Wang, Bao-Zhong; Martin, Maria P.; Koutsonanos, Dimitrios G.; Skountzou, Ioanna; Compans, Richard W.

    2010-01-01

    Background The recent swine-origin H1N1 pandemic illustrates the need to develop improved procedures for rapid production of influenza vaccines. One alternative to the current egg-based manufacture of influenza vaccine is to produce a hemagglutinin (HA) subunit vaccine using a recombinant expression system with the potential for high protein yields, ease of cloning new antigenic variants, and an established safety record in humans. Methodology/Principal Findings We generated a soluble HA (sHA), derived from the H3N2 virus A/Aichi/2/68, modified at the C-terminus with a GCN4pII trimerization repeat to stabilize the native trimeric structure of HA. When expressed in the baculovirus system, the modified sHA formed native trimers. In contrast, the unmodified sHA was found to present epitopes recognized by a low-pH conformation specific monoclonal antibody. We found that mice primed and boosted with 3 µg of trimeric sHA in the absence of adjuvants had significantly higher IgG and HAI titers than mice that received the unmodified sHA. This correlated with an increased survival and reduced body weight loss following lethal challenge with mouse-adapted A/Aichi/2/68 virus. In addition, mice receiving a single vaccination of the trimeric sHA in the absence of adjuvants had improved survival and body weight loss compared to mice vaccinated with the unmodified sHA. Conclusions/Significance Our data indicate that the recombinant trimeric sHA presents native trimeric epitopes while the unmodified sHA presents epitopes not exposed in the native HA molecule. The epitopes presented in the unmodified sHA constitute a “silent face” which may skew the antibody response to epitopes not accessible in live virus at neutral pH. The results demonstrate that the trimeric sHA is a more effective influenza vaccine candidate and emphasize the importance of structure-based antigen design in improving recombinant HA vaccines. PMID:20824188

  9. Flu (Influenza)

    MedlinePlus

    ... Skip Content Marketing Share this: Main Content Area Flu (Influenza) Overview Influenza, or flu, is a respiratory infection ... the flu and its complications every year. Seasonal Flu Seasonal flu refers to the flu outbreaks that ...

  10. Avian influenza

    MedlinePlus

    Bird flu; H5N1; H5N2; H5N8; H7N9; Avian influenza A (HPAI) H5 ... The first avian influenza in humans was reported in Hong Kong in 1997. It was called avian influenza (H5N1). The outbreak was linked ...

  11. Development of pandemic influenza vaccine production capacity in Viet Nam.

    PubMed

    Hoa, L K; Hiep, L V; Be, L V

    2011-07-01

    The Institute of Vaccines and Medical Biologicals (IVAC), a state-owned vaccine manufacturer, initiated research into avian influenza vaccines in the early 1990 s in response to the threat of a highly pathogenic avian influenza pandemic. Successful results from laboratory studies on A(H5N1) influenza virus attracted seed funds and led to participation in the WHO technology transfer project to enhance influenza vaccine production in developing countries. IVAC's goal is to produce 500,000 doses of inactivated monovalent whole-virion influenza vaccine per year by 2012, and progressively increase capacity to more than 1 million doses to protect essential populations in Viet Nam in the event of an influenza pandemic. The WHO seed grants, supplemented by other international partner support, enabled IVAC to build in a very short time an influenza vaccine manufacturing plant under Good Manufacturing Practice and relevant biosafety standards, a waste treatment system and a dedicated chicken farm for high-quality eggs. Much of the equipment and instrumentation required for vaccine production has been installed and tested for functional operation. Staff have been trained on site and at specialized courses which provided comprehensive manuals on egg-based manufacturing processes and biosafety. Following process validation, clinical trials will start in 2011 and the first domestic influenza vaccine doses are expected in 2012. PMID:21684426

  12. Obesity-induced chronic inflammation is associated with the reduced efficacy of influenza vaccine

    PubMed Central

    Park, Hye-Lim; Shim, Seung-Hyun; Lee, Eun-Young; Cho, Whajung; Park, Sooho; Jeon, Hyun-Jung; Ahn, Sun-Young; Kim, Hun; Nam, Jae-Hwan

    2014-01-01

    The relationship between obesity and vaccine efficacy is a serious issue. Previous studies have shown that vaccine efficacy is lower in the obese than in the non-obese. Here, we examined the influence of obesity on the efficacy of influenza vaccination using high fat diet (HFD) and regular fat diet (RFD) mice that were immunized with 2 types of influenza virus vaccines—cell culture-based vaccines and egg-based vaccines. HFD mice showed lower levels of neutralizing antibody titers as compared with RFD mice. Moreover, HFD mice showed high levels of MCP-1 in serum and adipocytes, and low level of influenza virus-specific effector memory CD8+ T cells. After challenge with influenza virus, the lungs of HFD mice showed more severe inflammatory responses as compared with the lungs of RFD mice, even after vaccination. Taken together, our data suggested that the inflammatory condition in obesity may contribute to the suppressed efficacy of influenza vaccination. PMID:24614530

  13. [Influenza surveillance].

    PubMed

    Bednarska, Karolina; Hallmann-Szelińska, Ewelina; Kondratiuk, Katarzyna; Brydak, Lidia B

    2016-01-01

    Influenza surveillance was established in 1947. From this moment WHO (World Health Organization) has been coordinating international cooperation, with a goal of monitoring influenza virus activity, effective diagnostic of the circulating viruses and informing society about epidemics or pandemics, as well as about emergence of new subtypes of influenza virus type A. Influenza surveillance is an important task, because it enables people to prepare themselves for battle with the virus that is constantly mutating, what leads to circulation of new and often more virulent strains of influenza in human population. As vaccination is the most effective method of fighting the virus, one of the major tasks of GISRS is developing an optimal antigenic composition of the vaccine for the current epidemic season. European Influenza Surveillance Network (EISN) has also developed over the years. EISN is running integrated epidemiological and virological influenza surveillance, to provide appropriate data to public health experts in member countries, to enable them undertaking relevant activities based on the current information about influenza activity. In close cooperation with GISRS and EISN are National Influenza Centres--national institutions designated by the Ministry of Health in each country. PMID:27117107

  14. New technologies for influenza vaccines.

    PubMed

    Dormitzer, Philip R; Tsai, Theodore F; Del Giudice, Giuseppe

    2012-01-01

    Influenza vaccine preparations have been administered to humans since the late 1930s, and the diversity of approaches in licensed trivalent seasonal or monovalent pandemic products is unparalleled by vaccines against any other target. These approaches include inactivated whole virus vaccines, detergent or solvent "split" vaccines, subunit vaccines, live attenuated vaccines, adjuvanted vaccines, intramuscular vaccines, intradermal vaccines, intranasal vaccines, egg-produced vaccines and mammalian cell culture-produced vaccines. The challenges of influenza immunization, including multiple co-circulating strains, antigenic change over time, a broad age spectrum of disease, and the threat of pandemics, continue to drive the development of new approaches. This review describes some of the new approaches to influenza immunization that are the subjects of active research and development. PMID:22251994

  15. Development of Stable Influenza Vaccine Powder Formulations: Challenges and Possibilities

    PubMed Central

    Amorij, J-P.; Huckriede, A.; Wilschut, J.; Frijlink, H. W.

    2008-01-01

    Influenza vaccination represents the cornerstone of influenza prevention. However, today all influenza vaccines are formulated as liquids that are unstable at ambient temperatures and have to be stored and distributed under refrigeration. In order to stabilize influenza vaccines, they can be brought into the dry state using suitable excipients, stabilizers and drying processes. The resulting stable influenza vaccine powder is independent of cold-chain facilities. This can be attractive for the integration of the vaccine logistics with general drug distribution in Western as well as developing countries. In addition, a stockpile of stable vaccine formulations of potential vaccines against pandemic viruses can provide an immediate availability and simple distribution of vaccine in a pandemic outbreak. Finally, in the development of new needle-free dosage forms, dry and stable influenza vaccine powder formulations can facilitate new or improved targeting strategies for the vaccine compound. This review represents the current status of dry stable inactivated influenza vaccine development. Attention is given to the different influenza vaccine types (i.e. whole inactivated virus, split, subunit or virosomal vaccine), the rationale and need for stabilized influenza vaccines, drying methods by which influenza vaccines can be stabilized (i.e. lyophilization, spray drying, spray-freeze drying, vacuum drying or supercritical fluid drying), the current status of dry influenza vaccine development and the challenges for ultimate market introduction of a stable and effective dry-powder influenza vaccine. PMID:18338241

  16. Antibody Persistence in Adults Two Years after Vaccination with an H1N1 2009 Pandemic Influenza Virus-Like Particle Vaccine.

    PubMed

    Valero-Pacheco, Nuriban; Pérez-Toledo, Marisol; Villasís-Keever, Miguel Ángel; Núñez-Valencia, Adriana; Boscó-Gárate, Ilka; Lozano-Dubernard, Bernardo; Lara-Puente, Horacio; Espitia, Clara; Alpuche-Aranda, Celia; Bonifaz, Laura C; Arriaga-Pizano, Lourdes; Pastelin-Palacios, Rodolfo; Isibasi, Armando; López-Macías, Constantino

    2016-01-01

    The influenza virus is a human pathogen that causes epidemics every year, as well as potential pandemic outbreaks, as occurred in 2009. Vaccination has proven to be sufficient in the prevention and containment of viral spreading. In addition to the current egg-based vaccines, new and promising vaccine platforms, such as cell culture-derived vaccines that include virus-like particles (VLPs), have been developed. VLPs have been shown to be both safe and immunogenic against influenza infections. Although antibody persistence has been studied in traditional egg-based influenza vaccines, studies on antibody response durations induced by VLP influenza vaccines in humans are scarce. Here, we show that subjects vaccinated with an insect cell-derived VLP vaccine, in the midst of the 2009 H1N1 influenza pandemic outbreak in Mexico City, showed antibody persistence up to 24 months post-vaccination. Additionally, we found that subjects that reported being revaccinated with a subsequent inactivated influenza virus vaccine showed higher antibody titres to the pandemic influenza virus than those who were not revaccinated. These findings provide insights into the duration of the antibody responses elicited by an insect cell-derived pandemic influenza VLP vaccine and the possible effects of subsequent influenza vaccination on antibody persistence induced by this VLP vaccine in humans. PMID:26919288

  17. Antibody Persistence in Adults Two Years after Vaccination with an H1N1 2009 Pandemic Influenza Virus-Like Particle Vaccine

    PubMed Central

    Villasís-Keever, Miguel Ángel; Núñez-Valencia, Adriana; Boscó-Gárate, Ilka; Lozano-Dubernard, Bernardo; Lara-Puente, Horacio; Espitia, Clara; Alpuche-Aranda, Celia; Bonifaz, Laura C.; Arriaga-Pizano, Lourdes; Pastelin-Palacios, Rodolfo; Isibasi, Armando; López-Macías, Constantino

    2016-01-01

    The influenza virus is a human pathogen that causes epidemics every year, as well as potential pandemic outbreaks, as occurred in 2009. Vaccination has proven to be sufficient in the prevention and containment of viral spreading. In addition to the current egg-based vaccines, new and promising vaccine platforms, such as cell culture-derived vaccines that include virus-like particles (VLPs), have been developed. VLPs have been shown to be both safe and immunogenic against influenza infections. Although antibody persistence has been studied in traditional egg-based influenza vaccines, studies on antibody response durations induced by VLP influenza vaccines in humans are scarce. Here, we show that subjects vaccinated with an insect cell-derived VLP vaccine, in the midst of the 2009 H1N1 influenza pandemic outbreak in Mexico City, showed antibody persistence up to 24 months post-vaccination. Additionally, we found that subjects that reported being revaccinated with a subsequent inactivated influenza virus vaccine showed higher antibody titres to the pandemic influenza virus than those who were not revaccinated. These findings provide insights into the duration of the antibody responses elicited by an insect cell-derived pandemic influenza VLP vaccine and the possible effects of subsequent influenza vaccination on antibody persistence induced by this VLP vaccine in humans. PMID:26919288

  18. An international technology platform for influenza vaccines.

    PubMed

    Hendriks, Jan; Holleman, Marit; de Boer, Otto; de Jong, Patrick; Luytjes, Willem

    2011-07-01

    Since 2008, the World Health Organization has provided seed grants to 11 manufacturers in low- and middle-income countries to establish or improve their pandemic influenza vaccine production capacity. To facilitate this ambitious project, an influenza vaccine technology platform (or "hub") was established at the Netherlands Vaccine Institute for training and technology transfer to developing countries. During its first two years of operation, a robust and transferable monovalent pilot process for egg-based inactivated whole virus influenza A vaccine production was established under international Good Manufacturing Practice standards, as well as in-process and release assays. A course curriculum was designed, including a two-volume practical handbook on production and quality control. Four generic hands-on training courses were successfully realized for over 40 employees from 15 developing country manufacturers. Planned extensions to the curriculum include cell-culture based technology for viral vaccine production, split virion influenza production, and generic adjuvant formulation. We conclude that technology transfer through the hub model works well, significantly builds vaccine manufacturing capacity in developing countries, and thereby increases global and equitable access to vaccines of high public health relevance. PMID:21684431

  19. Avian influenza

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Avian influenza (AI) is a viral infection of birds that varies in severity from asymptomatic infections to mild respiratory and reproductive diseases to an acute, highly fatal systemic disease of chickens, turkeys, guinea fowls, and other avian species. Avian influenza viruses are divided into two ...

  20. Cause of Flu (Influenza)

    MedlinePlus

    ... Skip Content Marketing Share this: Main Content Area Flu (Influenza) Cause About the Flu Virus Influenza, or flu, is a respiratory infection ... the virus. Influenza A virus. Credit: CDC Where Influenza Comes From In nature, the flu virus is ...

  1. Avian Influenza

    MedlinePlus

    ... infectious viral disease of birds. Most avian influenza viruses do not infect humans; however some, such as ... often causing no apparent signs of illness. AI viruses can sometimes spread to domestic poultry and cause ...

  2. Evaluation of MDCK Cell-Derived Influenza H7N9 Vaccine Candidates in Ferrets

    PubMed Central

    Tseng, Yu-Fen; Weng, Tsai-Chuan; Lai, Chia-Chun; Lin, Jun-Yang; Chen, Po-Ling; Wang, Ya-Fang; Chao, Sin-Ru; Chang, Jui-Yuan; Hwang, Yi-Shiuh; Yeh, Chia-Tsui; Yu, Cheng-Ping; Chen, Yee-Chun; Su, Ih-Jen; Lee, Min-Shi

    2015-01-01

    Avian-origin influenza A (H7N9) viruses emerged as human pathogens in China in early 2013 and have killed >100 persons. Influenza vaccines are mainly manufactured using egg-based technology which could not meet the surging demand during influenza pandemics. In this study, we evaluated cell-based influenza H7N9 vaccines in ferrets. An egg-derived influenza H7N9 reassortant vaccine virus was adapted in MDCK cells. Influenza H7N9 whole virus vaccine antigen was manufactured using a microcarrier-based culture system. Immunogenicity and protection of the vaccine candidates with three different formulations (300μg aluminum hydroxide, 1.5μg HA, and 1.5μg HA plus 300μg aluminum hydroxide) were evaluated in ferrets. In ferrets receiving two doses of vaccination, geometric mean titers of hemagglutination (HA) inhibition and neutralizing antibodies were <10 and <40 for the control group (adjuvant only), 17 and 80 for the unadjuvanted (HA only) group, and 190 and 640 for the adjuvanted group (HA plus adjuvant), respectively. After challenge with wild-type influenza H7N9 viruses, virus titers in respiratory tracts of the adjuvanted group were significantly lower than that in the control, and unadjuvanted groups. MDCK cell-derived influenza H7N9 whole virus vaccine candidate is immunogenic and protective in ferrets and clinical development is highly warranted. PMID:25799397

  3. Current and Emerging Cell Culture Manufacturing Technologies for Influenza Vaccines

    PubMed Central

    Milián, Ernest; Kamen, Amine A.

    2015-01-01

    Annually, influenza virus infects millions of people worldwide. Vaccination programs against seasonal influenza infections require the production of hundreds of million doses within a very short period of time. The influenza vaccine is currently produced using a technology developed in the 1940s that relies on replicating the virus in embryonated hens' eggs. The monovalent viral preparation is inactivated and purified before being formulated in trivalent or tetravalent influenza vaccines. The production process has depended on a continuous supply of eggs. In the case of pandemic outbreaks, this mode of production might be problematic because of a possible drastic reduction in the egg supply and the low flexibility of the manufacturing process resulting in a lack of supply of the required vaccine doses in a timely fashion. Novel production systems using mammalian or insect cell cultures have emerged to overcome the limitations of the egg-based production system. These industrially well-established production systems have been primarily selected for a faster and more flexible response to pandemic threats. Here, we review the most important cell culture manufacturing processes that have been developed in recent years for mass production of influenza vaccines. PMID:25815321

  4. Current and emerging cell culture manufacturing technologies for influenza vaccines.

    PubMed

    Milián, Ernest; Kamen, Amine A

    2015-01-01

    Annually, influenza virus infects millions of people worldwide. Vaccination programs against seasonal influenza infections require the production of hundreds of million doses within a very short period of time. The influenza vaccine is currently produced using a technology developed in the 1940s that relies on replicating the virus in embryonated hens' eggs. The monovalent viral preparation is inactivated and purified before being formulated in trivalent or tetravalent influenza vaccines. The production process has depended on a continuous supply of eggs. In the case of pandemic outbreaks, this mode of production might be problematic because of a possible drastic reduction in the egg supply and the low flexibility of the manufacturing process resulting in a lack of supply of the required vaccine doses in a timely fashion. Novel production systems using mammalian or insect cell cultures have emerged to overcome the limitations of the egg-based production system. These industrially well-established production systems have been primarily selected for a faster and more flexible response to pandemic threats. Here, we review the most important cell culture manufacturing processes that have been developed in recent years for mass production of influenza vaccines. PMID:25815321

  5. Avian Influenza.

    PubMed

    Zeitlin, Gary Adam; Maslow, Melanie Jane

    2005-05-01

    The current epidemic of H5N1 highly pathogenic avian influenza in Southeast Asia raises serious concerns that genetic reassortment will result in the next influenza pandemic. There have been 164 confirmed cases of human infection with avian influenza since 1996. In 2004, there were 45 cases of human H5N1 in Vietnam and Thailand, with a mortality rate more than 70%. In addition to the potential public health hazard, the current zoonotic epidemic has caused severe economic losses. Efforts must be concentrated on early detection of bird outbreaks with aggressive culling, quarantining, and disinfection. To prepare for and prevent an increase in human cases, it is essential to improve detection methods and stockpile effective antivirals. Novel therapeutic modalities, including short-interfering RNAs and new vaccine strategies that use plasmid-based genetic systems, offer promise should a pandemic occur. PMID:15847721

  6. Avian influenza.

    PubMed

    Zeitlin, Gary A; Maslow, Melanie J

    2006-03-01

    The current epidemic of H5N1 highly pathogenic avian influenza in Southeast Asia raises serious concerns that genetic reassortment will result in the next influenza pandemic. There have been 164 confirmed cases of human infection with avian influenza since 1996. In 2004 alone, there were 45 cases of human H5N1 in Vietnam and Thailand, with a mortality rate over 70%. In addition to the potential public health hazard, the current zoonotic epidemic has caused severe economic losses. Efforts must be concentrated on early detection of bird outbreaks with aggressive culling, quarantines, and disinfection. To prepare for and prevent increased human cases, it is essential to improve detection methods and stockpile effective antivirals. Novel therapeutic modalities, including short, interfering RNAs and new vaccine strategies that use plasmid-based genetic systems offer promise, should a pandemic occur. PMID:16566867

  7. Immunogenicity of Virus Like Particle Forming Baculoviral DNA Vaccine against Pandemic Influenza H1N1

    PubMed Central

    Gwon, Yong-Dae; Kim, Sehyun; Cho, Yeondong; Heo, Yoonki; Cho, Hansam; Park, Kihoon; Lee, Hee-Jung; Choi, Jiwon; Poo, Haryoung; Kim, Young Bong

    2016-01-01

    An outbreak of influenza H1N1 in 2009, representing the first influenza pandemic of the 21st century, was transmitted to over a million individuals and claimed 18,449 lives. The current status in many countries is to prepare influenza vaccine using cell-based or egg-based killed vaccine. However, traditional influenza vaccine platforms have several limitations. To overcome these limitations, many researchers have tried various approaches to develop alternative production platforms. One of the alternative approach, we reported the efficacy of influenza HA vaccination using a baculoviral DNA vaccine (AcHERV-HA). However, the immune response elicited by the AcHERV-HA vaccine, which only targets the HA antigen, was lower than that of the commercial killed vaccine. To overcome the limitations of this previous vaccine, we constructed a human endogenous retrovirus (HERV) envelope-coated, baculovirus-based, virus-like-particle (VLP)–forming DNA vaccine (termed AcHERV-VLP) against pandemic influenza A/California/04/2009 (pH1N1). BALB/c mice immunized with AcHERV-VLP (1×107 FFU AcHERV-VLP, i.m.) and compared with mice immunized with the killed vaccine or mice immunized with AcHERV-HA. As a result, AcHERV-VLP immunization produced a greater humoral immune response and exhibited neutralizing activity with an intrasubgroup H1 strain (PR8), elicited neutralizing antibody production, a high level of interferon-γ secretion in splenocytes, and diminished virus shedding in the lung after challenge with a lethal dose of influenza virus. In conclusion, VLP-forming baculovirus DNA vaccine could be a potential vaccine candidate capable of efficiently delivering DNA to the vaccinee and VLP forming DNA eliciting stronger immunogenicity than egg-based killed vaccines. PMID:27149064

  8. Immunogenicity of Virus Like Particle Forming Baculoviral DNA Vaccine against Pandemic Influenza H1N1.

    PubMed

    Gwon, Yong-Dae; Kim, Sehyun; Cho, Yeondong; Heo, Yoonki; Cho, Hansam; Park, Kihoon; Lee, Hee-Jung; Choi, Jiwon; Poo, Haryoung; Kim, Young Bong

    2016-01-01

    An outbreak of influenza H1N1 in 2009, representing the first influenza pandemic of the 21st century, was transmitted to over a million individuals and claimed 18,449 lives. The current status in many countries is to prepare influenza vaccine using cell-based or egg-based killed vaccine. However, traditional influenza vaccine platforms have several limitations. To overcome these limitations, many researchers have tried various approaches to develop alternative production platforms. One of the alternative approach, we reported the efficacy of influenza HA vaccination using a baculoviral DNA vaccine (AcHERV-HA). However, the immune response elicited by the AcHERV-HA vaccine, which only targets the HA antigen, was lower than that of the commercial killed vaccine. To overcome the limitations of this previous vaccine, we constructed a human endogenous retrovirus (HERV) envelope-coated, baculovirus-based, virus-like-particle (VLP)-forming DNA vaccine (termed AcHERV-VLP) against pandemic influenza A/California/04/2009 (pH1N1). BALB/c mice immunized with AcHERV-VLP (1×107 FFU AcHERV-VLP, i.m.) and compared with mice immunized with the killed vaccine or mice immunized with AcHERV-HA. As a result, AcHERV-VLP immunization produced a greater humoral immune response and exhibited neutralizing activity with an intrasubgroup H1 strain (PR8), elicited neutralizing antibody production, a high level of interferon-γ secretion in splenocytes, and diminished virus shedding in the lung after challenge with a lethal dose of influenza virus. In conclusion, VLP-forming baculovirus DNA vaccine could be a potential vaccine candidate capable of efficiently delivering DNA to the vaccinee and VLP forming DNA eliciting stronger immunogenicity than egg-based killed vaccines. PMID:27149064

  9. Avian influenza

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Avian influenza (AI) viruses infect domestic poultry and wild birds. In domestic poultry, AI viruses are typically of low pathogenicity (LP) causing subclinical infections, respiratory disease or drops in egg production. However, a few AI viruses cause severe systemic disease with high mortality; i....

  10. AVIAN INFLUENZA

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Avian Influenza (AI) viruses infect domestic poultry and wild birds. In domestic poultry, AI viruses are typically of low pathogenicity (LP) causing subclinical infections, respiratory disease or drops in egg production. However, a few AI viruses cause severe systemic disease with high mortality; ...

  11. Influenza Photos

    MedlinePlus

    ... Forces Institute of Pathology, Washington, D.C., Image Smith 18 "Convalescing, 1918 influenza epidemic" www.vaccineinformation.org/ ... Forces Institute of Pathology, Washington, D.C., Image Smith 3 About • Contact • A-Z Index • Site Map • ...

  12. Avian influenza

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The natural host for avian influenza virus (AIV) is in wild birds, including ducks, gulls, and shorebirds, where the virus causes primarily an enteric infection with little disease. However, AIV can infect a wide variety of host species, and with a certain level of adaptation for the aberrant host ...

  13. Avian Influenza Virus and DIVA Strategies.

    PubMed

    Hasan, Noor Haliza; Ignjatovic, Jagoda; Peaston, Anne; Hemmatzadeh, Farhid

    2016-05-01

    Vaccination is becoming a more acceptable option in the effort to eradicate avian influenza viruses (AIV) from commercial poultry, especially in countries where AIV is endemic. The main concern surrounding this option has been the inability of the conventional serological tests to differentiate antibodies produced due to vaccination from antibodies produced in response to virus infection. In attempts to address this issue, at least six strategies have been formulated, aiming to differentiate infected from vaccinated animals (DIVA), namely (i) sentinel birds, (ii) subunit vaccine, (iii) heterologous neuraminidase (NA), (iv) nonstructural 1 (NS1) protein, (v) matrix 2 ectodomain (M2e) protein, and (vi) haemagglutinin subunit 2 (HA2) glycoprotein. This short review briefly discusses the strengths and limitations of these DIVA strategies, together with the feasibility and practicality of the options as a part of the surveillance program directed toward the eventual eradication of AIV from poultry in countries where highly pathogenic avian influenza is endemic. PMID:26900835

  14. The adjuvanted influenza vaccines with novel adjuvants: experience with the MF59-adjuvanted vaccine.

    PubMed

    Podda, A

    2001-03-21

    Elderly people and subjects with underlying chronic diseases are at increased risk for influenza and related complications. Conventional influenza vaccines provide only limited protection in the elderly population. In order to enhance the immune response to influenza vaccines, several adjuvants have been evaluated. Among these, an oil in water adjuvant emulsion containing squalene, MF59, has been combined with subunit influenza antigens and tested in clinical trials in comparison with non-adjuvanted conventional vaccines. Data from a clinical database of over 10000 elderly subjects immunised with this adjuvanted vaccine (Fluad, Chiron Vaccines, Siena, Italy) demonstrate that, although common postimmunisation reactions are more frequent in recipients of the adjuvanted vaccine, this vaccine is well tolerated, also after re-immunisation in subsequent influenza seasons. Immunogenicity analyses demonstrate a consistently higher immune response with statistically significant increases of postimmunisation geometric mean titres, and of seroconversion and seroprotection rates compared to non-adjuvanted subunit and split influenza vaccines, particularly for the A/H3N2 and the B strains. The higher immunogenicity profile of the MF59-adjuvanted vaccine is maintained also after subsequent immunisations. An even higher adjuvant effect was shown in subjects with low pre-immunisation titre and in those affected by chronic underlying diseases. In conclusion, the addition of MF59 to subunit influenza vaccines enhances significantly the immune response in elderly subjects without causing clinically important changes in the safety profile of the influenza vaccine. PMID:11257408

  15. Construction and Characterization of an Infectious Vaccinia Virus Recombinant That Expresses the Influenza Hemagglutinin Gene and Induces Resistance to Influenza Virus Infection in Hamsters

    NASA Astrophysics Data System (ADS)

    Smith, Geoffrey L.; Murphy, Brian R.; Moss, Bernard

    1983-12-01

    A DNA copy of the influenza virus hemagglutinin gene, derived from influenza virus A/Jap/305/57 (H2N2) was inserted into the genome of vaccinia virus under the control of an early vaccinia virus promoter. Tissue culture cells infected with the purified recombinant virus synthesized influenza hemagglutinin, which was glycosylated and transported to the cell surface where it could be cleaved with trypsin into HA1 and HA2 subunits. Rabbits and hamsters inoculated intradermally with recombinant virus produced circulating antibodies that inhibited hemagglutination by influenza virus. Furthermore, vaccinated hamsters achieved levels of antibody similar to those obtained upon primary infection with influenza virus and were protected against respiratory infection with the A/Jap/305/57 influenza virus.

  16. Saikosaponin A inhibits influenza A virus replication and lung immunopathology.

    PubMed

    Chen, Jianxin; Duan, Mubing; Zhao, Yaqin; Ling, Fangfang; Xiao, Kun; Li, Qian; Li, Bin; Lu, Chunni; Qi, Wenbao; Zeng, Zhenling; Liao, Ming; Liu, Yahong; Chen, Weisan

    2015-12-15

    Fatal influenza outcomes result from a combination of rapid virus replication and collateral lung tissue damage caused by exaggerated pro-inflammatory host immune cell responses. There are few therapeutic agents that target both biological processes for the attenuation of influenza-induced lung pathology. We show that Saikosaponin A, a bioactive triterpene saponin with previouslyestablished anti-inflammatory effects, demonstrates both in vitro and in vivo anti-viral activity against influenza A virus infections. Saikosaponin A attenuated the replication of three different influenza A virus strains, including a highly pathogenic H5N1 strain, in human alveolar epithelial A549 cells. This anti-viral activity occurred through both downregulation of NF-κB signaling and caspase 3-dependent virus ribonucleoprotein nuclear export as demonstrated by NF-κB subunit p65 and influenza virus nucleoprotein nuclear translocation studies in influenza virus infected A549 cells. Critically, Saikosaponin A also attenuated viral replication, aberrant pro-inflammatory cytokine production and lung histopathology in the widely established H1N1 PR8 model of influenza A virus lethality in C57BL/6 mice. Flow cytometry studies of mouse bronchoalveolar lavage cells revealed that SSa exerted immunomodulatory effects through a selective attenuation of lung neutrophil and monocyte recruitment during the early peak of the innate immune response to PR8 infection. Altogether, our results indicate that Saikosaponin A possesses novel therapeutic potential for the treatment of pathological influenza virus infections. PMID:26637810

  17. Saikosaponin A inhibits influenza A virus replication and lung immunopathology

    PubMed Central

    Zhao, Yaqin; Ling, Fangfang; Xiao, Kun; Li, Qian; Li, Bin; Lu, Chunni; Qi, Wenbao; Zeng, Zhenling; Liao, Ming; Liu, Yahong; Chen, Weisan

    2015-01-01

    Fatal influenza outcomes result from a combination of rapid virus replication and collateral lung tissue damage caused by exaggerated pro-inflammatory host immune cell responses. There are few therapeutic agents that target both biological processes for the attenuation of influenza-induced lung pathology. We show that Saikosaponin A, a bioactive triterpene saponin with previouslyestablished anti-inflammatory effects, demonstrates both in vitro and in vivo anti-viral activity against influenza A virus infections. Saikosaponin A attenuated the replication of three different influenza A virus strains, including a highly pathogenic H5N1 strain, in human alveolar epithelial A549 cells. This anti-viral activity occurred through both downregulation of NF-κB signaling and caspase 3-dependent virus ribonucleoprotein nuclear export as demonstrated by NF-κB subunit p65 and influenza virus nucleoprotein nuclear translocation studies in influenza virus infected A549 cells. Critically, Saikosaponin A also attenuated viral replication, aberrant pro-inflammatory cytokine production and lung histopathology in the widely established H1N1 PR8 model of influenza A virus lethality in C57BL/6 mice. Flow cytometry studies of mouse bronchoalveolar lavage cells revealed that SSa exerted immunomodulatory effects through a selective attenuation of lung neutrophil and monocyte recruitment during the early peak of the innate immune response to PR8 infection. Altogether, our results indicate that Saikosaponin A possesses novel therapeutic potential for the treatment of pathological influenza virus infections. PMID:26637810

  18. A recombinant influenza virus vaccine expressing the F protein of respiratory syncytial virus

    PubMed Central

    Fonseca, Wendy; Ozawa, Makoto; Hatta, Masato; Orozco, Esther; Martínez, Máximo B; Kawaoka, Yoshihiro

    2014-01-01

    Infections with influenza and respiratory syncytial virus (RSV) rank high among the most common human respiratory diseases worldwide. Previously, we developed a replication-incompetent influenza virus by replacing the coding sequence of the PB2 gene, which encodes one of the viral RNA polymerase subunits, with that of a reporter gene. Here, we generated a PB2-knockout recombinant influenza virus expressing the F protein of RSV (PB2-RSVF virus) and tested its potential as a bivalent vaccine. In mice intranasally immunized with the PB2-RSVF virus, we detected high levels of antibodies against influenza virus, but not RSV. PB2-RSVF virus-immunized mice were protected from a lethal challenge with influenza virus but experienced severe body weight loss when challenged with RSV, indicating that PB2-RSVF vaccination enhanced RSV-associated disease. These results highlight one of the difficulties of developing an effective bivalent vaccine against influenza virus and RSV infections. PMID:24292020

  19. Functional Genomics Reveals Linkers Critical for Influenza Virus Polymerase

    PubMed Central

    Wang, Lulan; Wu, Aiping; Wang, Yao E.; Quanquin, Natalie; Li, Chunfeng; Wang, Jingfeng; Chen, Hsiang-Wen; Liu, Suyang; Liu, Ping; Zhang, Hong; Qin, F. Xiao-Feng

    2015-01-01

    ABSTRACT Influenza virus mRNA synthesis by the RNA-dependent RNA polymerase involves binding and cleavage of capped cellular mRNA by the PB2 and PA subunits, respectively, and extension of viral mRNA by PB1. However, the mechanism for such a dynamic process is unclear. Using high-throughput mutagenesis and sequencing analysis, we have not only generated a comprehensive functional map for the microdomains of individual subunits but also have revealed the PA linker to be critical for polymerase activity. This PA linker binds to PB1 and also forms ionic interactions with the PA C-terminal channel. Nearly all mutants with five-amino-acid insertions in the linker were nonviable. Our model further suggests that the PA linker plays an important role in the conformational changes that occur between stages that favor capped mRNA binding and cleavage and those associated with viral mRNA synthesis. IMPORTANCE The RNA-dependent RNA polymerase of influenza virus consists of the PB1, PB2, and PA subunits. By combining genome-wide mutagenesis analysis with the recently discovered crystal structure of the influenza polymerase heterotrimer, we generated a comprehensive functional map of the entire influenza polymerase complex. We identified the microdomains of individual subunits, including the catalytic domains, the interaction interfaces between subunits, and nine linkers interconnecting different domains. Interestingly, we found that mutants with five-amino-acid insertions in individual linkers were nonviable, suggesting the critical roles these linkers play in coordinating spatial relationships between the subunits. We further identified an extended PA linker that binds to PB1 and also forms ionic interactions with the PA C-terminal channel. PMID:26719244

  20. Avian Influenza (Bird Flu)

    MedlinePlus

    ... this page: About CDC.gov . Avian Influenza H5 Viruses in the United States Updates and Publications Information ... Humans Examples of Human Infections with Avian Influenza Viruses Outbreaks Health Care and Laboratorian Guidance HPAI A ...

  1. Haemophilus influenza organism (image)

    MedlinePlus

    ... prior to the widespread use of the H. influenza vaccine). The large red-colored objects are cells in the spinal fluid. A vaccine to prevent infection by Haemophilus influenza (type B) is available as one of the ...

  2. Treating Influenza (Flu)

    MedlinePlus

    ... can be used to treat influenza illness. Antiviral drugs fight influenza viruses in your body. They are different from ... chills and fatigue. Your doctor may prescribe antiviral drugs to treat your flu illness. Should Istill get aflu vaccine? Yes. Antiviral ...

  3. [Influenza virus].

    PubMed

    Juozapaitis, Mindaugas; Antoniukas, Linas

    2007-01-01

    Every year, especially during the cold season, many people catch an acute respiratory disease, namely flu. It is easy to catch this disease; therefore, it spreads very rapidly and often becomes an epidemic or a global pandemic. Airway inflammation and other body ailments, which form in a very short period, torment the patient several weeks. After that, the symptoms of the disease usually disappear as quickly as they emerged. The great epidemics of flu have rather unique characteristics; therefore, it is possible to identify descriptions of such epidemics in historic sources. Already in the 4th century bc, Hippocrates himself wrote about one of them. It is known now that flu epidemics emerge rather frequently, but there are no regular intervals between those events. The epidemics can differ in their consequences, but usually they cause an increased mortality of elderly people. The great flu epidemics of the last century took millions of human lives. In 1918-19, during "The Spanish" pandemic of flu, there were around 40-50 millions of deaths all over the world; "Pandemic of Asia" in 1957 took up to one million lives, etc. Influenza virus can cause various disorders of the respiratory system: from mild inflammations of upper airways to acute pneumonia that finally results in the patient's death. Scientist Richard E. Shope, who investigated swine flu in 1920, had a suspicion that the cause of this disease might be a virus. Already in 1933, scientists from the National Institute for Medical Research in London - Wilson Smith, Sir Christopher Andrewes, and Sir Patrick Laidlaw - for the first time isolated the virus, which caused human flu. Then scientific community started the exhaustive research of influenza virus, and the great interest in this virus and its unique features is still active even today. PMID:18182834

  4. Avian influenza virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Avian influenza virus (AIV) is type A influenza, which is adapted to an avian host. Although avian influenza has been isolated from numerous avian species, the primary natural hosts for the virus are dabbling ducks, shorebirds, and gulls. The virus can be found world-wide in these species and in o...

  5. About Haemophilus influenzae Disease

    MedlinePlus

    ... one that most people are familiar with is Haemophilus influenzae type b, or Hib. There’s a vaccine that can prevent disease caused by Hib, but not the other types of Haemophilus influenzae . Types of Infection Haemophilus influenzae Can Cause Infections ...

  6. Continuing challenges in influenza

    PubMed Central

    Webster, Robert G.; Govorkova, Elena A.

    2014-01-01

    Influenza is an acute respiratory disease in mammals and domestic poultry that emerges from zoonotic reservoirs in aquatic birds and bats. Although influenza viruses are among the most intensively studied pathogens, existing control options require further improvement. Influenza vaccines must be regularly updated because of continuous antigenic drift and sporadic antigenic shifts in the viral surface glycoproteins. Currently, influenza therapeutics are limited to neuraminidase inhibitors; novel drugs and vaccine approaches are therefore urgently needed. Advances in vaccinology and structural analysis have revealed common antigenic epitopes on hemagglutinins across all influenza viruses and suggest that a universal influenza vaccine is possible. In addition, various immunomodulatory agents and signaling pathway inhibitors are undergoing preclinical development. Continuing challenges in influenza include the emergence of pandemic H1N1 influenza in 2009, human infections with avian H7N9 influenza in 2013, and sporadic human cases of highly pathogenic avian H5N1 influenza. Here, we review the challenges facing influenza scientists and veterinary and human public health officials; we also discuss the exciting possibility of achieving the ultimate goal of controlling influenza’s ability to change its antigenicity. PMID:24891213

  7. [Influenza in heterothermic animals].

    PubMed

    Mancini, Dalva Assunção Portari; Mendonça, Rita Maria Zucatelli; Cianciarullo, Aurora Marques; Kobashi, Leonardo Setsuo; Trindade, Hermínio Gomes; Fernandes, Wilson; Pinto, José Ricardo

    2004-01-01

    The objective was to study Orthomyxovirus in heterothermic animals. Blood samples from snakes (genus Bothrops and Crotalus) and from toads and frogs (genus Bufo and Rana) were collected to evaluate the red cell receptors and antibodies specific to influenza virus by the hemagglutination and hemagglutination inhibition tests, respectively. Both snakes and toads kept in captivity presented receptors in their red cells and antibodies specific to either influenza virus type A (human and equine origin) or influenza type B. The same was observed with recently captured snakes. Concerning the influenza hemagglutination inhibition antibodies protective levels were observed in the reptiles' serum, against influenza type A and type B. Unlike the toads, 83.3% of the frogs presented mean levels of Ab 40HIU for some influenza strains. It was concluded that heterothermic animals could offer host conditions to the influenza virus and also susceptibility to the infection. PMID:15330057

  8. Developing vaccines against pandemic influenza.

    PubMed Central

    Wood, J M

    2001-01-01

    Pandemic influenza presents special problems for vaccine development. There must be a balance between rapid availability of vaccine and the safeguards to ensure safety, quality and efficacy of vaccine. Vaccine was developed for the pandemics of 1957, 1968, 1977 and for the pandemic alert of 1976. This experience is compared with that gained in developing vaccines for a possible H5N1 pandemic in 1997-1998. Our ability to mass produce influenza vaccines against a pandemic threat was well illustrated by the production of over 150 million doses of 'swine flu' vaccine in the USA within a 3 month period in 1976. However, there is cause for concern that the lead time to begin vaccine production is likely to be about 7-8 months. Attempts to reduce this time should receive urgent attention. Immunogenicity of vaccines in pandemic situations is compared over the period 1968-1998. A consistent feature of the vaccine trials is the demonstration that one conventional 15 microg haemagglutinin dose of vaccine is not sufficiently immunogenic in naive individuals. Much larger doses or two lower doses are needed to induce satisfactory immunity. There is some evidence that whole-virus vaccines are more immunogenic than split or subunit vaccines, but this needs substantiating by further studies. H5 vaccines appeared to be particularly poor immunogens and there is evidence that an adjuvant may be needed. Prospects for improving the development of pandemic vaccines are discussed. PMID:11779397

  9. Chitosan nanoparticle encapsulated hemagglutinin-split influenza virus mucosal vaccine.

    PubMed

    Sawaengsak, Chompoonuch; Mori, Yasuko; Yamanishi, Koichi; Mitrevej, Ampol; Sinchaipanid, Nuttanan

    2014-04-01

    Subunit/split influenza vaccines are less reactogenic compared with the whole virus vaccines. However, their immunogenicity is relatively low and thus required proper adjuvant and/or delivery vehicle for immunogenicity enhancement. Influenza vaccines administered intramuscularly induce minimum, if any, mucosal immunity at the respiratory mucosa which is the prime site of the infection. In this study, chitosan (CS) nanoparticles were prepared by ionic cross-linking of the CS with sodium tripolyphosphate (TPP) at the CS/TPP ratio of 1:0.6 using 2 h mixing time. The CS/TPP nanoparticles were used as delivery vehicle of an intranasal influenza vaccine made of hemagglutinin (HA)-split influenza virus product. Innocuousness, immunogenicity, and protective efficacy of the CS/TPP-HA vaccine were tested in influenza mouse model in comparison with the antigen alone vaccine. The CS/TPP-HA nanoparticles had required characteristics including nano-sizes, positive charges, and high antigen encapsulation efficiency. Mice that received two doses of the CS/TPP-HA vaccine intranasally showed no adverse symptoms indicating the vaccine innocuousness. The animals developed higher systemic and mucosal antibody responses than vaccine made of the HA-split influenza virus alone. The CS/TPP-HA vaccine could induce also a cell-mediated immune response shown as high numbers of IFN-γ-secreting cells in spleens while the HA vaccine alone could not. Besides, the CS nanoparticle encapsulated HA-split vaccine reduced markedly the influenza morbidity and also conferred 100% protective rate to the vaccinated mice against lethal influenza virus challenge. Overall results indicated that the CS nanoparticles invented in this study is an effective and safe delivery vehicle/adjuvant for the influenza vaccine. PMID:24343789

  10. Analysis of egg-based model wall paintings by use of an innovative combined dot-ELISA and UPLC-based approach.

    PubMed

    Potenza, Mariangela; Sabatino, Giuseppina; Giambi, Francesca; Rosi, Luca; Papini, Anna Maria; Dei, Luigi

    2013-01-01

    The chemical analysis of egg-based wall paintings-the mezzo fresco technique-is an interesting topic in the characterisation of organic binders. A revised procedure for a dot-enzyme-linked immunosorbent assay (dot-ELISA) able to detect protein components of egg-based wall paintings is reported. In the new dot-ELISA procedure we succeeded in maximizing the staining colour by adjusting the temperature during the staining reaction. Quantification of the colour intensity by visible reflectance spectroscopy resulted in a straight line plot of protein concentration against reflectance in the wavelength range 380-780 nm. The modified dot-ELISA procedure is proposed as a semi-quantitative analytical method for characterisation of protein binders in egg-based paintings. To evaluate its performance, the method was first applied to standard samples (ovalbumin, whole egg, egg white), then to model specimens, and finally to real samples (Giotto's wall paintings). Moreover, amino acid analysis performed by innovative ultra-performance liquid chromatography was applied both to standards and to model samples and the results were compared with those from the dot-ELISA tests. In particular, after protein hydrolysis (24 h, 114 °C, 6 mol L(-1) HCl) of the samples, amino acid derivatization by use of 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate enabled reproducible analysis of amino acids. This UPLC amino acid analysis was rapid and reproducible and was applied for the first time to egg-based paintings. Because the painting technique involved the use of egg-based tempera on fresh lime-based mortar, the study enabled investigation of the effect of the alkaline environment on egg-protein detection by both methods. PMID:22614707

  11. Adaptation of high-growth influenza H5N1 vaccine virus in Vero cells: implications for pandemic preparedness.

    PubMed

    Tseng, Yu-Fen; Hu, Alan Yung-Chih; Huang, Mei-Liang; Yeh, Wei-Zhou; Weng, Tsai-Chuan; Chen, Yu-Shuan; Chong, Pele; Lee, Min-Shi

    2011-01-01

    Current egg-based influenza vaccine production technology can't promptly meet the global demand during an influenza pandemic as shown in the 2009 H1N1 pandemic. Moreover, its manufacturing capacity would be vulnerable during pandemics caused by highly pathogenic avian influenza viruses. Therefore, vaccine production using mammalian cell technology is becoming attractive. Current influenza H5N1 vaccine strain (NIBRG-14), a reassortant virus between A/Vietnam/1194/2004 (H5N1) virus and egg-adapted high-growth A/PR/8/1934 virus, could grow efficiently in eggs and MDCK cells but not Vero cells which is the most popular cell line for manufacturing human vaccines. After serial passages and plaque purifications of the NIBRG-14 vaccine virus in Vero cells, one high-growth virus strain (Vero-15) was generated and can grow over 10(8) TCID(50)/ml. In conclusion, one high-growth H5N1 vaccine virus was generated in Vero cells, which can be used to manufacture influenza H5N1 vaccines and prepare reassortant vaccine viruses for other influenza A subtypes. PMID:22022351

  12. Swine Influenza/Variant Influenza Viruses

    MedlinePlus

    ... Humans Key Facts about Human Infections with Variant Viruses Interim Guidance for Clinicians on Human Infections Background, Risk Assessment & Reporting Reported Infections with Variant Influenza Viruses in the United States since 2005 Prevention Treatment ...

  13. Influenza-Sediment Interactions

    NASA Astrophysics Data System (ADS)

    Trusiak, A.; Block, K. A.; Katz, A.; Gottlieb, P.; Alimova, A.; Galarza, J.; Wei, H.; Steiner, J. C.

    2013-12-01

    A typical water fowl can secrete 1012 influenza virions per day. Therefore it is not unexpected that influenza virions interact with sediments in the water column. The influence of sediments on avian influenza virions is not known. With the threat of avian influenza emerging into the human population, it is crucial to understand virus survivability and residence time in a body of water. Influenza and clay sediments are colloidal particles and thus aggregate as explained by DLVO (Derjaguin & Landau, Verwey & Overbeek) theory. Of great importance is an understanding of the types of particulate or macromolecular components that bind the virus particles, and whether the virus remains biologically active. We present results of hetero-aggregation and transmission electron microscopy experiments performed with influenza A/PR8/38. Influenza particles are suspended with sediment and minimal nutrients for several days, after which the components are evaluated to determine influenza concentration and survivability. Transmission electron microscopy results are reported on the influenza-sediment aggregates to elucidate structure and morphology of the components.

  14. Hsp90 inhibitors reduce influenza virus replication in cell culture

    SciTech Connect

    Chase, Geoffrey; Deng, Tao; Fodor, Ervin; Leung, B.W.; Mayer, Daniel; Schwemmle, Martin Brownlee, George

    2008-08-01

    The viral RNA polymerase complex of influenza A virus consists of three subunits PB1, PB2 and PA. Recently, the cellular chaperone Hsp90 was shown to play a role in nuclear import and assembly of the trimeric polymerase complex by binding to PB1 and PB2. Here we show that Hsp90 inhibitors, geldanamycin or its derivative 17-AAG, delay the growth of influenza virus in cell culture resulting in a 1-2 log reduction in viral titre early in infection. We suggest that this is caused by the reduced half-life of PB1 and PB2 and inhibition of nuclear import of PB1 and PA which lead to reduction in viral RNP assembly. Hsp90 inhibitors may represent a new class of antiviral compounds against influenza viruses.

  15. Egg-independent vaccine strategies for highly pathogenic H5N1 influenza viruses.

    PubMed

    Pandey, Aseem; Singh, Neetu; Sambhara, Suryaprakash; Mittal, Suresh K

    2010-02-01

    The emergence of a highly pathogenic H5N1 influenza virus in Hong Kong in 1997 and the subsequent appearance of other H5N1 strains and their spread to several countries in southeast Asia, Africa, the Middle East and Europe has evoked fear of a global influenza pandemic. Vaccines offer the best hope to combat the threat of an influenza pandemic. However, the global demand for a pandemic vaccine cannot be fulfilled by the current egg-based vaccine manufacturing strategies, thus creating a need to explore alternative technologies for vaccine production and delivery. Several egg-independent vaccine approaches such as cell culture-derived whole virus or subvirion vaccines, recombinant protein-based vaccines, virus-like particle (VLP) vaccines, DNA vaccines and viral vector-based vaccines are currently being investigated and appear promising both in preclinical and clinical studies. The present review will highlight the various egg-independent alternative vaccine approaches for pandemic influenza. PMID:19875936

  16. Update: Influenza Activity - United States.

    PubMed

    Smith, Sophie; Blanton, Lenee; Kniss, Krista; Mustaquim, Desiree; Steffens, Craig; Reed, Carrie; Bramley, Anna; Flannery, Brendan; Fry, Alicia M; Grohskopf, Lisa A; Bresee, Joseph; Wallis, Teresa; Garten, Rebecca; Xu, Xiyan; Elal, Anwar Isa Abd; Gubareva, Larisa; Barnes, John; Wentworth, David E; Burns, Erin; Katz, Jacqueline; Jernigan, Daniel; Brammer, Lynnette

    2015-12-11

    CDC collects, compiles, and analyzes data on influenza activity year-round in the United States. The influenza season generally begins in the fall and continues through the winter and spring months; however, the timing and severity of circulating influenza viruses can vary by geographic location and season. Influenza activity in the United States remained low through October and November in 2015. Influenza A viruses have been most frequently identified, with influenza A (H3) viruses predominating. This report summarizes U.S. influenza activity for the period October 4-November 28, 2015. PMID:26656182

  17. INFLUENZA VIRUS IN POULTRY

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Avian influenza virus (AIV) is normally found in wild birds, particularly in ducks and shorebirds, where it does not cause any perceptible clinical disease. However, poultry, including chickens and turkeys, are not normal hosts for avian influenza, but if the virus is introduced it can result in mi...

  18. Influenza A virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Influenza A viruses are important veterinary and human health pathogens around the world. Avian influenza (AI) virus in poultry is unusual in that it can cause a range of disease symptoms from a subclinical infection to being highly virulent with 100% mortality. The difference between low pathogen...

  19. Seasonal Influenza: An Overview

    ERIC Educational Resources Information Center

    Li, Christina; Freedman, Marian

    2009-01-01

    Seasonal influenza is a major cause of morbidity and mortality in the United States. It also has major social and economic consequences in the form of high rates of absenteeism from school and work as well as significant treatment and hospitalization costs. In fact, annual influenza epidemics and the resulting deaths and lost days of productivity…

  20. Influenza vaccination during pregnancy.

    PubMed

    2016-02-01

    In a randomised, double-blind trial in pregnant women, a seasonal inactivated influenza vaccine without a lipid adjuvant and covering strain A/H1N1v was partially effective: the incidence of influenza in the mothers and their infants was about 1.8% with the vaccine versus 3.6% with placebo. No noteworthy adverse reactions were reported. PMID:27042735

  1. Haemophilus Influenzae Type b

    MedlinePlus

    ... Issues Listen Español Text Size Email Print Share Haemophilus Influenzae type b Page Content Article Body If you’re like many parents, you may have been unfamiliar with Haemophilus influenzae type b (Hib) infections until your pediatrician recommended a vaccine ...

  2. Swine Influenza Update

    Technology Transfer Automated Retrieval System (TEKTRAN)

    On April 24, 2009, the Centers for Disease Control (CDC) confirmed an influenza epidemic was occurring in people and the genetic lineage was most closely related to influenza viruses known to be circulating in swine. The outbreak epicenter appeared to be in central Mexico and the virus spread to th...

  3. Influenza. Past, present, and future.

    PubMed

    Regan, Sean F; Fowler, Christianne

    2002-11-01

    Influenza is a viral infection of the respiratory tract spread by airborne transmission. Vaccination remains the best strategy for influenza prevention, and is especially recommended for high-risk groups, such as residents of nursing or residential homes, as well as those with diabetes, chronic renal failure, or chronic respiratory conditions. The clinician must realize the importance of active surveillance in addition to symptomatology interpretation and diagnostic testing to reliably and efficiently diagnose influenza. Active surveillance allows the clinician to monitor regional patterns of influenza movement to know when influenza is present in any given area. Surveillance data allows the practitioner to effectively time vaccination programs and implement prophylaxis protocols as indicated. An influenza management protocol ensuring the prompt recognition and management of influenza outbreaks should be devised and implemented for high-risk facilities. Managing clients with influenza requires prompt diagnosis and initiation of therapy, including use of antivirals available for the prevention or treatment of influenza. Because of the severity of morbidity and mortality caused by the influenza virus among older adults in particular, it is imperative that gerontological nurses have expert knowledge related to influenza. The clinician who participates in active influenza surveillance, promotes vaccination programs, implements influenza management protocols, and stays abreast of recent breakthroughs in the arena of influenza research--such as the development of neuraminidase inhibitors--will be able to contribute to diminishing the morbidity and mortality impact associated with influenza. PMID:12465200

  4. Antiviral activity of crude extracts of Eugenia jambolana Lam. against highly pathogenic avian influenza (H5N1) virus.

    PubMed

    Sood, Richa; Swarup, D; Bhatia, S; Kulkarni, D D; Dey, S; Saini, M; Dubey, S C

    2012-03-01

    Crude extracts of leaves and bark of E. jambolana were tested for antiviral activity against highly pathogenic avian influenza virus (H5N1) by CPE reduction assay in three different layouts to elucidate virucidal, post-exposure and preexposure antiviral activity of the extracts. The cold and hot aqueous extracts of bark and hot aqueous extract of leaves of E. jambolana showed significant virucidal activity (100% inhibition) which was further confirmed in virus yield reduction assay (-98 to 99% reduction) and by egg based in ovo assay. The selective index (CC50/EC50) of hot aqueous extract (248) and cold aqueous extract (43.5) of bark of E. jambolana showed their antiviral potential against H5N1 virus. The significant virucidal activity of leaves and bark of E. jambolana merits further investigation as it may provide alternative antiviral agent for managing avian influenza infections in poultry farms and potential avian-human transmission. PMID:22439432

  5. [Influenza infection and pregnancy].

    PubMed

    Anselem, Olivia; Floret, Daniel; Tsatsaris, Vassilis; Goffinet, François; Launay, Odile

    2013-11-01

    Pregnant woman have an increased risk of respiratory complications and hospitalization related to influenza. The flu, like any systemic infection, may also be responsible for uterine contractions constituting a threat of miscarriage or premature labor according to gestational age at which it occurs. There is no specific recommendation regarding the management of influenza-like illness in pregnant women, but a nasopharyngeal sample can be performed in the presence of respiratory or general symptoms occurring during an epidemic to search influenza and establish if a specific treatment with oseltamivir (Tamiflu(®)). Surveillance in hospital or intensive care unit may be necessary. Vaccination against influenza provides a satisfactory immunity in pregnant women and reduces the risk of respiratory complications. Transplacental passage of maternal antibody protects newborns who are more likely to have severe influenza infection and because the vaccine cannot be administered before the age of 6 months. The available data show good tolerance influenza vaccination performed during pregnancy. Since 2012, vaccination against seasonal influenza is recommended for pregnant women, whatever the stage of pregnancy at the time of the vaccination campaign. PMID:23683385

  6. Human Influenza Virus Infections.

    PubMed

    Peteranderl, Christin; Herold, Susanne; Schmoldt, Carole

    2016-08-01

    Seasonal and pandemic influenza are the two faces of respiratory infections caused by influenza viruses in humans. As seasonal influenza occurs on an annual basis, the circulating virus strains are closely monitored and a yearly updated vaccination is provided, especially to identified risk populations. Nonetheless, influenza virus infection may result in pneumonia and acute respiratory failure, frequently complicated by bacterial coinfection. Pandemics are, in contrary, unexpected rare events related to the emergence of a reassorted human-pathogenic influenza A virus (IAV) strains that often causes increased morbidity and spreads extremely rapidly in the immunologically naive human population, with huge clinical and economic impact. Accordingly, particular efforts are made to advance our knowledge on the disease biology and pathology and recent studies have brought new insights into IAV adaptation mechanisms to the human host, as well as into the key players in disease pathogenesis on the host side. Current antiviral strategies are only efficient at the early stages of the disease and are challenged by the genomic instability of the virus, highlighting the need for novel antiviral therapies targeting the pulmonary host response to improve viral clearance, reduce the risk of bacterial coinfection, and prevent or attenuate acute lung injury. This review article summarizes our current knowledge on the molecular basis of influenza infection and disease progression, the key players in pathogenesis driving severe disease and progression to lung failure, as well as available and envisioned prevention and treatment strategies against influenza virus infection. PMID:27486731

  7. Epidemiology and control of influenza.

    PubMed

    Rao, B L

    2003-01-01

    Influenza causes frequent epidemics and periodic pandemics, and is a major public health problem. Pandemics occurred in 1918 (swine influenza), 1957 (Asian influenza), 1968 (Hong Kong influenza) and 1977 (Russian influenza) due to major antigenic variation of the type A influenza virus. Frequent epidemics occur after pandemics as a result of minor antigenic variation of the pandemic virus strains. Minor antigenic variant strains of type A (H1N1), A (H3N2) and type B influenza viruses are currently circulating globally, causing frequent epidemics. The World Health Organization (WHO) has established a network of National Influenza Centres all over the world to study the epidemiology and ecology of influenza, and collaborating centres for updating the influenza vaccines and other research activities. As a part of this programme, it has set up the WHO Flunet for disseminating updates on the global influenza situation, current vaccines and antiviral drugs. Some National Influenza Centres in India have investigated and reported pandemics and epidemics caused by global influenza virus strains during the past 50 years. There is a need to expand influenza surveillance in our country, as only a few centres are conducting these studies. PMID:12929857

  8. Characterization of Influenza Vaccine Hemagglutinin Complexes by Cryo-Electron Microscopy and Image Analyses Reveals Structural Polymorphisms.

    PubMed

    McCraw, Dustin M; Gallagher, John R; Harris, Audray K

    2016-06-01

    Influenza virus afflicts millions of people worldwide on an annual basis. There is an ever-present risk that animal viruses will cross the species barrier to cause epidemics and pandemics resulting in great morbidity and mortality. Zoonosis outbreaks, such as the H7N9 outbreak, underscore the need to better understand the molecular organization of viral immunogens, such as recombinant influenza virus hemagglutinin (HA) proteins, used in influenza virus subunit vaccines in order to optimize vaccine efficacy. Here, using cryo-electron microscopy and image analysis, we show that recombinant H7 HA in vaccines formed macromolecular complexes consisting of variable numbers of HA subunits (range, 6 to 8). In addition, HA complexes were distributed across at least four distinct structural classes (polymorphisms). Three-dimensional (3D) reconstruction and molecular modeling indicated that HA was in the prefusion state and suggested that the oligomerization and the structural polymorphisms observed were due to hydrophobic interactions involving the transmembrane regions. These experiments suggest that characterization of the molecular structures of influenza virus HA complexes used in subunit vaccines will lead to better understanding of the differences in vaccine efficacy and to the optimization of subunit vaccines to prevent influenza virus infection. PMID:27074939

  9. Characterization of Influenza Vaccine Hemagglutinin Complexes by Cryo-Electron Microscopy and Image Analyses Reveals Structural Polymorphisms

    PubMed Central

    McCraw, Dustin M.; Gallagher, John R.

    2016-01-01

    Influenza virus afflicts millions of people worldwide on an annual basis. There is an ever-present risk that animal viruses will cross the species barrier to cause epidemics and pandemics resulting in great morbidity and mortality. Zoonosis outbreaks, such as the H7N9 outbreak, underscore the need to better understand the molecular organization of viral immunogens, such as recombinant influenza virus hemagglutinin (HA) proteins, used in influenza virus subunit vaccines in order to optimize vaccine efficacy. Here, using cryo-electron microscopy and image analysis, we show that recombinant H7 HA in vaccines formed macromolecular complexes consisting of variable numbers of HA subunits (range, 6 to 8). In addition, HA complexes were distributed across at least four distinct structural classes (polymorphisms). Three-dimensional (3D) reconstruction and molecular modeling indicated that HA was in the prefusion state and suggested that the oligomerization and the structural polymorphisms observed were due to hydrophobic interactions involving the transmembrane regions. These experiments suggest that characterization of the molecular structures of influenza virus HA complexes used in subunit vaccines will lead to better understanding of the differences in vaccine efficacy and to the optimization of subunit vaccines to prevent influenza virus infection. PMID:27074939

  10. New treatments for influenza

    PubMed Central

    2012-01-01

    Influenza has a long history of causing morbidity and mortality in the human population through routine seasonal spread and global pandemics. The high mutation rate of the RNA genome of the influenza virus, combined with assortment of its multiple genomic segments, promote antigenic diversity and new subtypes, allowing the virus to evade vaccines and become resistant to antiviral drugs. There is thus a continuing need for new anti-influenza therapy using novel targets and creative strategies. In this review, we summarize prospective future therapeutic regimens based on recent molecular and genomic discoveries. PMID:22973873

  11. Recombinant influenza vaccines.

    PubMed

    Sedova, E S; Shcherbinin, D N; Migunov, A I; Smirnov, Iu A; Logunov, D Iu; Shmarov, M M; Tsybalova, L M; Naroditskiĭ, B S; Kiselev, O I; Gintsburg, A L

    2012-10-01

    This review covers the problems encountered in the construction and production of new recombinant influenza vaccines. New approaches to the development of influenza vaccines are investigated; they include reverse genetics methods, production of virus-like particles, and DNA- and viral vector-based vaccines. Such approaches as the delivery of foreign genes by DNA- and viral vector-based vaccines can preserve the native structure of antigens. Adenoviral vectors are a promising gene-delivery platform for a variety of genetic vaccines. Adenoviruses can efficiently penetrate the human organism through mucosal epithelium, thus providing long-term antigen persistence and induction of the innate immune response. This review provides an overview of the practicability of the production of new recombinant influenza cross-protective vaccines on the basis of adenoviral vectors expressing hemagglutinin genes of different influenza strains. PMID:23346377

  12. Transmission of Flu (Influenza)

    MedlinePlus

    ... Skip Content Marketing Share this: Main Content Area Flu (Influenza) Transmission How Flu Spreads Coughing and Sneezing People with flu can ... not be shared without washing thoroughly first. The Flu Is Contagious You may be able to pass ...

  13. United States of America Department of Health and Human Services support for advancing influenza vaccine manufacturing in the developing world.

    PubMed

    Perdue, Michael L; Bright, Rick A

    2011-07-01

    five years of age. In addition to achievements described in this issue of Vaccine, the programme has been successful from the US perspective because the working relationships established between the US Department of Health and Human Services' (HHS) Assistant Secretary for Preparedness and Response Biomedical Advanced Research and Development Authority (BARDA) and its partners have assisted in advancing influenza vaccine development at many different levels. A few examples of BARDA's support include: establishment of egg-based influenza vaccine production from "scratch", enhancement of live attenuated influenza vaccine (LAIV) production techniques and infrastructure, completion of fill/finish operations for imported bulk vaccine, and training in advanced bio-manufacturing techniques. These HHS-supported programmes have been well-received internationally, and we and our partners hope the successes will stimulate even more interest within the international community in maximizing global production levels for influenza vaccines. PMID:21684430

  14. Pregnant Women and Influenza (Flu)

    MedlinePlus

    ... Medscape Podcasts Public Service Announcements (PSAs) Virus Images Influenza Types Seasonal Avian Swine Variant Pandemic Other Get ... What's this? Submit Button Past Newsletters Pregnant Women & Influenza (Flu) Language: English Español Recommend on Facebook ...

  15. Current developments in avian influenza vaccines, including safety of vaccinated birds as food.

    PubMed

    Swayne, D E; Suarez, D L

    2007-01-01

    Until recently, most vaccines against avian influenza were based on oil-emulsified inactivated low- or high-pathogenicity viruses. Now, recombinant fowl pox and avian paramyxovirus type 1 vaccines with avian influenza H5 gene inserts (+ or - N1 gene insert) are available and licensed. New technologies might overcome existing limitations to make available vaccines that can be grown in tissue culture systems for more rapid production; provide optimized protection, as a result of closer genetic relations to field viruses; allow mass administration by aerosol, in drinking-water or in ovo; and allow easier strategies for identifying infected birds within vaccinated populations (DIVA). The technologies include avian influenza viruses with partial gene deletions, avian influenza-Newcastle disease virus chimeras, vectored vaccines such as adenoviruses and Marek's disease virus, and subunit vaccines. These new methods should be licensed only after their purity, safety, efficacy and potency against avian influenza viruses have been demonstrated, and, for live vectored vaccines, restriction of viral transmission to unvaccinated birds. Use of vaccines in countries affected by highly pathogenic avian influenza will not only protect poultry but will provide additional safety for consumers. Experimental studies have shown that birds vaccinated against avian influenza have no virus in meat and minimal amounts in eggs after HPAI virus challenge, and that replication and shedding from their respiratory and alimentary tracts is greatly reduced. PMID:18411943

  16. Strengthening the influenza vaccine virus selection and development process: Report of the 3rd WHO Informal Consultation for Improving Influenza Vaccine Virus Selection held at WHO headquarters, Geneva, Switzerland, 1-3 April 2014.

    PubMed

    Ampofo, William K; Azziz-Baumgartner, Eduardo; Bashir, Uzma; Cox, Nancy J; Fasce, Rodrigo; Giovanni, Maria; Grohmann, Gary; Huang, Sue; Katz, Jackie; Mironenko, Alla; Mokhtari-Azad, Talat; Sasono, Pretty Multihartina; Rahman, Mahmudur; Sawanpanyalert, Pathom; Siqueira, Marilda; Waddell, Anthony L; Waiboci, Lillian; Wood, John; Zhang, Wenqing; Ziegler, Thedi

    2015-08-26

    investigations but could drive a new surveillance paradigm. However, despite the advances made, significant challenges will need to be addressed before next-generation technologies become routine, particularly in low-resource settings. Emerging approaches and techniques such as synthetic genomics, systems genetics, systems biology and mathematical modelling are capable of generating potentially huge volumes of highly complex and diverse datasets. Harnessing the currently theoretical benefits of such bioinformatics ("big data") concepts for the influenza vaccine virus selection and development process will depend upon further advances in data generation, integration, analysis and dissemination. Over the last decade, growing awareness of influenza as an important global public health issue has been coupled to ever-increasing demands from the global community for more-equitable access to effective and affordable influenza vaccines. The current influenza vaccine landscape continues to be dominated by egg-based inactivated and live attenuated vaccines, with a small number of cell-based and recombinant vaccines. Successfully completing each step in the annual influenza vaccine manufacturing cycle will continue to rely upon timely and regular communication between the WHO GISRS, manufacturers and regulatory authorities. While the pipeline of influenza vaccines appears to be moving towards a variety of niche products in the near term, it is apparent that the ultimate aim remains the development of effective "universal" influenza vaccines that offer longer-lasting immunity against a broad range of influenza A subtypes. PMID:26148877

  17. Improving pandemic influenza risk assessment

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Assessing the pandemic risk posed by specific non-human influenza A viruses remains a complex challenge. As influenza virus genome sequencing becomes cheaper, faster and more readily available, the ability to predict pandemic potential from sequence data could transform pandemic influenza risk asses...

  18. Influenza Vaccines: Challenges and Solutions

    PubMed Central

    Houser, Katherine; Subbarao, Kanta

    2015-01-01

    Vaccination is the best method for the prevention and control of influenza. Vaccination can reduce illness and lessen severity of infection. This review focuses on how currently licensed influenza vaccines are generated in the U.S., why the biology of influenza poses vaccine challenges, and vaccine approaches on the horizon that address these challenges. PMID:25766291

  19. Influenza pandemic planning.

    PubMed

    Cox, Nancy J; Tamblyn, Susan E; Tam, Theresa

    2003-05-01

    Periodically, novel influenza viruses emerge and spread rapidly through susceptible populations, resulting in worldwide epidemics or pandemics. Three pandemics occurred in the 20th century. The first and most devastating of these, the "Spanish Flu" (A/H1N1) pandemic of 1918-1919, is estimated to have resulted in 20-50 million or more deaths worldwide, with unusually high mortality among young adults [C.W. Potter, Chronicle of influenza pandemics, in: K.G. Nicholson, R.G. Webster, A.J. Hay (Eds.), Textbook of Influenza, Blackwell Science, Oxford, 1998, p. 3]. Mortality associated with the 1957 "Asian Flu" (A/H2N2) and the 1968 "Hong Kong Flu" (A/H3N2) pandemics was less severe, with the highest excess mortality in the elderly and persons with chronic diseases [J. Infect. Dis. 178 (1998) 53]. However, considerable morbidity, social disruption and economic loss occurred during both of these pandemics [J. Infect. Dis. 176 (Suppl. 1) (1997) S4]. It is reasonable to assume that future influenza pandemics will occur, given historical evidence and current understanding of the biology, ecology, and epidemiology of influenza. Influenza viruses are impossible to eradicate, as there is a large reservoir of all subtypes of influenza A viruses in wild aquatic birds. In agricultural-based communities with high human population density such as are found in China, conditions exist for the emergence and spread of pandemic viruses. It is also impossible to predict when the next pandemic will occur. Moreover, the severity of illness is also unpredictable, so contingency plans must be put in place now during the inter-pandemic period. These plans must be flexible enough to respond to different levels of disease. PMID:12686098

  20. Domestic influenza vaccine production in Mexico: a state-owned and a multinational company working together for public health.

    PubMed

    Ponce-de-Leon, Samuel; Velazquez-Fernandez, Ruth; Bugarin-González, Jose; García-Bañuelos, Pedro; Lopez-Sotelo, Angelica; Jimenez-Corona, María-Eugenia; Padilla-Catalan, Francisco; Cervantes-Rosales, Rocio

    2011-07-01

    The Mexican Government developed a plan in 2004 for pandemic influenza preparedness that included local production of influenza vaccine. To achieve this, an agreement was concluded between Birmex - a state-owned vaccine manufacturer - and sanofi pasteur, a leading developer of vaccine technology. Under this agreement, sanofi pasteur will establish a facility in Mexico to produce antigen for up to 30 million doses of egg-based seasonal vaccine per year, and Birmex will build a facility to formulate, fill and package the inactivated split-virion influenza vaccine. As at November 2010, the sanofi pasteur facility has been completed and the Birmex plant is under construction. Most of the critical equipment has been purchased and is in the process of validation. In addition to intensive support from sanofi pasteur for the transfer of the technology, the project is supported by the Mexican Ministry of Health, complemented by Birmex's own budget and grants from the WHO developing country influenza technology transfer project. PMID:21684424

  1. Interaction of factor XIII subunits.

    PubMed

    Katona, Eva; Pénzes, Krisztina; Csapó, Andrea; Fazakas, Ferenc; Udvardy, Miklós L; Bagoly, Zsuzsa; Orosz, Zsuzsanna Z; Muszbek, László

    2014-03-13

    Coagulation factor XIII (FXIII) is a heterotetramer consisting of 2 catalytic A subunits (FXIII-A2) and 2 protective/inhibitory B subunits (FXIII-B2). FXIII-B, a mosaic protein consisting of 10 sushi domains, significantly prolongs the lifespan of catalytic subunits in the circulation and prevents their slow progressive activation in plasmatic conditions. In this study, the biochemistry of the interaction between the 2 FXIII subunits was investigated. Using a surface plasmon resonance technique and an enzyme-linked immunosorbent assay-type binding assay, the equilibrium dissociation constant (Kd) for the interaction was established in the range of 10(-10) M. Based on the measured Kd, it was calculated that in plasma approximately 1% of FXIII-A2 should be in free form. This value was confirmed experimentally by measuring FXIII-A2 in plasma samples immunodepleted of FXIII-A2B2. Free plasma FXIII-A2 is functionally active, and when activated by thrombin and Ca(2+), it can cross-link fibrin. In cerebrospinal fluid and tears with much lower FXIII subunit concentrations, >80% of FXIII-A2 existed in free form. A monoclonal anti-FXIII-B antibody that prevented the interaction between the 2 subunits reacted with the recombinant combined first and second sushi domains of FXIII-B, and its epitope was localized to the peptide spanning positions 96 to 103 in the second sushi domain. PMID:24408323

  2. Fragment-Based Identification of Influenza Endonuclease Inhibitors.

    PubMed

    Credille, Cy V; Chen, Yao; Cohen, Seth M

    2016-07-14

    The influenza virus is responsible for millions of cases of severe illness annually. Yearly variance in the effectiveness of vaccination, coupled with emerging drug resistance, necessitates the development of new drugs to treat influenza infections. One attractive target is the RNA-dependent RNA polymerase PA subunit. Herein we report the development of inhibitors of influenza PA endonuclease derived from lead compounds identified from a metal-binding pharmacophore (MBP) library screen. Pyromeconic acid and derivatives thereof were found to be potent inhibitors of endonuclease. Guided by modeling and previously reported structural data, several sublibraries of molecules were elaborated from the MBP hits. Structure-activity relationships were established, and more potent molecules were designed and synthesized using fragment growth and fragment merging strategies. This approach ultimately resulted in the development of a lead compound with an IC50 value of 14 nM, which displayed an EC50 value of 2.1 μM against H1N1 influenza virus in MDCK cells. PMID:27291165

  3. Possible repurposing of seasonal influenza vaccine for prevention of Zika virus infection

    PubMed Central

    Veljkovic, Veljko; Paessler, Slobodan

    2016-01-01

    The in silico analysis shows that the envelope glycoproteins E of Zika viruses (ZIKV) isolated in Asia, Africa and South and Central America encode highly conserved information determining their interacting profile and immunological properties. Previously it was shown that the same information is encoded in the primary structure of the hemagglutinin subunit 1 (HA1) from pdmH1N1 influenza A virus.  This similarity suggests possible repurposing of the seasonal influenza vaccine containing pdmH1N1 component for prevention of the ZIKV infection. PMID:27158449

  4. Possible repurposing of seasonal influenza vaccine for prevention of Zika virus infection.

    PubMed

    Veljkovic, Veljko; Paessler, Slobodan

    2016-01-01

    The in silico analysis shows that the envelope glycoproteins E of Zika viruses (ZIKV) isolated in Asia, Africa and South and Central America encode highly conserved information determining their interacting profile and immunological properties. Previously it was shown that the same information is encoded in the primary structure of the hemagglutinin subunit 1 (HA1) from pdmH1N1 influenza A virus.  This similarity suggests possible repurposing of the seasonal influenza vaccine containing pdmH1N1 component for prevention of the ZIKV infection. PMID:27158449

  5. Influenza Vaccines: Unmet Needs and Recent Developments

    PubMed Central

    Noh, Ji Yun

    2013-01-01

    Influenza is a worldwide public health concern. Since the introduction of trivalent influenza vaccine in 1978, vaccination has been the primary means of prevention and control of influenza. Current influenza vaccines have moderate efficacy, good safety, and acceptable tolerability; however, they have unsatisfactory efficacy in older adults, are dependent on egg supply for production, and are time-consuming to manufacture. This review outlines the unmet medical needs of current influenza vaccines. Recent developments in influenza vaccines are also described. PMID:24475351

  6. Preliminary Proteomic Analysis of A549 Cells Infected with Avian Influenza Virus H7N9 and Influenza A Virus H1N1

    PubMed Central

    Ding, Xiaoman; Lu, Jiahai; Yu, Ruoxi; Wang, Xin; Wang, Ting; Dong, Fangyuan; Peng, Bo; Wu, Weihua; Liu, Hui; Geng, Yijie; Zhang, Renli; Ma, Hanwu; Cheng, Jinquan; Yu, Muhua; Fang, Shisong

    2016-01-01

    A newly emerged H7N9 influenza virus poses high risk to human beings. However, the pathogenic mechanism of the virus remains unclear. The temporal response of primary human alveolar adenocarcinoma epithelial cells (A549) infected with H7N9 influenza virus and H1N1 influenza A virus (H1N1, pdm09) were evaluated using the proteomics approaches (2D-DIGE combined with MALDI-TOF-MS/MS) at 24, 48 and 72 hours post of the infection (hpi). There were 11, 12 and 33 proteins with significant different expressions (P<0.05) at 24, 48 and 72hpi, especially F-actin-capping protein subunit alpha-1 (CAPZA1), Ornithine aminotransferase (OAT), Poly(rC)-binding protein 1 (PCBP1), Eukaryotic translation initiation factor 5A-1 (EIF5A) and Platelet-activating factor acetylhydrolaseⅠb subunit beta (PAFAH1B2) were validated by western-blot analysis. The functional analysis revealed that the differential proteins in A549 cells involved in regulating cytopathic effect. Among them, the down-regulation of CAPZA1, OAT, PCBP1, EIF5A are related to the death of cells infected by H7N9 influenza virus. This is the first time show that the down-regulation of PAFAH1B2 is related to the later clinical symptoms of patients infected by H7N9 influenza virus. These findings may improve our understanding of pathogenic mechanism of H7N9 influenza virus in proteomics. PMID:27223893

  7. Seasonal influenza: an overview.

    PubMed

    Li, Christina; Freedman, Marian

    2009-02-01

    Seasonal influenza is a major cause of morbidity and mortality in the United States. It also has major social and economic consequences in the form of high rates of absenteeism from school and work as well as significant treatment and hospitalization costs. In fact, annual influenza epidemics and the resulting deaths and lost days of productivity are estimated to cost US$10.4 billion in direct medical expenses and US$16.4 billion in lost potential earnings. Given the enormous burden of seasonal influenza and the important role that school-age children play in the cycle of disease, school nurses need to be knowledgeable about all aspects of this condition, including its clinical course and how it is transmitted; the range of options for preventing and treating the disease; and steps that can be taken to improve the rates of immunization against influenza. School nurses also can help by making sure that they themselves are vaccinated in a timely manner. PMID:19197008

  8. [Influenza pandemic: Mexico's response].

    PubMed

    Kuri-Morales, Pablo; Betancourt-Cravioto, Miguel; Velázquez-Monroy, Oscar; Alvarez-Lucas, Carlos; Tapia-Conyer, Roberto

    2006-01-01

    In 1992, a new type of influenza virus appeared in Southeast Asia. This new strain has caused to date, more than 120 cases and over 60 deaths in Cambodia,Vietnam, Indonesia and Thailand. This situation is seen by the experts as the possible genesis of a new influenza pandemic with the corresponding negative effects on the health of the population, international commerce and world economy. In order to face the coming challenge, the World Health Organization (WHO) has asked member countries to develop national preparedness and response plans for an influenza pandemic. Within the framework of the National Committee for Health Security, Mexico has developed a National Preparedness and Response Plan for an Influenza Pandemic with the aim of protecting the health of the population with timely and effective measures. The Plan is based on a risk scale and five lines of action: Coordination, Epidemiological Surveillance, Medical Care, Risk Communication and Strategic Stockpile. It is currently impossible to predict when the next pandemic will start or what will be its impact. Nevertheless, it is fundamental that national and regional health authorities establish measures for protecting the health of the population in case this emergency occurs. PMID:16555537

  9. INFLUENZA AND PNEUMONIA

    PubMed Central

    1916-01-01

    This symposium summarizes the opinions of several widely known health workers on the modes of infection, spread, prevalence and nature, epidemiology, and legislative and executive management of influenza and pneumonia—the two diseases which so greatly increased our morbidity rates during the winter season. PMID:18009431

  10. Avian influenza: recent developments.

    PubMed

    Capua, Ilaria; Alexander, Dennis J

    2004-08-01

    This paper reviews the worldwide situation regarding avian influenza infections in poultry from 1997 to March 2004. The increase in the number of primary introductions and the scientific data available on the molecular basis of pathogenicity have generated concerns particularly for legislative purposes and for international trade. This has led to a new proposed definition of 'avian influenza' to extend all infections caused by H5 and H7 viruses regardless of their virulence as notifiable diseases, although this has encountered some difficulties in being approved. The paper also reviews the major outbreaks caused by viruses of the H5 or H7 subtype and the control measures applied. The zoonotic aspects of avian influenza, which until 1997 were considered to be of limited relevance in human medicine, are also discussed. The human health implications have now gained importance, both for illness and fatalities that have occurred following natural infection with avian viruses, and for the potential of generating a reassortant virus that could give rise to the next human influenza pandemic. PMID:15370036

  11. Avian influenza (fowl plague)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Avian influenza (AI) viruses infect domestic poultry and wild birds. In domestic poultry, AI viruses are typically of low pathogenicity (LP) causing subclinical infections, respiratory disease or drops in egg production. However, a few AI viruses cause severe systemic disease with high mortality; ...

  12. Safety, tolerability and immunogenicity of a mammalian cell-culture-derived influenza vaccine: a sequential Phase I and Phase II clinical trial.

    PubMed

    Groth, N; Montomoli, E; Gentile, C; Manini, I; Bugarini, R; Podda, A

    2009-01-29

    This sequential, observer-blind, randomised, single-centre, combined Phase I and Phase II clinical trial compared the tolerability and immunogenicity of a single intramuscular dose of a novel cell-culture-derived influenza vaccine (CCIV), produced in Madin-Darby canine kidney cells, with a conventional egg-based vaccine. The immunogenicity of both vaccines was assessed by SRH assay, a well-recognized test by EMEA, in compliance with the requirements of the EU Committee for Medicinal Products for Human Use (CHMP). The Phase I part of the trial comprised 40 healthy adults (18-40 years of age); the subsequent Phase II part involved 200 healthy adult (n=80, 18-60 years of age) and elderly (n=120, > or =61 years of age) subjects. Both vaccines showed similar reactogenicity and any solicited local or systemic reactions were mostly mild or moderate. Regarding immunogenicity, both the CCIV and the control vaccine met all of the EU Committee for Medicinal Products for Human Use criteria for influenza vaccines for each strain and in both age groups. In conclusion, the CCIV produced in mammalian cell-culture is as well tolerated and as immunogenic as the control egg-based vaccine in non-elderly and elderly adults. PMID:19027046

  13. Influenza infection in wild raccoons

    USGS Publications Warehouse

    Hall, J.S.; Bentler, K.T.; Landolt, G.; Elmore, S.A.; Minnis, R.B.; Campbell, T.A.; Barras, S.C.; Root, J.J.; Pilon, J.; Pabilonia, K.; Driscoll, C.; Slate, D.; Sullivan, H.; McLean, R.G.

    2008-01-01

    Raccoons (Procyon lotor) are common, widely distributed animals that frequently come into contact with wild waterfowl, agricultural operations, and humans. Serosurveys showed that raccoons are exposed to avian influenza virus. We found antibodies to a variety of influenza virus subtypes (H10N7, H4N6, H4N2, H3, and H1) with wide geographic variation in seroprevalence. Experimental infection studies showed that raccoons become infected with avian and human influenza A viruses, shed and transmit virus to virus-free animals, and seroconvert. Analyses of cellular receptors showed that raccoons have avian and human type receptors with a similar distribution as found in human respiratory tracts. The potential exists for co-infection of multiple subtypes of influenza virus with genetic reassortment and creation of novel strains of influenza virus. Experimental and field data indicate that raccoons may play an important role in influenza disease ecology and pose risks to agriculture and human health.

  14. Interactome Analysis of the Influenza A Virus Transcription/Replication Machinery Identifies Protein Phosphatase 6 as a Cellular Factor Required for Efficient Virus Replication

    PubMed Central

    York, Ashley; Hutchinson, Edward C.

    2014-01-01

    ABSTRACT The negative-sense RNA genome of influenza A virus is transcribed and replicated by the viral RNA-dependent RNA polymerase (RdRP). The viral RdRP is an important host range determinant, indicating that its function is affected by interactions with cellular factors. However, the identities and the roles of most of these factors remain unknown. Here, we employed affinity purification followed by mass spectrometry to identify cellular proteins that interact with the influenza A virus RdRP in infected human cells. We purified RdRPs using a recombinant influenza virus in which the PB2 subunit of the RdRP is fused to a Strep-tag. When this tagged subunit was purified from infected cells, copurifying proteins included the other RdRP subunits (PB1 and PA) and the viral nucleoprotein and neuraminidase, as well as 171 cellular proteins. Label-free quantitative mass spectrometry revealed that the most abundant of these host proteins were chaperones, cytoskeletal proteins, importins, proteins involved in ubiquitination, kinases and phosphatases, and mitochondrial and ribosomal proteins. Among the phosphatases, we identified three subunits of the cellular serine/threonine protein phosphatase 6 (PP6), including the catalytic subunit PPP6C and regulatory subunits PPP6R1 and PPP6R3. PP6 was found to interact directly with the PB1 and PB2 subunits of the viral RdRP, and small interfering RNA (siRNA)-mediated knockdown of the catalytic subunit of PP6 in infected cells resulted in the reduction of viral RNA accumulation and the attenuation of virus growth. These results suggest that PP6 interacts with and positively regulates the activity of the influenza virus RdRP. IMPORTANCE Influenza A viruses are serious clinical and veterinary pathogens, causing substantial health and economic impacts. In addition to annual seasonal epidemics, occasional global pandemics occur when viral strains adapt to humans from other species. To replicate efficiently and cause disease, influenza

  15. The ribosomal subunit assembly line

    PubMed Central

    Dlakić, Mensur

    2005-01-01

    Recent proteomic studies in Saccharomyces cerevisiae have identified nearly 200 proteins, other than the structural ribosomal proteins, that participate in the assembly of ribosomal subunits and their transport from the nucleus. In a separate line of research, proteomic studies of mature plant ribosomes have revealed considerable variability in the protein composition of individual ribosomes. PMID:16207363

  16. Thermostable Subunit Vaccines for Pulmonary Delivery: How Close Are We?

    PubMed

    Foged, Camilla

    2016-01-01

    In the past century, vaccines have contributed to a significant improvement in global public health by preventing a number of infectious diseases. Despite this, the vaccine field is still facing challenges related to incomplete vaccine coverage and persistent difficult vaccine targets, such as influenza, tuberculosis, and Ebola, for which no good universal vaccines exist. At least two pharmaceutical improvements are expected to help filling this gap: i) The development of thermostable vaccine dosage forms, and ii) the full exploitation of the adjuvant technology for subunit vaccines to potentiate strong immune responses. This review highlights the status and recent advances in formulation and pulmonary delivery of thermostable human subunit vaccines. Such vaccines are very appealing from compliance, distribution and immunological point of view: Being non-invasive, inhalable vaccines are self-administrable, can be distributed independently of functioning freezers and refrigerators, and can be designed to induce mucosal and/or cell-mediated immunity, which is attractive for a number of diseases requiring stimulation of local mucosal immunity for protection. However, the design and delivery of thermostable dry powder-based vaccines represents a technological challenge: It calls for careful formulation and dosage form design, combined with cheap and efficient delivery devices, which must be engineered via a thorough understanding of the physiological barrier and the requirements for induction of mucosal immunity. Here, I review state of the art and perspectives in formulation design and processing methods for powder-based subunit vaccines intended for pulmonary administration, and present dry powder inhaler technologies suitable for translating these vaccines into clinical trials. PMID:26831645

  17. Characterization of PA-N terminal domain of Influenza A polymerase reveals sequence specific RNA cleavage.

    PubMed

    Datta, Kausiki; Wolkerstorfer, Andrea; Szolar, Oliver H J; Cusack, Stephen; Klumpp, Klaus

    2013-09-01

    Influenza virus uses a unique cap-snatching mechanism characterized by hijacking and cleavage of host capped pre-mRNAs, resulting in short capped RNAs, which are used as primers for viral mRNA synthesis. The PA subunit of influenza polymerase carries the endonuclease activity that catalyzes the host mRNA cleavage reaction. Here, we show that PA is a sequence selective endonuclease with distinct preference to cleave at the 3' end of a guanine (G) base in RNA. The G specificity is exhibited by the native influenza polymerase complex associated with viral ribonucleoprotein particles and is conferred by an intrinsic G specificity of the isolated PA endonuclease domain PA-Nter. In addition, RNA cleavage site choice by the full polymerase is also guided by cap binding to the PB2 subunit, from which RNA cleavage preferentially occurs at the 12th nt downstream of the cap. However, if a G residue is present in the region of 10-13 nucleotides from the cap, cleavage preferentially occurs at G. This is the first biochemical evidence of influenza polymerase PA showing intrinsic sequence selective endonuclease activity. PMID:23847103

  18. Individual expression of influenza virus PA protein induces degradation of coexpressed proteins.

    PubMed Central

    Sanz-Ezquerro, J J; de la Luna, S; Ortín, J; Nieto, A

    1995-01-01

    In the process of in vivo reconstitution of influenza virus transcriptase-replicase complex, an inhibitory effect was observed when the level of PA protein expression was increased. This inhibition was paralleled by a decrease in the accumulation of the other influenza virus core proteins. The sole expression of PA protein was sufficient to reduce the accumulation level of the proteins encoded by the coexpressed genes. The PA effect was observed upon influenza virus and non-influenza virus proteins and independently of the expression system chosen and the origin of cell line used. The expression of PA protein did not induce variations in the translation of the target proteins but did induce variations on their half-lives, which were clearly reduced. A functional PA subunit seems to be necessary to induce this negative effect, because an inactive point mutant was unable to decrease the steady-state levels or the half-lives of the reporter proteins. The PA effect was observed as early as 5 h after its expression, and continuous synthesis of proteins was not required for performance of its biological activity. The results presented represent the first biological activity of individually expressed PA polymerase subunit. PMID:7884889

  19. H1N1 influenza (Swine flu)

    MedlinePlus

    Swine flu; H1N1 type A influenza ... of the H1N1 virus were found in pigs (swine). Over time, the virus changed (mutated) and infected ... 25654610 . Treanor JJ. Influenza (including avian influenza and swine influenza). In: Bennett JE, Dolin R, Blaser MJ, ...

  20. Pathobiology of avian influenza viruses

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Avian influenza virus causes serious disease in a wide variety of birds and mammals. Its natural hosts are wild aquatic birds, in which most infections are unapparent. Avian Influenza (AI) viruses are classified into 16 hemagglutinin (H1-16) and nine neuraminidase (N1-9) subtypes. Each virus has on...

  1. Avian influenza prevention and control

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Avian influenza is one of the most important diseases affecting the poultry industry around the world. Avian Influenza virus (AIV) has a broad host range in birds and mammals, although the natural reservoir is considered to be in wild birds where it typically causes an asymptomatic to mild infectio...

  2. Influenza SIRS with Minimal Pneumonitis

    PubMed Central

    Erramilli, Shruti; Mannam, Praveen; Manthous, Constantine A.

    2016-01-01

    Although systemic inflammatory response syndrome (SIRS) is a known complication of severe influenza pneumonia, it has been reported very rarely in patients with minimal parenchymal lung disease. We here report a case of severe SIRS, anasarca, and marked vascular phenomena with minimal or no pneumonitis. This case highlights that viruses, including influenza, may cause vascular dysregulation causing SIRS, even without substantial visceral organ involvement.

  3. Avian influenza: Vaccination and control

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Avian influenza (AI) is a viral disease of poultry that remains an economic threat to commercial poultry throughout the world by negatively impacting animal health and trade. Strategies to control avian influenza (AI) virus are developed to prevent, manage or eradicate the virus from the country, re...

  4. Avian influenza: Current world situation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The human pandemic H1N1 (pH1N1) virus had its origin with animal influenza viruses, likely through a reassortment event between a North American swine influenza virus and another unidentified virus. The first turkey flock to be diagnosed with pH1N1 occurred in Chile, in August 2009. The flock suff...

  5. HAEMOPHILUS INFLUENZA DISEASES SURVEILLANCE SYSTEM

    EPA Science Inventory

    The Haemophilus Influenzae System at NIP compiles information on all U.S. Haemophilus influenzae invasive disease cases reported to CDC via NETSS since 1991 (managed by EPO and NIP), or via active surveillance in several locales since 1989 (managed by NCIP). Information collected...

  6. Optimisation of the formulation and of the technological process of egg-based products for the prevention of Salmonella enteritidis survival and growth.

    PubMed

    Guerzoni, Maria Elisabetta; Vannini, Lucia; Lanciotti, Rosalba; Gardini, Fausto

    2002-03-01

    The aim of this work was to study the survival of Salmonella enteritidis after a pressure treatment in relation to compositive variables (NaCl content, pH), both in model and real systems, the latter consisting in an egg-based mayonnaise type product. Moreover, the fate of the surviving cells of S. enteritidis has been monitored during storage at 10 degrees C and the growth or death parameters have been calculated and modelled in relation to pH, NaCl concentration of the medium and entity of the pressure treatment applied. The modelling of the effects of the environmental factors on the treatment effectiveness indicated that the salt content and pH displayed a synergistic effect with pressure, whose extent was higher in the mayonnaise based products than in BHI. In fact, while in the model systems the cell recovery and growth during the subsequent incubation at 10 degrees C was allowed in many combinations of the Central Composite Design, in the real systems no recovery or growth of S. enteritidis were observed. This viability loss, which was maximum at pH 4.00 or 2% NaCl, could not be attributed merely to the interactions of such variables, but probably involves the naturally occurring antimicrobial enzymes of the raw material, whose activity can be enhanced by the pressure treatment. PMID:11934044

  7. Novel vaccines against influenza viruses

    PubMed Central

    Kang, Sang-Moo; Song, Jae-Min; Compans, Richard W.

    2011-01-01

    Killed and live attenuated influenza virus vaccines are effective in preventing and curbing the spread of influenza epidemics when the strains present in the vaccines are closely matched with the predicted epidemic strains. These vaccines are primarily targeted to induce immunity to the variable major target antigen, hemagglutinin (HA) of influenza virus. However, current vaccines are not effective in preventing the emergence of new pandemic or highly virulent viruses. New approaches are being investigated to develop universal influenza virus vaccines as well as to apply more effective vaccine delivery methods. Conserved vaccine targets including the influenza M2 ion channel protein and HA stalk domains are being developed using recombinant technologies to improve the level of cross protection. In addition, recent studies provide evidence that vaccine supplements can provide avenues to further improve current vaccination. PMID:21968298

  8. Improving pandemic influenza risk assessment

    PubMed Central

    Russell, Colin A; Kasson, Peter M; Donis, Ruben O; Riley, Steven; Dunbar, John; Rambaut, Andrew; Asher, Jason; Burke, Stephen; Davis, C Todd; Garten, Rebecca J; Gnanakaran, Sandrasegaram; Hay, Simon I; Herfst, Sander; Lewis, Nicola S; Lloyd-Smith, James O; Macken, Catherine A; Maurer-Stroh, Sebastian; Neuhaus, Elizabeth; Parrish, Colin R; Pepin, Kim M; Shepard, Samuel S; Smith, David L; Suarez, David L; Trock, Susan C; Widdowson, Marc-Alain; George, Dylan B; Lipsitch, Marc; Bloom, Jesse D

    2014-01-01

    Assessing the pandemic risk posed by specific non-human influenza A viruses is an important goal in public health research. As influenza virus genome sequencing becomes cheaper, faster, and more readily available, the ability to predict pandemic potential from sequence data could transform pandemic influenza risk assessment capabilities. However, the complexities of the relationships between virus genotype and phenotype make such predictions extremely difficult. The integration of experimental work, computational tool development, and analysis of evolutionary pathways, together with refinements to influenza surveillance, has the potential to transform our ability to assess the risks posed to humans by non-human influenza viruses and lead to improved pandemic preparedness and response. DOI: http://dx.doi.org/10.7554/eLife.03883.001 PMID:25321142

  9. Improving pandemic influenza risk assessment.

    PubMed

    Russell, Colin A; Kasson, Peter M; Donis, Ruben O; Riley, Steven; Dunbar, John; Rambaut, Andrew; Asher, Jason; Burke, Stephen; Davis, C Todd; Garten, Rebecca J; Gnanakaran, Sandrasegaram; Hay, Simon I; Herfst, Sander; Lewis, Nicola S; Lloyd-Smith, James O; Macken, Catherine A; Maurer-Stroh, Sebastian; Neuhaus, Elizabeth; Parrish, Colin R; Pepin, Kim M; Shepard, Samuel S; Smith, David L; Suarez, David L; Trock, Susan C; Widdowson, Marc-Alain; George, Dylan B; Lipsitch, Marc; Bloom, Jesse D

    2014-01-01

    Assessing the pandemic risk posed by specific non-human influenza A viruses is an important goal in public health research. As influenza virus genome sequencing becomes cheaper, faster, and more readily available, the ability to predict pandemic potential from sequence data could transform pandemic influenza risk assessment capabilities. However, the complexities of the relationships between virus genotype and phenotype make such predictions extremely difficult. The integration of experimental work, computational tool development, and analysis of evolutionary pathways, together with refinements to influenza surveillance, has the potential to transform our ability to assess the risks posed to humans by non-human influenza viruses and lead to improved pandemic preparedness and response. PMID:25321142

  10. Pandemic Influenza's 500th Anniversary

    PubMed Central

    Morens, David M.; Taubenberger, Jeffery K.; Folkers, Gregory K.; Fauci, Anthony S.

    2010-01-01

    It is impossible to know with certainty the first time that an influenza virus infected humans or when the first influenza pandemic occurred. However, many historians agree that the year 1510 a.d.—500 years ago—marks the first recognition of pandemic influenza. On this significant anniversary it is timely to ask: what were the circumstances surrounding the emergence of the 1510 pandemic, and what have we learned about this important disease over the subsequent five centuries?We conclude that in recent decades significant progress has been made in diagnosis, prevention, control, and treatment of influenza. It seems likely that, in the foreseeable future, we may be able to greatly reduce the burden of influenza pandemics with improved vaccines and other scientific and public health approaches. PMID:21067353

  11. Invasive Disease Caused by Nontypeable Haemophilus influenzae

    PubMed Central

    de Jonge, Marien I.

    2015-01-01

    The incidence of severe Haemophilus influenza infections, such as sepsis and meningitis, has declined substantially since the introduction of the H. influenzae serotype b vaccine. However, the H. influenzae type b vaccine fails to protect against nontypeable H. influenzae strains, which have become increasingly frequent causes of invasive disease, especially among children and the elderly. We summarize recent literature supporting the emergence of invasive nontypeable H. influenzae and describe mechanisms that may explain its increasing prevalence over the past 2 decades. PMID:26407156

  12. DNA Vaccine that Targets Hemagglutinin to MHC Class II Molecules Rapidly Induces Antibody-Mediated Protection against Influenza

    PubMed Central

    Mjaaland, Siri; Roux, Kenneth H.; Fredriksen, Agnete Brunsvik

    2013-01-01

    New influenza A viruses with pandemic potential periodically emerge due to viral genomic reassortment. In the face of pandemic threats, production of conventional egg-based vaccines is time consuming and of limited capacity. We have developed in this study a novel DNA vaccine in which viral hemagglutinin (HA) is bivalently targeted to MHC class II (MHC II) molecules on APCs. Following DNA vaccination, transfected cells secreted vaccine proteins that bound MHC II on APCs and initiated adaptive immune responses. A single DNA immunization induced within 8 d protective levels of strain-specific Abs and also cross-reactive T cells. During the Mexican flu pandemic, a targeted DNA vaccine (HA from A/California/07/2009) was generated within 3 wk after the HA sequences were published online. These results suggest that MHC II–targeted DNA vaccines could play a role in situations of pandemic threats. The vaccine principle should be extendable to other infectious diseases. PMID:23956431

  13. Quadrivalent influenza vaccine: a new opportunity to reduce the influenza burden.

    PubMed

    Tisa, V; Barberis, I; Faccio, V; Paganino, C; Trucchi, C; Martini, M; Ansaldi, F

    2016-01-01

    Influenza illness is caused by influenza A and influenza B strains. Although influenza A viruses are perceived to carry greater risk because they account for the majority of influenza cases in most seasons and have been responsible for influenza pandemics, influenza B viruses also impose a substantial public health burden, particularly among children and at-risk subjects. Furthermore, since the 2001-2002 influenza season, both influenza B lineages, B/Victoria-like viruses and B/Yamagata-like viruses have co-circulated in Europe. The conventional trivalent influenza vaccines have shown a limited ability to induce effective protection when major or minor mismatches between the influenza B vaccine component and circulating strains occur. For this reason, the inclusion of a second B strain in influenza vaccines may help to overcome the well-known difficulties of predicting the circulating B lineage and choosing the influenza B vaccine component. Two quadrivalent influenza vaccines, a live-attenuated quadrivalent influenza vaccine (Q/LAIV) and a split inactivated quadrivalent influenza vaccine (I/QIV), were first licensed in the US in 2012. Since their introduction, models simulating the inclusion of QIV in influenza immunization programs have demonstrated the substantial health benefits, in terms of reducing the number of influenza cases, their complications and mortality. In the near future, evaluations from simulation models should be confirmed by effectiveness studies in the field, and more costeffectiveness analyses should be conducted in order to verify the expected benefits. PMID:27346937

  14. Avian influenza and pandemic influenza preparedness in Hong Kong.

    PubMed

    Lam, Ping Yan

    2008-06-01

    Avian influenza A H5N1 continues to be a major threat to global public health as it is a likely candidate for the next influenza pandemic. To protect public health and avert potential disruption to the economy, the Hong Kong Special Administrative Region Government has committed substantial effort in preparedness for avian and pandemic influenza. Public health infrastructures for emerging infectious diseases have been developed to enhance command, control and coordination of emergency response. Strategies against avian and pandemic influenza are formulated to reduce opportunities for human infection, detect pandemic influenza timely, and enhance emergency preparedness and response capacity. Key components of the pandemic response include strengthening disease surveillance systems, updating legislation on infectious disease prevention and control, enhancing traveller health measures, building surge capacity, maintaining adequate pharmaceutical stockpiles, and ensuring business continuity during crisis. Challenges from avian and pandemic influenza are not to be underestimated. Implementing quarantine and social distancing measures to contain or mitigate the spread of pandemic influenza is problematic in a highly urbanised city like Hong Kong as they involved complex operational and ethical issues. Sustaining effective risk communication campaigns during interpandemic times is another challenge. Being a member of the global village, Hong Kong is committed to contributing its share of efforts and collaborating with health authorities internationally in combating our common public health enemy. PMID:18618061

  15. Antiviral susceptibility of influenza viruses isolated from patients pre- and post-administration of favipiravir.

    PubMed

    Takashita, Emi; Ejima, Miho; Ogawa, Rie; Fujisaki, Seiichiro; Neumann, Gabriele; Furuta, Yousuke; Kawaoka, Yoshihiro; Tashiro, Masato; Odagiri, Takato

    2016-08-01

    Favipiravir, a viral RNA-dependent RNA polymerase inhibitor, has recently been approved in Japan for influenza pandemic preparedness. Here, we conducted a cell-based screening system to evaluate the susceptibility of influenza viruses to favipiravir. In this assay, the antiviral activity of favipiravir is determined by inhibition of virus-induced cytopathic effect, which can be measured by using a colorimetric cell proliferation assay. To demonstrate the robustness of the assay, we compared the favipiravir susceptibilities of neuraminidase (NA) inhibitor-resistant influenza A(H1N1)pdm09, A(H3N2), A(H7N9) and B viruses and their sensitive counterparts. No significant differences in the favipiravir susceptibilities were found between NA inhibitor-resistant and sensitive viruses. We, then, examined the antiviral susceptibility of 57 pairs of influenza viruses isolated from patients pre- and post-administration of favipiravir in phase 3 clinical trials. We found that there were no viruses with statistically significant reduced susceptibility to favipiravir or NA inhibitors, although two of 20 paired A(H1N1)pdm09, one of 17 paired A(H3N2) and one of 20 paired B viruses possessed amino acid substitutions in the RNA-dependent RNA polymerase subunits, PB1, PB2 and PA, after favipiravir administration. This is the first report on the antiviral susceptibility of influenza viruses isolated from patients after favipiravir treatment. PMID:27321665

  16. Quercetin as an Antiviral Agent Inhibits Influenza A Virus (IAV) Entry

    PubMed Central

    Wu, Wenjiao; Li, Richan; Li, Xianglian; He, Jian; Jiang, Shibo; Liu, Shuwen; Yang, Jie

    2015-01-01

    Influenza A viruses (IAVs) cause seasonal pandemics and epidemics with high morbidity and mortality, which calls for effective anti-IAV agents. The glycoprotein hemagglutinin of influenza virus plays a crucial role in the initial stage of virus infection, making it a potential target for anti-influenza therapeutics development. Here we found that quercetin inhibited influenza infection with a wide spectrum of strains, including A/Puerto Rico/8/34 (H1N1), A/FM-1/47/1 (H1N1), and A/Aichi/2/68 (H3N2) with half maximal inhibitory concentration (IC50) of 7.756 ± 1.097, 6.225 ± 0.467, and 2.738 ± 1.931 μg/mL, respectively. Mechanism studies identified that quercetin showed interaction with the HA2 subunit. Moreover, quercetin could inhibit the entry of the H5N1 virus using the pseudovirus-based drug screening system. This study indicates that quercetin showing inhibitory activity in the early stage of influenza infection provides a future therapeutic option to develop effective, safe and affordable natural products for the treatment and prophylaxis of IAV infections. PMID:26712783

  17. [Influenza vaccine and adjuvant].

    PubMed

    Nakayama, Tetsuo

    2011-01-01

    Adjuvant is originated from the Latin word "adjuvare" which means "help" in English to enhance the immunological responses when given together with antigens. The beginning of adjuvant was mineral oil which enhanced the immune response when it was given with inactivated Salmonella typhimurium. Aluminium salt was used to precipitate diphtheria toxoid and increased level of antibody response was demonstrated when administered with alum-precipitated antigens. Since 1930, aluminium salt has been used as DTaP (diphtheria-tetanus-acellular pertussis vaccine) adjuvant. Many candidates were tested for adjuvant activity but only aluminum salt is allowed to use for human vaccines. New adjuvant MF59, oil-in-water emulsion type, was developed for influenza vaccine for elderly (Fluad) and series of AS adjuvant are used for hepatitis B, pandemic flue, and human papiloma virus vaccines. Oil-adjuvanted influenza pandemic vaccines induced higher antibody response than alum-adjuvanted vaccine with higher incidence of adverse events, especially for local reactions. Alum-adjuvanted whole virion inactivated H5N1 vaccine was developed in Japan, and it induced relatively well immune responses in adults. When it applied for children, febrile reaction was noted in approximately 60% of the subjects, with higher antibodies. Recent investigation on innate immunity demonstrates that adjuvant activity is initiated from the stimulation on innate immunity and/or inflammasome, resulting in cytokine induction and antigen uptake by monocytes and macrophages. The probable reason for high incidence of febrile reaction should be investigated to develop a safe and effective influenza vaccine. PMID:22129866

  18. Toward improved influenza control through vaccination.

    PubMed

    Falleiros Arlant, Luiza Helena; Ferro Bricks, Lucia

    2015-04-01

    In August 27/2014, SLIPE organized the Master Class "Towards improved influenza control through vaccination", a panel with international influenza experts who shared their understanding of the disease and the control measures available, focusing on the most recent information about this serious diseases. In this report Dr Falleiros and Dr Bricks summarized the following topics: Global influenza epidemiology, presented by Dr Puig-Barbera; Influenza vaccine recommendations and coverage in Latin American countries, presented by Dr Bricks; Influenza vaccines efficacy and effectiveness, presented by Dr Fedson: Influenza burden ;md rational for prevention in children, presented by Dr Muiioz; Influenza burden in pregnancy, presented by Dr Ribeiro; Influenza vaccination in health care workers, presented by Dr Macias; Influenza vaccination in the elderly, presented by Dr Ribeiro; Rational to increase vaccination coverage rates Global Influenza Hospital Surveillance Network, presented by Dr Puig-Barbera; Influenza B epidemiology and vaccine strain mismatch in Latin American Region, presented by Dr Bricks; Modeling for quadrivalent influenza vaccines impact, presented by Dr Blank; Rational for quadrivalent influenza vaccines and the clinical development of QIV s, presented by Dr Desauziers and Modelling quadrivalent influenza vaccines impact, presented by Dr Blank. PMID:26065453

  19. Avian influenza in Mexico.

    PubMed

    Villarreal, C

    2009-04-01

    The outbreak of highly pathogenic avian influenza (HPAI) H5N2 in Mexico in 1994 led to a clear increase in biosecurity measures and improvement of intensive poultry production systems. The control and eradication measures implemented were based on active surveillance, disease detection, depopulation of infected farms and prevention of possible contacts (identified by epidemiological investigations), improvement of biosecurity measures, and restriction of the movement of live birds, poultry products, by-products and infected material. In addition, Mexico introduced a massive vaccination programme, which resulted in the eradication of HPAI in a relatively short time in two affected areas that had a high density of commercial poultry. PMID:19618630

  20. Household Transmission of Influenza Virus.

    PubMed

    Tsang, Tim K; Lau, Lincoln L H; Cauchemez, Simon; Cowling, Benjamin J

    2016-02-01

    Human influenza viruses cause regular epidemics and occasional pandemics with a substantial public health burden. Household transmission studies have provided valuable information on the dynamics of influenza transmission. We reviewed published studies and found that once one household member is infected with influenza, the risk of infection in a household contact can be up to 38%, and the delay between onset in index and secondary cases is around 3 days. Younger age was associated with higher susceptibility. In the future, household transmission studies will provide information on transmission dynamics, including the correlation of virus shedding and symptoms with transmission, and the correlation of new measures of immunity with protection against infection. PMID:26612500

  1. Spatiotemporal characteristics of pandemic influenza

    PubMed Central

    2014-01-01

    Background Prediction of timing for the onset and peak of an influenza pandemic is of vital importance for preventive measures. In order to identify common spatiotemporal patterns and climate influences for pandemics in Sweden we have studied the propagation in space and time of A(H1N1)pdm09 (10,000 laboratory verified cases), the Asian Influenza 1957–1958 (275,000 cases of influenza-like illness (ILI), reported by local physicians) and the Russian Influenza 1889–1890 (32,600 ILI cases reported by physicians shortly after the end of the outbreak). Methods All cases were geocoded and analysed in space and time. Animated video sequences, showing weekly incidence per municipality and its geographically weighted mean (GWM), were created to depict and compare the spread of the pandemics. Daily data from 1957–1958 on temperature and precipitation from 39 weather stations were collected and analysed with the case data to examine possible climatological effects on the influenza dissemination. Results The epidemic period lasted 11 weeks for the Russian Influenza, 10 weeks for the Asian Influenza and 9 weeks for the A(H1N1)pdm09. The Russian Influenza arrived in Sweden during the winter and was immediately disseminated, while both the Asian Influenza and the A(H1N1)pdm09 arrived during the spring. They were seeded over the country during the summer, but did not peak until October-November. The weekly GWM of the incidence moved along a line from southwest to northeast for the Russian and Asian Influenza but northeast to southwest for the A(H1N1)pdm09. The local epidemic periods of the Asian Influenza were preceded by falling temperature in all but one of the locations analysed. Conclusions The power of spatiotemporal analysis and modeling for pandemic spread was clearly demonstrated. The epidemic period lasted approximately 10 weeks for all pandemics. None of the pandemics had its epidemic period before late autumn. The epidemic period of the Asian Influenza was

  2. Growth determinants for H5N1 influenza vaccine seed viruses in MDCK cells.

    PubMed

    Murakami, Shin; Horimoto, Taisuke; Mai, Le Quynh; Nidom, Chairul A; Chen, Hualan; Muramoto, Yukiko; Yamada, Shinya; Iwasa, Ayaka; Iwatsuki-Horimoto, Kiyoko; Shimojima, Masayuki; Iwata, Akira; Kawaoka, Yoshihiro

    2008-11-01

    H5N1 influenza A viruses are exacting a growing human toll, with more than 240 fatal cases to date. In the event of an influenza pandemic caused by these viruses, embryonated chicken eggs, which are the approved substrate for human inactivated-vaccine production, will likely be in short supply because chickens will be killed by these viruses or culled to limit the worldwide spread of the infection. The Madin-Darby canine kidney (MDCK) cell line is a promising alternative candidate substrate because it supports efficient growth of influenza viruses compared to other cell lines. Here, we addressed the molecular determinants for growth of an H5N1 vaccine seed virus in MDCK cells, revealing the critical responsibility of the Tyr residue at position 360 of PB2, the considerable requirement for functional balance between hemagglutinin (HA) and neuraminidase (NA), and the partial responsibility of the Glu residue at position 55 of NS1. Based on these findings, we produced a PR8/H5N1 reassortant, optimized for this cell line, that derives all of its genes for its internal proteins from the PR8(UW) strain except for the NS gene, which derives from the PR8(Cambridge) strain; its N1 NA gene, which has a long stalk and derives from an early H5N1 strain; and its HA gene, which has an avirulent-type cleavage site sequence and is derived from a circulating H5N1 virus. Our findings demonstrate the importance and feasibility of a cell culture-based approach to producing seed viruses for inactivated H5N1 vaccines that grow robustly and in a timely, cost-efficient manner as an alternative to egg-based vaccine production. PMID:18768983

  3. Influenza A Virus Polymerase Is a Site for Adaptive Changes during Experimental Evolution in Bat Cells

    PubMed Central

    Poole, Daniel S.; Yú, Shuǐqìng; Caì, Yíngyún; Dinis, Jorge M.; Müller, Marcel A.; Jordan, Ingo; Friedrich, Thomas C.; Kuhn, Jens H.

    2014-01-01

    ABSTRACT The recent identification of highly divergent influenza A viruses in bats revealed a new, geographically dispersed viral reservoir. To investigate the molecular mechanisms of host-restricted viral tropism and the potential for transmission of viruses between humans and bats, we exposed a panel of cell lines from bats of diverse species to a prototypical human-origin influenza A virus. All of the tested bat cell lines were susceptible to influenza A virus infection. Experimental evolution of human and avian-like viruses in bat cells resulted in efficient replication and created highly cytopathic variants. Deep sequencing of adapted human influenza A virus revealed a mutation in the PA polymerase subunit not previously described, M285K. Recombinant virus with the PA M285K mutation completely phenocopied the adapted virus. Adaptation of an avian virus-like virus resulted in the canonical PB2 E627K mutation that is required for efficient replication in other mammals. None of the adaptive mutations occurred in the gene for viral hemagglutinin, a gene that frequently acquires changes to recognize host-specific variations in sialic acid receptors. We showed that human influenza A virus uses canonical sialic acid receptors to infect bat cells, even though bat influenza A viruses do not appear to use these receptors for virus entry. Our results demonstrate that bats are unique hosts that select for both a novel mutation and a well-known adaptive mutation in the viral polymerase to support replication. IMPORTANCE Bats constitute well-known reservoirs for viruses that may be transferred into human populations, sometimes with fatal consequences. Influenza A viruses have recently been identified in bats, dramatically expanding the known host range of this virus. Here we investigated the replication of human influenza A virus in bat cell lines and the barriers that the virus faces in this new host. Human influenza A and B viruses infected cells from geographically and

  4. Protection against multiple subtypes of influenza viruses by virus-like particle vaccines based on a hemagglutinin conserved epitope.

    PubMed

    Chen, Shaoheng; Zheng, Dan; Li, Changgui; Zhang, Wenjie; Xu, Wenting; Liu, Xueying; Fang, Fang; Chen, Ze

    2015-01-01

    We selected the conserved sequence in the stalk region of influenza virus hemagglutinin (HA) trimmer, the long alpha helix (LAH), as the vaccine candidate sequence, and inserted it into the major immunodominant region (MIR) of hepatitis B virus core protein (HBc), and, by using the E. coli expression system, we prepared a recombinant protein vaccine LAH-HBc in the form of virus-like particles (VLP). Intranasal immunization of mice with this LAH-HBc VLP plus cholera toxin B subunit with 0.2% of cholera toxin (CTB(*)) adjuvant could effectively elicit humoral and cellular immune responses and protect mice against a lethal challenge of homologous influenza viruses (A/Puerto Rico/8/1934 (PR8) (H1N1)). In addition, passage of the immune sera containing specific antibodies to naïve mice rendered them resistant against a lethal homologous challenge. Immunization with LAH-HBc VLP vaccine plus CTB(*) adjuvant could also fully protect mice against a lethal challenge of the 2009 pandemic H1N1 influenza virus or the avian H9N2 virus and could partially protect mice against a lethal challenge of the avian H5N1 influenza virus. This study demonstrated that the LAH-HBc VLP vaccine based on a conserved sequence of the HA trimmer stalk region is a promising candidate vaccine for developing a universal influenza vaccine against multiple influenza viruses infections. PMID:25767809

  5. Prevention and management of influenza in pregnancy.

    PubMed

    Beigi, Richard H

    2014-12-01

    Influenza infections are an important global source of morbidity and mortality. Pregnant and postpartum women are at increased risk for serious disease, related complications, and death from influenza infection. This increased risk is thought to be mostly caused by the altered physiologic and immunologic specifics of pregnancy. The morbidity of influenza infection during pregnancy is compounded by the potential for adverse obstetric, fetal, and neonatal outcomes. Importantly, influenza vaccination to prevent or minimize the severity of influenza infection during pregnancy (and the neonatal period) is recommended for all women who are or will be pregnant during influenza season. PMID:25454989

  6. Influenza virus hemagglutinin as a vaccine antigen produced in bacteria.

    PubMed

    Sączyńska, Violetta

    2014-01-01

    Recombinant subunit vaccines based on hemagglutinin proteins produced in bacteria (bacterial HAs) are promising candidates for enhancing the supply of vaccines against influenza, especially for a pandemic. Over 20 years after the failure to obtain the antigen with native HA characteristics in the early 1980's, there are increasing data on successful production of HA proteins in bacteria. The vast majority of bacterial HAs have been based on the HA1 subunit of HA expressed separately or as a component of conjugate vaccines, but those based on the ectodomain and the HA2 subunit have also been reported. The most of HAs have been efficiently expressed as insoluble aggregates called inclusion bodies. Refolded and purified proteins were extensively studied for structure, the ability to bind to sialic acid-containing receptors, antigenicity, immunogenicity and efficacy. The results from these studies contradict the view that glycosylation determines the correct structure of the hemagglutinin, as they proved that bacterial HAs can be valuable vaccine antigens when appropriate folding and purification methods are applied to rationally designed proteins. The best evidence for success in bacterial production of protective HA is that vaccines based on proprietary Toll-like Receptor (VaxInnate) and bacteriophage Qβ-VLPs (Cytos Biotechnology) technologies have been advanced to clinical studies. PMID:25195143

  7. National surveillance for influenza and influenza-like illness in Vietnam, 2006-2010.

    PubMed

    Nguyen, Yen T; Graitcer, Samuel B; Nguyen, Tuan H; Tran, Duong N; Pham, Tho D; Le, Mai T Q; Tran, Huu N; Bui, Chien T; Dang, Dat T; Nguyen, Long T; Uyeki, Timothy M; Dennis, David; Kile, James C; Kapella, Bryan K; Iuliano, A D; Widdowson, Marc-Alain; Nguyen, Hien T

    2013-09-13

    Influenza virus infections result in considerable morbidity and mortality both in the temperate and tropical world. Influenza surveillance over multiple years is important to determine the impact and epidemiology of influenza and to develop a national vaccine policy, especially in countries developing influenza vaccine manufacturing capacity, such as Vietnam. We conducted surveillance of influenza and influenza-like illness in Vietnam through the National Influenza Surveillance System during 2006-2010. At 15 sentinel sites, the first two patients presenting each weekday with influenza-like illness (ILI), defined as fever and cough and/or sore throat with illness onset within 3 days, were enrolled and throat specimens were collected and tested for influenza virus type and influenza A subtype by RT-PCR. De-identified demographic and provider reported subsequent hospitalization information was collected on each patient. Each site also collected information on the total number of patients with influenza-like illness evaluated per week. Of 29,804 enrolled patients presenting with influenza-like illness, 6516 (22%) were influenza positive. Of enrolled patients, 2737 (9.3%) were reported as subsequently hospitalized; of the 2737, 527 (19%) were influenza positive. Across all age groups with ILI, school-aged children had the highest percent of influenza infection (29%) and the highest percent of subsequent hospitalizations associated with influenza infection (28%). Influenza viruses co-circulated throughout most years in Vietnam during 2006-2010 and often reached peak levels multiple times during a year, when >20% of tests were influenza positive. Influenza is an important cause of all influenza-like illness and provider reported subsequent hospitalization among outpatients in Vietnam, especially among school-aged children. These findings may have important implications for influenza vaccine policy in Vietnam. PMID:23911781

  8. New aspects of influenza viruses.

    PubMed Central

    Shaw, M W; Arden, N H; Maassab, H F

    1992-01-01

    Influenza virus infections continue to cause substantial morbidity and mortality with a worldwide social and economic impact. The past five years have seen dramatic advances in our understanding of viral replication, evolution, and antigenic variation. Genetic analyses have clarified relationships between human and animal influenza virus strains, demonstrating the potential for the appearance of new pandemic reassortants as hemagglutinin and neuraminidase genes are exchanged in an intermediate host. Clinical trials of candidate live attenuated influenza virus vaccines have shown the cold-adapted reassortants to be a promising alternative to the currently available inactivated virus preparations. Modern molecular techniques have allowed serious consideration of new approaches to the development of antiviral agents and vaccines as the functions of the viral genes and proteins are further elucidated. The development of techniques whereby the genes of influenza viruses can be specifically altered to investigate those functions will undoubtedly accelerate the pace at which our knowledge expands. PMID:1310439

  9. Influenza Prevention: Information for Travelers

    MedlinePlus

    ... season and are traveling to parts of the world where influenza activity is ongoing should get a ... have been circulating in other parts of the world. People should get vaccinated at least 2 weeks ...

  10. Genetic Analyses of an H3N8 Influenza Virus Isolate, Causative Strain of the Outbreak of Equine Influenza at the Kanazawa Racecourse in Japan in 2007.

    PubMed

    Ito, Mika; Nagai, Makoto; Hayakawa, Yuji; Komae, Hirofumi; Murakami, Naruto; Yotsuya, Syouichi; Asakura, Shingo; Sakoda, Yoshihiro; Kida, Hiroshi

    2008-09-01

    In August 2007, an outbreak of equine influenza occurred among vaccinated racehorses with Japanese commercial equine influenza vaccine at Kanazawa Racecourse in Ishikawa prefecture in Japan. Apparent symptoms were pyrexia (38.2-41.0 degrees C) and nasal discharge with or without coughing, although approximately half of the infected horses were subclinical. All horses had been shot with a vaccine that contained two inactivated H3N8 influenza virus strains [A/equine/La Plata/93 (La Plata/93) of American lineage and A/equine/Avesta/93 (Avesta/93) of European lineage] and an H7N7 strain (A/equine/Newmarket/1/77). Influenza virus, A/equine/Kanazawa/1/2007 (H3N8) (Kanazawa/07), was isolated from one of the nasal swab samples of diseased horses. Phylogenetic analysis indicated that Kanazawa/07 was classified into the American sublineage Florida. In addition, four amino acid substitutions were found in the antigenic sites B and E in the HA1 subunit protein of Kanazawa/07 in comparison with that of La Plata/93. Hemagglutination-inhibition (HI) test using 16 serum samples from recovering horses revealed that 1.4- to 8-fold difference in titers between Kanazawa/07 and either of the vaccine strains. The present findings suggest that Japanese commercial inactivated vaccine contributed to reducing the morbidity rate and manifestation of the clinical signs of horses infected with Kanazawa/07 that may be antigenically different from the vaccine strains. PMID:18840963

  11. Influenza vaccines: an Asia-Pacific perspective.

    PubMed

    Jennings, Lance C

    2013-11-01

    This article provides an overview of some aspects of seasonal, pre-pandemic and pandemic influenza vaccines and initiatives aimed to increase influenza vaccine use within the Asia-Pacific region. Expanding the use of influenza vaccines in the Asia-Pacific region faces many challenges. Despite the recent regional history for the emergence of novel viruses, SARS, the H5N1 and H7N9, and the generation of and global seeding of seasonal influenza viruses and initiatives by WHO and other organisations to expand influenza awareness, the use of seasonal influenza vaccines remains low. The improvement in current vaccine technologies with the licensing of quadrivalent, live-attenuated, cell culture-based, adjuvanted and the first recombinant influenza vaccine is an important step. The development of novel influenza vaccines able to provide improved protection and with improved manufacturing capacity is also advancing rapidly. However, of ongoing concern are seasonal influenza impact and the low use of seasonal influenza vaccines in the Asia-Pacific region. Improved influenza control strategies and their implementation in the region are needed. Initiatives by the World Health Organization (WHO), and specifically the Western Pacific Regional Office of WHO, are focusing on consistent vaccine policies and guidelines in countries in the region. The Asian-Pacific Alliance for the Control of Influenza (APACI) is contributing through the coordination of influenza advocacy initiates. PMID:24215381

  12. Avian influenza virus in pregnancy.

    PubMed

    Liu, Shelan; Sha, Jianping; Yu, Zhao; Hu, Yan; Chan, Ta-Chien; Wang, Xiaoxiao; Pan, Hao; Cheng, Wei; Mao, Shenghua; Zhang, Run Ju; Chen, Enfu

    2016-07-01

    The unprecedented epizootic of avian influenza viruses, such as H5N1, H5N6, H7N1 and H10N8, has continued to cause disease in humans in recent years. In 2013, another novel influenza A (H7N9) virus emerged in China, and 30% of those patients died. Pregnant women are particularly susceptible to avian influenza and are more likely to develop severe complications and to die, especially when infection occurs in the middle and late trimesters. Viremia is believed to occur infrequently, and thus vertical transmission induced by avian influenza appears to be rare. However, avian influenza increases the risk of adverse pregnancy outcomes, including spontaneous abortion, preterm birth and fatal distress. This review summarises 39 cases of pregnant women and their fetuses from different countries dating back to 1997, including 11, 15 and 13 infections with H7N9, H5N1 and the 2009 pandemic influenza (H1N1), respectively. We analysed the epidemic features, following the geographical, population and pregnancy trimester distributions; underlying diseases; exposure history; medical timelines; human-to-human transmission; pathogenicity and vertical transmission; antivirus treatments; maternal severity and mortality and pregnancy outcome. The common experiences reported in different countries and areas suggest that early identification and treatment are imperative. In the future, vigilant virologic and epidemiologic surveillance systems should be developed to monitor avian influenza viruses during pregnancy. Furthermore, extensive study on the immune mechanisms should be conducted, as this will guide safe, rational immunomodulatory treatment among this high-risk population. Most importantly, we should develop a universal avian influenza virus vaccine to prevent outbreaks of the different subtypes. Copyright © 2016 John Wiley & Sons, Ltd. PMID:27187752

  13. Emergence of influenza A viruses.

    PubMed Central

    Webby, R J; Webster, R G

    2001-01-01

    Pandemic influenza in humans is a zoonotic disease caused by the transfer of influenza A viruses or virus gene segments from animal reservoirs. Influenza A viruses have been isolated from avian and mammalian hosts, although the primary reservoirs are the aquatic bird populations of the world. In the aquatic birds, influenza is asymptomatic, and the viruses are in evolutionary stasis. The aquatic bird viruses do not replicate well in humans, and these viruses need to reassort or adapt in an intermediate host before they emerge in human populations. Pigs can serve as a host for avian and human viruses and are logical candidates for the role of intermediate host. The transmission of avian H5N1 and H9N2 viruses directly to humans during the late 1990s showed that land-based poultry also can serve between aquatic birds and humans as intermediate hosts of influenza viruses. That these transmission events took place in Hong Kong and China adds further support to the hypothesis that Asia is an epicentre for influenza and stresses the importance of surveillance of pigs and live-bird markets in this area. PMID:11779380

  14. Antigenic properties of a transport-competent influenza HA/HIV Env chimeric protein

    SciTech Connect

    Ye Ling; Sun Yuliang; Lin Jianguo; Bu Zhigao; Wu Qingyang; Jiang, Shibo; Steinhauer, David A.; Compans, Richard W.; Yang Chinglai . E-mail: chyang@emory.edu

    2006-08-15

    The transmembrane subunit (gp41) of the HIV Env glycoprotein contains conserved neutralizing epitopes which are not well-exposed in wild-type HIV Env proteins. To enhance the exposure of these epitopes, a chimeric protein, HA/gp41, in which the gp41 of HIV-1 89.6 envelope protein was fused to the C-terminus of the HA1 subunit of the influenza HA protein, was constructed. Characterization of protein expression showed that the HA/gp41 chimeric proteins were expressed on cell surfaces and formed trimeric oligomers, as found in the HIV Env as well as influenza HA proteins. In addition, the HA/gp41 chimeric protein expressed on the cell surface can also be cleaved into 2 subunits by trypsin treatment, similar to the influenza HA. Moreover, the HA/gp41 chimeric protein was found to maintain a pre-fusion conformation. Interestingly, the HA/gp41 chimeric proteins on cell surfaces exhibited increased reactivity to monoclonal antibodies against the HIV Env gp41 subunit compared with the HIV-1 envelope protein, including the two broadly neutralizing monoclonal antibodies 2F5 and 4E10. Immunization of mice with a DNA vaccine expressing the HA/gp41 chimeric protein induced antibodies against the HIV gp41 protein and these antibodies exhibit neutralizing activity against infection by an HIV SF162 pseudovirus. These results demonstrate that the construction of such chimeric proteins can provide enhanced exposure of conserved epitopes in the HIV Env gp41 and may represent a novel vaccine design strategy for inducing broadly neutralizing antibodies against HIV.

  15. Hemagglutinin of Influenza A Virus Antagonizes Type I Interferon (IFN) Responses by Inducing Degradation of Type I IFN Receptor 1

    PubMed Central

    Xia, Chuan; Vijayan, Madhuvanthi; Pritzl, Curtis J.; Fuchs, Serge Y.; McDermott, Adrian B.

    2015-01-01

    ABSTRACT Influenza A virus (IAV) employs diverse strategies to circumvent type I interferon (IFN) responses, particularly by inhibiting the synthesis of type I IFNs. However, it is poorly understood if and how IAV regulates the type I IFN receptor (IFNAR)-mediated signaling mode. In this study, we demonstrate that IAV induces the degradation of IFNAR subunit 1 (IFNAR1) to attenuate the type I IFN-induced antiviral signaling pathway. Following infection, the level of IFNAR1 protein, but not mRNA, decreased. Indeed, IFNAR1 was phosphorylated and ubiquitinated by IAV infection, which resulted in IFNAR1 elimination. The transiently overexpressed IFNAR1 displayed antiviral activity by inhibiting virus replication. Importantly, the hemagglutinin (HA) protein of IAV was proved to trigger the ubiquitination of IFNAR1, diminishing the levels of IFNAR1. Further, influenza A viral HA1 subunit, but not HA2 subunit, downregulated IFNAR1. However, viral HA-mediated degradation of IFNAR1 was not caused by the endoplasmic reticulum (ER) stress response. IAV HA robustly reduced cellular sensitivity to type I IFNs, suppressing the activation of STAT1/STAT2 and induction of IFN-stimulated antiviral proteins. Taken together, our findings suggest that IAV HA causes IFNAR1 degradation, which in turn helps the virus escape the powerful innate immune system. Thus, the research elucidated an influenza viral mechanism for eluding the IFNAR signaling pathway, which could provide new insights into the interplay between influenza virus and host innate immunity. IMPORTANCE Influenza A virus (IAV) infection causes significant morbidity and mortality worldwide and remains a major health concern. When triggered by influenza viral infection, host cells produce type I interferon (IFN) to block viral replication. Although IAV was shown to have diverse strategies to evade this powerful, IFN-mediated antiviral response, it is not well-defined if IAV manipulates the IFN receptor-mediated signaling

  16. DnaJA1/Hsp40 Is Co-Opted by Influenza A Virus To Enhance Its Viral RNA Polymerase Activity

    PubMed Central

    Cao, Mengmeng; Wei, Candong; Zhao, Lili; Wang, Jingfeng; Jia, Qiannan; Wang, Xue

    2014-01-01

    ABSTRACT The RNA-dependent RNA polymerase (RdRp) of influenza A virus is a heterotrimeric complex composed of the PB1, PB2, and PA subunits. The interplay between host factors and the three subunits of the RdRp is critical to enable viral RNA synthesis to occur in the nuclei of infected cells. In this study, we newly identified host factor DnaJA1, a member of the type I DnaJ/Hsp40 family, acting as a positive regulator for influenza virus replication. We found that DnaJA1 associates with the bPB2 and PA subunits and enhances viral RNA synthesis both in vivo and in vitro. Moreover, DnaJA1 could be translocated from cytoplasm into the nucleus upon influenza virus infection. The translocation of DnaJA1 is specifically accompanied by PB1-PA nuclear import. Interestingly, we observed that the effect of DnaJA1 on viral RNA synthesis is mainly dependent on its C-terminal substrate-binding domain and not on its typical J domain, while the J domain normally mediates the Hsp70-DnaJ interaction required for regulating Hsp70 ATPase activity. Therefore, we propose that DnaJA1 is co-opted by the influenza A virus to enter the nucleus and to enhance its RNA polymerase activity in an Hsp70 cochaperone-independent manner. IMPORTANCE The interplay between host factors and influenza virus RNA polymerase plays a critical role in determining virus pathogenicity and host adaptation. In this study, we newly identified a host protein, DnaJA1/Hsp40, that is co-opted by influenza A virus RNA polymerase to enhance its viral RNA synthesis in the nuclei of infected cells. We found that DnaJA1 associates with both PB2 and PA subunits and translocates into the nucleus along with the nuclear import of the PB1-PA dimer during influenza virus replication. Interestingly, the effect of DnaJA1 is mainly dependent on its C-terminal substrate-binding domain and not on its typical J domain, which is required for its Hsp70 cochaperone function. To our knowledge, this is the first report on a member of the

  17. Novel hemagglutinin-based influenza virus inhibitors

    PubMed Central

    Shen, Xintian; Zhang, Xuanxuan

    2013-01-01

    Influenza virus has caused seasonal epidemics and worldwide pandemics, which caused tremendous loss of human lives and socioeconomics. Nowadays, only two classes of anti-influenza drugs, M2 ion channel inhibitors and neuraminidase inhibitors respectively, are used for prophylaxis and treatment of influenza virus infection. Unfortunately, influenza virus strains resistant to one or all of those drugs emerge frequently. Hemagglutinin (HA), the glycoprotein in influenza virus envelope, plays a critical role in viral binding, fusion and entry processes. Therefore, HA is a promising target for developing anti-influenza drugs, which block the initial entry step of viral life cycle. Here we reviewed recent understanding of conformational changes of HA in protein folding and fusion processes, and the discovery of HA-based influenza entry inhibitors, which may provide more choices for preventing and controlling potential pandemics caused by multi-resistant influenza viruses. PMID:23977436

  18. Influenza Virus Infection of Marine Mammals.

    PubMed

    Fereidouni, Sasan; Munoz, Olga; Von Dobschuetz, Sophie; De Nardi, Marco

    2016-03-01

    Interspecies transmission may play a key role in the evolution and ecology of influenza A viruses. The importance of marine mammals as hosts or carriers of potential zoonotic pathogens such as highly pathogenic H5 and H7 influenza viruses is not well understood. The fact that influenza viruses are some of the few zoonotic pathogens known to have caused infection in marine mammals, evidence for direct transmission of influenza A virus H7N7 subtype from seals to man, transmission of pandemic H1N1 influenza viruses to seals and also limited evidence for long-term persistence of influenza B viruses in seal populations without significant genetic change, makes monitoring of influenza viruses in marine mammal populations worth being performed. In addition, such monitoring studies could be a great tool to better understand the ecology of influenza viruses in nature. PMID:25231137

  19. Variant (Swine Origin) Influenza Viruses in Humans

    MedlinePlus

    ... What's this? Submit Button Past Newsletters Variant Influenza Viruses: Background and CDC Risk Assessment and Reporting Language: ... Background CDC Assessment Reporting Background On Variant Influenza Viruses Swine flu viruses do not normally infect humans. ...

  20. CDC Influenza E-Brief 2015

    MedlinePlus

    ... is a contagious respiratory illness caused by influenza viruses. It can cause mild to severe illness, and ... flu vaccine will protect against the three influenza viruses that surveillance suggests will be most common during ...

  1. Swine Influenza (Swine Flu) in Pigs

    MedlinePlus

    ... in the United States since 2005 Prevention Treatment Influenza Types Seasonal Avian Swine Variant Pandemic Other Get ... Submit Button Past Newsletters Key Facts about Swine Influenza (Swine Flu) in Pigs Language: English Español ...

  2. Avian Influenza A Virus Infections in Humans

    MedlinePlus

    ... Research Making a Candidate Vaccine Virus Related Links Influenza Types Seasonal Avian Swine Variant Pandemic Other Get ... Submit What's this? Submit Button Past Newsletters Avian Influenza A Virus Infections in Humans Language: English Españ ...

  3. Fluorescence biosensor based on CdTe quantum dots for specific detection of H5N1 avian influenza virus

    NASA Astrophysics Data System (ADS)

    Hoa Nguyen, Thi; Dieu Thuy Ung, Thi; Hien Vu, Thi; Tran, Thi Kim Chi; Quyen Dong, Van; Khang Dinh, Duy; Liem Nguyen, Quang

    2012-09-01

    This report highlights the fabrication of fluorescence biosensors based on CdTe quantum dots (QDs) for specific detection of H5N1 avian influenza virus. The core biosensor was composed of (i) the highly luminescent CdTe/CdS QDs, (ii) chromatophores extracted from bacteria Rhodospirillum rubrum, and (iii) the antibody of β-subunit. This core part was linked to the peripheral part of the biosensor via a biotin–streptavidin–biotin bridge and finally connected to the H5N1 antibody to make it ready for detecting H5N1 avian influenza virus. Detailed studies of each constituent were performed showing the image of QDs-labeled chromatophores under optical microscope, proper photoluminescence (PL) spectra of CdTe/CdS QDs, chromatophores and the H5N1 avian influenza viruses.

  4. 28 CFR 51.6 - Political subunits.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 28 Judicial Administration 2 2012-07-01 2012-07-01 false Political subunits. 51.6 Section 51.6 Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) PROCEDURES FOR THE ADMINISTRATION OF SECTION 5 OF THE VOTING RIGHTS ACT OF 1965, AS AMENDED General Provisions § 51.6 Political subunits. All...

  5. 28 CFR 51.6 - Political subunits.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Political subunits. 51.6 Section 51.6 Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) PROCEDURES FOR THE ADMINISTRATION OF SECTION 5 OF THE VOTING RIGHTS ACT OF 1965, AS AMENDED General Provisions § 51.6 Political subunits. All...

  6. 28 CFR 51.6 - Political subunits.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 28 Judicial Administration 2 2011-07-01 2011-07-01 false Political subunits. 51.6 Section 51.6 Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) PROCEDURES FOR THE ADMINISTRATION OF SECTION 5 OF THE VOTING RIGHTS ACT OF 1965, AS AMENDED General Provisions § 51.6 Political subunits. All...

  7. 28 CFR 51.6 - Political subunits.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 28 Judicial Administration 2 2013-07-01 2013-07-01 false Political subunits. 51.6 Section 51.6 Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) PROCEDURES FOR THE ADMINISTRATION OF SECTION 5 OF THE VOTING RIGHTS ACT OF 1965, AS AMENDED General Provisions § 51.6 Political subunits. All...

  8. 28 CFR 51.6 - Political subunits.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 28 Judicial Administration 2 2014-07-01 2014-07-01 false Political subunits. 51.6 Section 51.6 Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) PROCEDURES FOR THE ADMINISTRATION OF SECTION 5 OF THE VOTING RIGHTS ACT OF 1965, AS AMENDED General Provisions § 51.6 Political subunits. All...

  9. Influenza in Canada geese.

    PubMed

    Winkler, W G; Trainer, D O; Easterday, B C

    1972-01-01

    The role of wild avian species in the natural history of influenza is unknown. A serological study was carried out to ascertain the prevalence, distribution, and types of influenza antibody in several wild Canada goose populations. Geese were trapped and blood samples were obtained in each of 4 consecutive years, 1966-69. Antibody to influenzavirus was found in 66 (4.7%) of the 1 401 Canada geese tested by the haemagglutination inhibition (HI) test. Antiribonucleoprotein antibody was found in 8 of 1 359 sera tested by the agar gel precipitation (AGP) test. An increase in the percentage of reactors was seen each year. This increase was greater in two refuges with nonmigratory flocks. HI antibody was found against the turkey/Wisconsin/66, turkey/Wisconsin/68, turkey/Canada/63, and turkey/Alberta/6962/66, or closely related viruses. No antibody was found against duck/Ukraine/1/63 or human A/Hong Kong/68 virus at a time when the latter was prevalent in human populations, suggesting that Canada geese played no direct role in spreading the virus.Canada geese were experimentally exposed to turkey/Wisconsin/66 and turkey/Wisconsin/68 viruses; mallard ducks were exposed to turkey/Wisconsin/66 virus. HI antibody developed in 75% of the geese and 40% of the ducks but was generally short-lived. Anti-RNP antibody was detected in 15% of the exposed geese but in none of the ducks. Virus was recovered from 3 of 10 adult ducks but not from geese. None of the birds showed signs of disease. PMID:4541003

  10. Anti-influenza M2e antibody

    DOEpatents

    Bradbury, Andrew M.

    2013-04-16

    Humanized recombinant and monoclonal antibodies specific for the ectodomain of the influenza virus M2 ion channel protein are disclosed. The antibodies of the invention have anti-viral activity and may be useful as anti-viral therapeutics and/or prophylactic/vaccine agents for inhibiting influenza virus replication and for treating individuals infected with influenza.

  11. Anti-influenza M2e antibody

    DOEpatents

    Bradbury, Andrew M.

    2011-12-20

    Humanized recombinant and monoclonal antibodies specific for the ectodomain of the influenza virus M2 ion channel protein are disclosed. The antibodies of the invention have anti-viral activity and may be useful as anti-viral therapeutics and/or prophylactic/vaccine agents for inhibiting influenza virus replication and for treating individuals infected with influenza.

  12. 76 FR 24793 - Highly Pathogenic Avian Influenza

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-03

    ... Inspection Service 9 CFR Parts 93, 94, and 95 RIN 0579-AC36 Highly Pathogenic Avian Influenza AGENCY: Animal... products from regions where any subtype of highly pathogenic avian influenza is considered to exist. The... vaccinated for certain types of avian influenza, or that have moved through regions where any subtype...

  13. DIVA vaccination strategies for avian influenza virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Vaccination for both low pathogenic and highly pathogenic avian influenza is commonly used for countries that have been endemic for avian influenza influenza virus, but stamping out policies are common for countries that are normally free of the disease. Stamping out policies of euthanizing infecte...

  14. Swine Influenza Viruses: a North American Perspective

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Influenza is a zoonotic viral disease that represents a health and economic threat to both humans and animals worldwide. Swine influenza was first recognized clinically in pigs in the Midwestern U.S. in 1918, coinciding with the human influenza pandemic known as the Spanish flu. Since that time swin...

  15. Integrating computational modeling and functional assays to decipher the structure-function relationship of influenza virus PB1 protein

    PubMed Central

    Li, Chunfeng; Wu, Aiping; Peng, Yousong; Wang, Jingfeng; Guo, Yang; Chen, Zhigao; Zhang, Hong; Wang, Yongqiang; Dong, Jiuhong; Wang, Lulan; Qin, F. Xiao-Feng; Cheng, Genhong; Deng, Tao; Jiang, Taijiao

    2014-01-01

    The influenza virus PB1 protein is the core subunit of the heterotrimeric polymerase complex (PA, PB1 and PB2) in which PB1 is responsible for catalyzing RNA polymerization and binding to the viral RNA promoter. Among the three subunits, PB1 is the least known subunit so far in terms of its structural information. In this work, by integrating template-based structural modeling approach with all known sequence and functional information about the PB1 protein, we constructed a modeled structure of PB1. Based on this model, we performed mutagenesis analysis for the key residues that constitute the RNA template binding and catalytic (TBC) channel in an RNP reconstitution system. The results correlated well with the model and further identified new residues of PB1 that are critical for RNA synthesis. Moreover, we derived 5 peptides from the sequence of PB1 that form the TBC channel and 4 of them can inhibit the viral RNA polymerase activity. Interestingly, we found that one of them named PB1(491–515) can inhibit influenza virus replication by disrupting viral RNA promoter binding activity of polymerase. Therefore, this study has not only deepened our understanding of structure-function relationship of PB1, but also promoted the development of novel therapeutics against influenza virus. PMID:25424584

  16. Impact of Ancillary Subunits on Ventricular Repolarization

    PubMed Central

    Abbott, Geoffrey W.; Xu, Xianghua; Roepke, Torsten K.

    2007-01-01

    Voltage-gated potassium (Kv) channels generate the outward K+ ion currents that constitute the primary force in ventricular repolarization. Kv channels comprise tetramers of pore-forming α subunits and, in probably the majority of cases in vivo, ancillary or β subunits that help define the properties of the Kv current generated. Ancillary subunits can be broadly categorized as cytoplasmic or transmembrane, and can modify Kv channel trafficking, conductance, gating, ion selectivity, regulation and pharmacology. Because of their often profound effects on Kv channel function, studies of the molecular correlates of ventricular repolarization must take into account ancillary subunits as well as α subunits. Cytoplasmic ancillary subunits include the Kvβ subunits, which regulate a range of Kv channels and may link channel gating to redox potential; and the KChIPs, which appear most often associated with Kv4 subfamily channels that generate the ventricular Ito current. Transmembrane ancillary subunits include the MinK-related proteins (MiRPs) encoded by KCNE genes, which modulate members of most Kv α subunit subfamilies; and the putative 12-transmembrane domain KCR1 protein which modulates hERG. In some cases, such as the ventricular IKs channel complex, it is well-established that the KCNQ1 α subunit must co-assemble with the MinK (KCNE1) single transmembrane domain ancillary subunit for recapitulation of the characteristic, unusually slowly-activating IKs current. In other cases it is not so clear-cut, and in particular the roles of the other MinK-related proteins (MiRPs 1–4) in regulating cardiac Kv channels such as KCNQ1 and hERG in vivo are under debate. MiRP1 alters hERG function and pharmacology, and inherited MiRP1 mutations are associated with inherited and acquired arrhythmias, but controversy exists over the native role of MiRP1 in regulating hERG (and therefore ventricular IKr) in vivo. Some ancillary subunits may exhibit varied expression to shape

  17. An outbreak of the 2009 influenza a (H1N1) virus in a children’s hospital

    PubMed Central

    Bearden, Allison; Friedrich, Thomas C.; Goldberg, Tony L.; Byrne, Barbara; Spiegel, Carol; Schult, Peter; Safdar, Nasia

    2012-01-01

    Please cite this paper as: Bearden et al. (2012) An outbreak of the 2009 influenza a (H1N1) virus in a children’s hospital. Influenza and Other Respiratory Viruses 6(5), 374–379. Context  Preventing nosocomial transmission of influenza is essential to reduce the morbidity and mortality associated with this infection. In October 2009, an outbreak of the 2009 influenza A (H1N1) virus occurred in a hematology ward of a children’s hospital over a 21‐day period and involved two patients and four healthcare workers. Objective  To investigate nosocomial transmission of the 2009 influenza A (H1N1) virus in patients and healthcare workers. Design, setting, and participants  An outbreak investigation was initiated in response to suspected nosocomial transmission of the 2009 influenza A (H1N1) virus during the peak of the 2009 pandemic. Cases were confirmed using a polymerase chain reaction (PCR) test specific for the 2009 H1N1 influenza A virus. Viruses isolated from nasopharyngeal swabs were genetically characterized using Sanger sequencing of uncloned “bulk” PCR products. Main outcome measures  Virus sequencing to investigate nosocomial transmission. Results  Two immunocompromised patients and four healthcare workers were found to be part of a nosocomial outbreak of the 2009 influenza A (H1N1) virus. One immunocompromised patient had a second episode of clinical influenza infection after isolation precautions had been discontinued, resulting in additional exposures. Strain‐specific PCR showed that all cases were caused by infection of the 2009 H1N1 virus. Sequencing of viral genes encoding hemagglutinin and polymerase basic subunit 2 (PB2) revealed that all viruses isolated were genetically identical at these loci, including the two episodes occurring in the same immunocompromised patient. Conclusions  Prompt institution of isolation precautions is essential in preventing nosocomial outbreaks of the 2009 novel influenza A (H1N1) virus. Our data

  18. CHD6, a Cellular Repressor of Influenza Virus Replication, Is Degraded in Human Alveolar Epithelial Cells and Mice Lungs during Infection

    PubMed Central

    Alfonso, Roberto; Rodriguez, Ariel; Rodriguez, Paloma; Lutz, Thomas

    2013-01-01

    The influenza virus polymerase associates to an important number of transcription-related proteins, including the largest subunit of the RNA polymerase II complex (RNAP II). Despite this association, degradation of the RNAP II takes place in the infected cells once viral transcription is completed. We have previously shown that the chromatin remodeler CHD6 protein interacts with the influenza virus polymerase complex, represses viral replication, and relocalizes to inactive chromatin during influenza virus infection. In this paper, we report that CHD6 acts as a negative modulator of the influenza virus polymerase activity and is also subjected to degradation through a process that includes the following characteristics: (i) the cellular proteasome is not implicated, (ii) the sole expression of the three viral polymerase subunits from its cloned cDNAs is sufficient to induce proteolysis, and (iii) degradation is also observed in vivo in lungs of infected mice and correlates with the increase of viral titers in the lungs. Collectively, the data indicate that CHD6 degradation is a general effect exerted by influenza A viruses and suggest that this viral repressor may play an important inhibitory role since degradation and accumulation into inactive chromatin occur during the infection. PMID:23408615

  19. Traditional and New Influenza Vaccines

    PubMed Central

    Wong, Sook-San

    2013-01-01

    SUMMARY The challenges in successful vaccination against influenza using conventional approaches lie in their variable efficacy in different age populations, the antigenic variability of the circulating virus, and the production and manufacturing limitations to ensure safe, timely, and adequate supply of vaccine. The conventional influenza vaccine platform is based on stimulating immunity against the major neutralizing antibody target, hemagglutinin (HA), by virus attenuation or inactivation. Improvements to this conventional system have focused primarily on improving production and immunogenicity. Cell culture, reverse genetics, and baculovirus expression technology allow for safe and scalable production, while adjuvants, dose variation, and alternate routes of delivery aim to improve vaccine immunogenicity. Fundamentally different approaches that are currently under development hope to signal new generations of influenza vaccines. Such approaches target nonvariable regions of antigenic proteins, with the idea of stimulating cross-protective antibodies and thus creating a “universal” influenza vaccine. While such approaches have obvious benefits, there are many hurdles yet to clear. Here, we discuss the process and challenges of the current influenza vaccine platform as well as new approaches that are being investigated based on the same antigenic target and newer technologies based on different antigenic targets. PMID:23824369

  20. Preventing influenza in younger children.

    PubMed

    Esposito, S; Tagliabue, C; Tagliaferri, L; Semino, M; Longo, M R; Principi, N

    2012-10-01

    Influenza is common in infants and children: attack rates vary from 23% to 48% each year during inter-pandemic periods, and are even higher during pandemics. Severe cases occur more frequently in children with underlying chronic diseases; however, epidemiological studies have clearly shown that influenza also causes an excess of medical examinations, drug prescriptions and hospitalizations in otherwise healthy children (particularly those aged <5 years), as well as a considerable number of paediatric deaths. Childhood influenza also has a number of social and economic consequences. However, many European health authorities are still reluctant to include influenza vaccinations in their national vaccination programmes for healthy children because, among other things, there are doubts concerning their real ability to evoke a protective immune response, especially in children in the first years of life. New hope for the solution of these problems has come from the introduction of vaccines containing more antigens and the possibility of intradermal administration. However, further studies are needed to establish whether universal influenza vaccination in the first years of life should be recommended, and with which vaccine. PMID:22862744

  1. 1918 Influenza: A Winnebago County, Wisconsin Perspective

    PubMed Central

    Shors, Teri; McFadden, Susan H.

    2009-01-01

    The population of Winnebago County in 1918 was approximately 62,000 residents. It consisted of towns supporting diverse manufacturers surrounded by farming country. For this study, records were revisited, and 1918 to 1920 influenza survivors were interviewed. A pharmacological investigation encompassing the various influenza treatments used in Wisconsin from 1918 to 1920 was documented. In 1918, over 180 individuals perished from influenza, and over 2000 cases were reported in Winnebago County, Wisconsin. Influenza returned in 1920, which some researchers refer to as the “fourth wave,” claiming nearly 50 lives in Winnebago County, Wisconsin. This study also documents the 1920 influenza wave. PMID:19889943

  2. Variant Influenza Associated with Live Animal Markets, Minnesota.

    PubMed

    Choi, M J; Morin, C A; Scheftel, J; Vetter, S M; Smith, K; Lynfield, R

    2015-08-01

    Variant influenza viruses are swine-origin influenza A viruses that cause illness in humans. Surveillance for variant influenza A viruses, including characterization of exposure settings, is important because of the potential emergence of novel influenza viruses with pandemic potential. In Minnesota, we have documented variant influenza A virus infections associated with swine exposure at live animal markets. PMID:24931441

  3. Expression of Functional Influenza Virus RNA Polymerase in the Methylotrophic Yeast Pichia pastoris

    PubMed Central

    Hwang, Jung-Shan; Yamada, Kazunori; Honda, Ayae; Nakade, Kohji; Ishihama, Akira

    2000-01-01

    Influenza virus RNA polymerase with the subunit composition PB1-PB2-PA is a multifunctional enzyme with the activities of both synthesis and cleavage of RNA and is involved in both transcription and replication of the viral genome. In order to produce large amounts of the functional viral RNA polymerase sufficient for analysis of its structure-function relationships, the cDNAs for RNA segments 1, 2, and 3 of influenza virus A/PR/8, each under independent control of the alcohol oxidase gene promoter, were integrated into the chromosome of the methylotrophic yeast Pichia pastoris. Simultaneous expression of all three P proteins in the yeast P. pastoris was achieved by the addition of methanol. To purify the P protein complexes, a sequence coding for a histidine tag was added to the PB2 protein gene at its N terminus. Starting from the induced P. pastoris cell lysate, we partially purified a 3P complex by Ni2+-agarose affinity column chromatography. The 3P complex showed influenza virus model RNA-directed and ApG-primed RNA synthesis in vitro but was virtually inactive without addition of template or primer. The kinetic properties of model template-directed RNA synthesis and the requirements for template sequence were analyzed using the 3P complex. Furthermore, the 3P complex showed capped RNA-primed RNA synthesis. Thus, we conclude that functional influenza virus RNA polymerase with the catalytic properties of a transcriptase is formed in the methylotrophic yeast P. pastoris. PMID:10756019

  4. Heterologous SH3-p85β inhibits influenza A virus replication

    PubMed Central

    2010-01-01

    Phosphatidylinositol 3-kinase (PI3K)/Akt signalling pathway can support the replication of influenza A virus through binding of viral NS1 protein to the Src homology 3 (SH3) domain of p85β regulatory subunit of PI3K. Here we investigated the effect of heterologously overexpressed SH3 on the replication of different influenza A virus subtypes/strains, and on the phosphorylation of Akt in the virus-infected cells. We found that heterologous SH3 reduced replication of influenza A viruses at varying degrees in a subtype/strain-dependent manner and SH3 overexpression reduced the induction of the phosphorylation of Akt in the cells infected with PR8(H1N1) and ST364(H3N2), but not with ST1233(H1N1), Ph2246(H9N2), and Qa199(H9N2). Our results suggest that interference with the NS1-p85β interaction by heterologous SH3 can be served as a useful antiviral strategy against influenza A virus infection. PMID:20653952

  5. Towards multiscale modeling of influenza infection

    PubMed Central

    Murillo, Lisa N.; Murillo, Michael S.; Perelson, Alan S.

    2013-01-01

    Aided by recent advances in computational power, algorithms, and higher fidelity data, increasingly detailed theoretical models of infection with influenza A virus are being developed. We review single scale models as they describe influenza infection from intracellular to global scales, and, in particular, we consider those models that capture details specific to influenza and can be used to link different scales. We discuss the few multiscale models of influenza infection that have been developed in this emerging field. In addition to discussing modeling approaches, we also survey biological data on influenza infection and transmission that is relevant for constructing influenza infection models. We envision that, in the future, multiscale models that capitalize on technical advances in experimental biology and high performance computing could be used to describe the large spatial scale epidemiology of influenza infection, evolution of the virus, and transmission between hosts more accurately. PMID:23608630

  6. Bacterium-Like Particles for Efficient Immune Stimulation of Existing Vaccines and New Subunit Vaccines in Mucosal Applications

    PubMed Central

    Van Braeckel-Budimir, Natalija; Haijema, Bert Jan; Leenhouts, Kees

    2013-01-01

    The successful development of a mucosal vaccine depends critically on the use of a safe and effective immunostimulant and/or carrier system. This review describes the effectiveness and mode of action of an immunostimulating particle, derived from bacteria, used in mucosal subunit vaccines. The non-living particles, designated bacterium-like particles are based on the food-grade bacterium Lactococcus lactis. The focus of the overview is on the development of intranasal BLP-based vaccines to prevent diseases caused by influenza and respiratory syncytial virus, and includes a selection of Phase I clinical data for the intranasal FluGEM vaccine. PMID:24062748

  7. Cleft Lip Repair: The Hybrid Subunit Method.

    PubMed

    Tollefson, Travis T

    2016-04-01

    The unilateral cleft lip repair is one of the most rewarding and challenging of plastic surgery procedures. Surgeons have introduced a variety of straight line, geometric, and rotation-advancement designs, while in practice the majority of North American surgeons have been using hybrids of the rotation-advancement techniques. The anatomic subunit approach was introduced in 2005 by Fisher and has gained popularity, with early adopters of the design touting its simplicity and effectiveness. The objectives of this article are to summarize the basic tenets of respecting the philtral subunit, accurate measurement and planning, and tips for transitioning to this subunit approach. PMID:27097136

  8. Influenza, Immune System, and Pregnancy

    PubMed Central

    Raj, Renju S.; Bonney, Elizabeth A.

    2014-01-01

    Influenza is a major health problem worldwide. Both seasonal influenza and pandemics take a major toll on the health and economy of our country. The present review focuses on the virology and complex immunology of this RNA virus in general and in relation to pregnancy. The goal is to attempt to explain the increased morbidity and mortality seen in infection during pregnancy. We discuss elements of innate and adaptive immunity as well as placental cellular responses to infection. In addition, we delineate findings in animal models as well as human disease. Increased knowledge of maternal and fetal immunologic responses to influenza is needed. However, enhanced understanding of nonimmune, pregnancy-specific factors influencing direct interaction of the virus with host cells is also important for the development of more effective prevention and treatment options in the future. PMID:24899469

  9. Nuclear dynamics of influenza A virus ribonucleoproteins revealed by live-cell imaging studies

    PubMed Central

    Loucaides, Eva M.; von Kirchbach, Johann C.; Foeglein, Ágnes; Sharps, Jane; Fodor, Ervin; Digard, Paul

    2009-01-01

    The negative sense RNA genome of influenza A virus is transcribed and replicated in the nuclei of infected cells by the viral RNA polymerase. Only four viral polypeptides are required but multiple cellular components are potentially involved. We used fluorescence recovery after photobleaching (FRAP) to characterise the dynamics of GFP-tagged viral ribonucleoprotein (RNP) components in living cells. The nucleoprotein (NP) displayed very slow mobility that significantly increased on formation of transcriptionally active RNPs. Conversely, single or dimeric polymerase subunits showed fast nuclear dynamics that decreased upon formation of heterotrimers, suggesting increased interaction of the full polymerase complex with a relatively immobile cellular component(s). Treatment with inhibitors of cellular transcription indicated that in part, this reflected an interaction with cellular RNA polymerase II. Analysis of mutated influenza virus polymerase complexes further suggested that this was through an interaction between PB2 and RNA Pol II separate from PB2 cap-binding activity. PMID:19744689

  10. Nuclear dynamics of influenza A virus ribonucleoproteins revealed by live-cell imaging studies

    SciTech Connect

    Loucaides, Eva M.; Kirchbach, Johann C. von; Foeglein, Agnes; Sharps, Jane; Fodor, Ervin; Digard, Paul

    2009-11-10

    The negative sense RNA genome of influenza A virus is transcribed and replicated in the nuclei of infected cells by the viral RNA polymerase. Only four viral polypeptides are required but multiple cellular components are potentially involved. We used fluorescence recovery after photobleaching (FRAP) to characterise the dynamics of GFP-tagged viral ribonucleoprotein (RNP) components in living cells. The nucleoprotein (NP) displayed very slow mobility that significantly increased on formation of transcriptionally active RNPs. Conversely, single or dimeric polymerase subunits showed fast nuclear dynamics that decreased upon formation of heterotrimers, suggesting increased interaction of the full polymerase complex with a relatively immobile cellular component(s). Treatment with inhibitors of cellular transcription indicated that in part, this reflected an interaction with cellular RNA polymerase II. Analysis of mutated influenza virus polymerase complexes further suggested that this was through an interaction between PB2 and RNA Pol II separate from PB2 cap-binding activity.

  11. Influenza A virus recycling revisited.

    PubMed Central

    Dowdle, W. R.

    1999-01-01

    Current textbooks link influenza pandemics to influenza A virus subtypes H2 (1889-91), H3 (1990), H1 (1918-20), H2 (1957-58) and H3 (1968), a pattern suggesting subtype recycling in humans. Since H1 reappeared in 1977, whatever its origin, some workers feel that H2 is the next pandemic candidate. This report reviews the publications on which the concept of influenza A virus subtype recycling is based and concludes that the data are inconsistent with the purported sequence of events. The three influenza pandemics prior to 1957-58 were linked with subtypes through retrospective studies of sera from the elderly, or through seroarchaeology. The pandemic seroarchaeological model for subtype H1 has been validated by the recent recovery of swine virus RNA fragments from persons who died from influenza in 1918. Application of the model to pre-existing H3 antibody among the elderly links the H3 subtype to the pandemic of 1889-91, not that of 1900 as popularly quoted. Application of the model to pre-existing H2 antibody among the elderly fails to confirm that this subtype caused a pandemic in the late 1800's, a finding which is consistent with age-related excess mortality patterns during the pandemics of 1957 (H2) and 1968 (H3). H2 variants should be included in pandemic planning for a number of reasons, but not because of evidence of recycling. It is not known when the next pandemic will occur or which of the 15 (or more) haemagglutinin subtypes will be involved. Effective global surveillance remains the key to influenza preparedness. PMID:10593030

  12. A novel small-molecule inhibitor of influenza A virus acts by suppressing PA endonuclease activity of the viral polymerase

    PubMed Central

    Yuan, Shuofeng; Chu, Hin; Singh, Kailash; Zhao, Hanjun; Zhang, Ke; Kao, Richard Y. T.; Chow, Billy K. C.; Zhou, Jie; Zheng, Bo-Jian

    2016-01-01

    The RNA-dependent RNA polymerase of influenza A virus comprises conserved and independently-folded subdomains with defined functionalities. The N-terminal domain of the PA subunit (PAN) harbors the endonuclease function so that it can serve as a desired target for drug discovery. To identify a class of anti-influenza inhibitors that impedes PAN endonuclease activity, a screening approach that integrated the fluorescence resonance energy transfer based endonuclease inhibitory assay with the DNA gel-based endonuclease inhibitory assay was conducted, followed by the evaluation of antiviral efficacies and potential cytotoxicity of the primary hits in vitro and in vivo. A small-molecule compound ANA-0 was identified as a potent inhibitor against the replication of multiple subtypes of influenza A virus, including H1N1, H3N2, H5N1, H7N7, H7N9 and H9N2, in cell cultures. Combinational treatment of zanamivir and ANA-0 exerted synergistic anti-influenza effect in vitro. Intranasal administration of ANA-0 protected mice from lethal challenge and reduced lung viral loads in H1N1 virus infected BALB/c mice. In summary, ANA-0 shows potential to be developed to novel anti-influenza agents. PMID:26956222

  13. A simple Pichia pastoris fermentation and downstream processing strategy for making recombinant pandemic Swine Origin Influenza a virus Hemagglutinin protein.

    PubMed

    Athmaram, T N; Singh, Anil Kumar; Saraswat, Shweta; Srivastava, Saurabh; Misra, Princi; Kameswara Rao, M; Gopalan, N; Rao, P V L

    2013-02-01

    The present Influenza vaccine manufacturing process has posed a clear impediment to initiation of rapid mass vaccination against spreading pandemic influenza. New vaccine strategies are therefore needed that can accelerate the vaccine production. Pichia offers several advantages for rapid and economical bulk production of recombinant proteins and, hence, can be attractive alternative for producing an effective influenza HA based subunit vaccine. The recombinant Pichia harboring the transgene was subjected to fed-batch fermentation at 10 L scale. A simple fermentation and downstream processing strategy is developed for high-yield secretory expression of the recombinant Hemagglutinin protein of pandemic Swine Origin Influenza A virus using Pichia pastoris via fed-batch fermentation. Expression and purification were optimized and the expressed recombinant Hemagglutinin protein was verified by sodium dodecyl sulfate polyacrylamide gel electrophoresis, Western blot and MALDI-TOF analysis. In this paper, we describe a fed-batch fermentation protocol for the secreted production of Swine Influenza A Hemagglutinin protein in the P. pastoris GS115 strain. We have shown that there is a clear relationship between product yield and specific growth rate. The fed-batch fermentation and downstream processing methods optimized in the present study have immense practical application for high-level production of the recombinant H1N1 HA protein in a cost effective way using P. pastoris. PMID:23247902

  14. Influenza vaccination of healthcare personnel.

    PubMed

    Wicker, Sabine; Marckmann, Georg

    2014-01-01

    The thought is terrifying--you are admitted to the hospital and you die of a nosocomial infection. What sounds like a horror scenario, happens every day in hospitals all over the world. Nosocomial influenza is associated with considerable morbidity and mortality among patients with underlying diseases (especially immunocompromised patients), the elderly, and neonates. Although vaccination of healthcare personnel (HCP) is the main measure for preventing nosocomial influenza and is consistently recommended by public-health authorities, vaccine uptake among HCP remains low. (1.) PMID:25483507

  15. Influenza vaccination of healthcare personnel

    PubMed Central

    Wicker, Sabine; Marckmann, Georg

    2014-01-01

    The thought is terrifying—you are admitted to the hospital and you die of a nosocomial infection. What sounds like a horror scenario, happens every day in hospitals all over the world. Nosocomial influenza is associated with considerable morbidity and mortality among patients with underlying diseases (especially immunocompromised patients), the elderly, and neonates. Although vaccination of healthcare personnel (HCP) is the main measure for preventing nosocomial influenza and is consistently recommended by public-health authorities, vaccine uptake among HCP remains low.1 PMID:25483507

  16. Equine influenza serological methods.

    PubMed

    Chambers, Thomas M; Reedy, Stephanie E

    2014-01-01

    Serologic tests for equine influenza virus (EIV) antibodies are used for many purposes, including retrospective diagnosis, subtyping of virus isolates, antigenic comparison of different virus strains, and measurement of immune responses to EIV vaccines. The hemagglutination-inhibition (HI), single radial hemolysis (SRH), and serum micro-neutralization tests are the most widely used for these purposes and are described here. The presence of inhibitors of hemagglutination in equine serum complicates interpretation of HI assay results, and there are alternative protocols (receptor-destroying enzyme, periodate, trypsin-periodate) for their removal. With the EIV H3N8 strains in particular, equine antibody titers may be magnified by pretreating the HI test antigen with Tween-80 and ether. The SRH assay offers stronger correlations between serum antibody titers and protection from disease. Other tests are sometimes used for specialized purposes such as the neuraminidase-inhibition assay for subtyping, or ELISA for measuring different specific antibody isotypes, and are not described here. PMID:24899450

  17. Epidemiological and virological characteristics of influenza B: results of the Global Influenza B Study

    PubMed Central

    Caini, Saverio; Huang, Q Sue; Ciblak, Meral A; Kusznierz, Gabriela; Owen, Rhonda; Wangchuk, Sonam; Henriques, Cláudio M P; Njouom, Richard; Fasce, Rodrigo A; Yu, Hongjie; Feng, Luzhao; Zambon, Maria; Clara, Alexey W; Kosasih, Herman; Puzelli, Simona; Kadjo, Herve A; Emukule, Gideon; Heraud, Jean-Michel; Ang, Li Wei; Venter, Marietjie; Mironenko, Alla; Brammer, Lynnette; Mai, Le Thi Quynh; Schellevis, François; Plotkin, Stanley; Paget, John

    2015-01-01

    Introduction Literature on influenza focuses on influenza A, despite influenza B having a large public health impact. The Global Influenza B Study aims to collect information on global epidemiology and burden of disease of influenza B since 2000. Methods Twenty-six countries in the Southern (n = 5) and Northern (n = 7) hemispheres and intertropical belt (n = 14) provided virological and epidemiological data. We calculated the proportion of influenza cases due to type B and Victoria and Yamagata lineages in each country and season; tested the correlation between proportion of influenza B and maximum weekly influenza-like illness (ILI) rate during the same season; determined the frequency of vaccine mismatches; and described the age distribution of cases by virus type. Results The database included 935 673 influenza cases (2000–2013). Overall median proportion of influenza B was 22·6%, with no statistically significant differences across seasons. During seasons where influenza B was dominant or co-circulated (>20% of total detections), Victoria and Yamagata lineages predominated during 64% and 36% of seasons, respectively, and a vaccine mismatch was observed in ≈25% of seasons. Proportion of influenza B was inversely correlated with maximum ILI rate in the same season in the Northern and (with borderline significance) Southern hemispheres. Patients infected with influenza B were usually younger (5–17 years) than patients infected with influenza A. Conclusion Influenza B is a common disease with some epidemiological differences from influenza A. This should be considered when optimizing control/prevention strategies in different regions and reducing the global burden of disease due to influenza. PMID:26256290

  18. Detection of influenza C virus but not influenza D virus in Scottish respiratory samples

    PubMed Central

    Smith, Donald B.; Gaunt, Eleanor R.; Digard, Paul; Templeton, Kate; Simmonds, Peter

    2016-01-01

    Background A newly proposed genus of influenza virus (influenza D) is associated with respiratory disease in pigs and cattle. The novel virus is most closely related to human influenza C virus and can infect ferrets but infection has not been reported in humans. Objectives To ascertain if influenza D virus can be detected retrospectively in patient respiratory samples. Study design 3300 human respiratory samples from Edinburgh, Scotland, covering the period 2006–2008, were screened in pools of 10 by RT-PCR using primers capable of detecting both influenza C and D viruses. Results Influenza D was not detected in any sample. Influenza C was present in 6 samples (0.2%), compared with frequencies of 3.3% and 0.9% for influenza A and B viruses from RT-PCR testing of respiratory samples over the same period. Influenza C virus was detected in samples from individuals <2 years or >45 years old, with cases occurring throughout the year. Phylogenetic analysis of nearly complete sequences of all seven segments revealed the presence of multiple, reassortant lineages. Conclusion We were unable to detect viruses related to influenza D virus in human respiratory samples. Influenza C virus was less prevalent than influenza A and B viruses, was associated with mild disease in the young (<2 years) and old (>45 years) and comprised multiple, reassortant lineages. Inclusion of influenza C virus as part of a diagnostic testing panel for respiratory infections would be of limited additional value. PMID:26655269

  19. Influenza (Flu) vaccine (Live, Intranasal): What you need to know

    MedlinePlus

    ... is taken in its entirety from the CDC Influenza Live, Intranasal Flu Vaccine Information Statement (VIS): www.cdc.gov/vaccines/ ... flulive.html . CDC review information for Live, Intranasal Influenza VIS: Vaccine Information Statement Influenza Page last reviewed: ...

  20. Antibiotic Prescription Practices Among Children with Influenza.

    PubMed

    Nitsch-Osuch, A; Gyrczuk, E; Wardyn, A; Życinska, K; Brydak, L

    2016-01-01

    The important factor in the development of resistance to antibiotics is their overuse, especially for viral respiratory infections. The aim of the study was to find out the frequency of the antibiotic therapy administrated to children with influenza. A total of 114 children younger than 59 months seeking care for the acute respiratory tract infection was enrolled into the study. The patients had influenza-like symptoms: fever > 38 °C, cough, and sore throat of less than 4 days duration. Nasal and pharyngeal swabs were tested for influenza A and B virus with a real-time PCR. Thirty six cases of influenza were diagnosed: 34 of influenza A (H3N2) and 2 of influenza B. The rate of influenza infection was 32 % in the study group. The antibiotic therapy was ordered for 58 % patients with influenza. Antibiotics were given less frequently in the outpatient setting (33 %) compared with the hospitalized patients (93 %) (p < 0.05). The most often administrated antibiotics were amoxicillin with clavulanic acid, cefuroxime, and amoxicillin. None of the patients received oseltamivir. Antibiotics were overused, while antivirals were underused among children with influenza. To improve health care quality, more efforts in the diagnosis of influenza and the appropriate use of antimicrobials and antivirals are required. PMID:26801146

  1. Virus-Vectored Influenza Virus Vaccines

    PubMed Central

    Tripp, Ralph A.; Tompkins, S. Mark

    2014-01-01

    Despite the availability of an inactivated vaccine that has been licensed for >50 years, the influenza virus continues to cause morbidity and mortality worldwide. Constant evolution of circulating influenza virus strains and the emergence of new strains diminishes the effectiveness of annual vaccines that rely on a match with circulating influenza strains. Thus, there is a continued need for new, efficacious vaccines conferring cross-clade protection to avoid the need for biannual reformulation of seasonal influenza vaccines. Recombinant virus-vectored vaccines are an appealing alternative to classical inactivated vaccines because virus vectors enable native expression of influenza antigens, even from virulent influenza viruses, while expressed in the context of the vector that can improve immunogenicity. In addition, a vectored vaccine often enables delivery of the vaccine to sites of inductive immunity such as the respiratory tract enabling protection from influenza virus infection. Moreover, the ability to readily manipulate virus vectors to produce novel influenza vaccines may provide the quickest path toward a universal vaccine protecting against all influenza viruses. This review will discuss experimental virus-vectored vaccines for use in humans, comparing them to licensed vaccines and the hurdles faced for licensure of these next-generation influenza virus vaccines. PMID:25105278

  2. Liver involvement during influenza infection: perspective on the 2009 influenza pandemic

    PubMed Central

    Papic, Neven; Pangercic, Ana; Vargovic, Martina; Barsic, Bruno; Vince, Adriana; Kuzman, Ilija

    2011-01-01

    Please cite this paper as: Papic et al. (2011) Liver involvement during influenza infection: perspective on the 2009 influenza pandemic. Influenza and Other Respiratory Viruses 6(3), e2–e5. Elevation of liver transaminase levels is a frequent observation during systemic infections. The aim of our study was to investigate liver damage during pandemic 2009 influenza A/H1N1 infection in comparison with seasonal influenza. Serum levels of aspartate aminotransferase, alanine aminotransferase, and gamma‐glutamyl transpeptidase (GGT) were significantly higher in patients with pandemic influenza compared to seasonal influenza, which was strongly correlated with hypoxia. Moreover, a positive correlation between C‐reactive protein and serum GGT, alkaline phosphatase, and lactate dehydrogenase was noticed. Our findings support the hypothesis that the pandemic 2009 influenza A/H1N1 is an illness with a significant immune response to infection leading to hepatocellular injury. PMID:21951624

  3. Expression and Characterization of Recombinant, Tetrameric and Enzymatically Active Influenza Neuraminidase for the Setup of an Enzyme-Linked Lectin-Based Assay

    PubMed Central

    Prevato, Marua; Ferlenghi, Ilaria; Bonci, Alessandra; Uematsu, Yasushi; Anselmi, Giulia; Giusti, Fabiola; Bertholet, Sylvie; Legay, Francois; Telford, John Laird; Settembre, Ethan C.; Maione, Domenico; Cozzi, Roberta

    2015-01-01

    Developing a universal influenza vaccine that induces broad spectrum and longer-term immunity has become an important potentially achievable target in influenza vaccine research and development. Hemagglutinin (HA) and neuraminidase (NA) are the two major influenza virus antigens. Although antibody responses against influenza virus are mainly directed toward HA, NA is reported to be more genetically stable; hence NA-based vaccines have the potential to be effective for longer time periods. NA-specific immunity has been shown to limit the spread of influenza virus, thus reducing disease symptoms and providing cross-protection against heterosubtypic viruses in mouse challenge experiments. The production of large quantities of highly pure and stable NA could be beneficial for the development of new antivirals, subunit-based vaccines, and novel diagnostic tools. In this study, recombinant NA (rNA) was produced in mammalian cells at high levels from both swine A/California/07/2009 (H1N1) and avian A/turkey/Turkey/01/2005 (H5N1) influenza viruses. Biochemical, structural, and immunological characterizations revealed that the soluble rNAs produced are tetrameric, enzymatically active and immunogenic, and finally they represent good alternatives to conventionally used sources of NA in the Enzyme-Linked Lectin Assay (ELLA). PMID:26280677

  4. Dynamic changes during acid-induced activation of influenza hemagglutinin

    PubMed Central

    Garcia, Natalie K.; Guttman, Miklos; Ebner, Jamie L.; Lee, Kelly K.

    2015-01-01

    SUMMARY Influenza hemagglutinin (HA) mediates virus attachment to host cells and fusion of the viral and endosomal membranes during entry. While high-resolution structures are available for the pre-fusion HA ectodomain and the post-fusion HA2 subunit, the sequence of conformational changes during HA activation has eluded structural characterization. Here we apply hydrogen-deuterium exchange with mass spectrometry to examine changes in structural dynamics of the HA ectodomain at various stages of activation, as well as to compare the soluble ectodomain with intact HA on virions. At pH conditions approaching activation (pH 6.0–5.5) HA exhibits increased dynamics at the fusion peptide and neighboring regions, while the interface between receptor-binding subunits (HA1) becomes stabilized. In contrast to many activation models, these data suggest that HA responds to endosomal acidification by releasing the fusion peptide prior to HA1 uncaging and the spring-loaded refolding of HA2. This staged process may facilitate efficient HA-mediated fusion. PMID:25773144

  5. New vaccines against influenza virus

    PubMed Central

    Lee, Young-Tae; Kim, Ki-Hye; Ko, Eun-Ju; Lee, Yu-Na; Kim, Min-Chul; Kwon, Young-Man; Tang, Yinghua; Cho, Min-Kyoung; Lee, Youn-Jeong

    2014-01-01

    Vaccination is one of the most effective and cost-benefit interventions that prevent the mortality and reduce morbidity from infectious pathogens. However, the licensed influenza vaccine induces strain-specific immunity and must be updated annually based on predicted strains that will circulate in the upcoming season. Influenza virus still causes significant health problems worldwide due to the low vaccine efficacy from unexpected outbreaks of next epidemic strains or the emergence of pandemic viruses. Current influenza vaccines are based on immunity to the hemagglutinin antigen that is highly variable among different influenza viruses circulating in humans and animals. Several scientific advances have been endeavored to develop universal vaccines that will induce broad protection. Universal vaccines have been focused on regions of viral proteins that are highly conserved across different virus subtypes. The strategies of universal vaccines include the matrix 2 protein, the hemagglutinin HA2 stalk domain, and T cell-based multivalent antigens. Supplemented and/or adjuvanted vaccination in combination with universal target antigenic vaccines would have much promise. This review summarizes encouraging scientific advances in the field with a focus on novel vaccine designs. PMID:24427759

  6. Avian influenza virus RNA extraction

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The efficient extraction and purification of viral RNA is critical for down-stream molecular applications whether it is the sensitive and specific detection of virus in clinical samples, virus gene cloning and expression, or quantification of avian influenza (AI) virus by molecular methods from expe...

  7. Immunosuppression During Influenza Virus Infection

    PubMed Central

    Kantzler, G. B.; Lauteria, S. F.; Cusumano, C. L.; Lee, J. D.; Ganguly, R.; Waldman, R. H.

    1974-01-01

    The effects of a live attenuated influenza vaccine and subsequent challenge with virulent influenza virus on the delayed hypersensitivity skin test, and the in vitro response of lymphocytes were evaluated. Volunteers were skin tested before and after administration of vaccine or placebo and challenge with PPD (a purified protein derivative of Mycobacterium tuberculosis), candida, mumps, and trichophytin, and their lymphocytes were tested for [3H]thymidine uptake in response to phytohemagglutin. Of eight volunteers who showed evidence of viral replication after administration of the attenuated vaccine, four had a significant diminution in their skin test response, whereas 8 of 13 volunteers infected with virulent influenza virus showed a diminution. Of the 21 volunteers who were infected with either attenuated or virulent influenza virus, 12 showed suppression of their phytohemagglutin response. None of the volunteers who were given placebo vaccine, or who showed no evidence for viral replication after immunization or challenge, had a suppression of their skin test or phytohemagglutin responses. Although most of the infected volunteers demonstrated suppression of their T-cell function, there was no evidence of a similar suppression of B-cell function. PMID:16558116

  8. Avian Influenza: Our current understanding

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Avian influenza virus (AIV) has become one of the most important diseases of the poultry industry around the world. The virus has a broad host range in birds and mammals, although the natural reservoir is considered to be in wild birds where it typically causes an asymptomatic to mild infection. T...

  9. Swine Influenza Virus: Emerging Understandings

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Introduction: In March-April 2009, a novel pandemic H1N1 emerged in the human population in North America [1]. The gene constellation of the emerging virus was demonstrated to be a combination of genes from swine influenza A viruses (SIV) of North American and Eurasian lineages that had never before...

  10. Avian influenza vaccination and control

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Avian influenza (AI) remains an economic threat to commercial poultry throughout the world by negatively impacting animal health and trade. Vaccination with high quality efficacious vaccines that are properly delivered can contribute to the control of avian AI outbreaks when used as part of a compr...

  11. Influenza vaccines for avian species

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Beginning in Southeast Asia, in 2003, a multi-national epizootic outbreak of H5N1 highly pathogenic avian influenza (HPAI) was identified in commercial poultry and wild bird species. This lineage, originally identified in Southern China in 1996 and then Hong Kong in 1997, caused severe morbidity an...

  12. Epitope specificity of anti‐HA2 antibodies induced in humans during influenza infection

    PubMed Central

    Staneková, Zuzana; Mucha, Vojtech; Sládková, Tatiana; Blaškovičová, Hana; Kostolanský, František; Varečková, Eva

    2012-01-01

    Please cite this paper as: Stanekováet al. (2012) Epitope specificity of anti‐HA2 antibodies induced in humans during influenza infection. Influenza and Other Respiratory Viruses 6(6), 389–395. Background  The conserved, fusion‐active HA2 glycopolypeptide (HA2) subunit of influenza A hemagglutinin comprises four distinct antigenic sites. Monoclonal antibodies (MAbs) recognizing three of these sites are broadly cross‐reactive and protective. Objectives  This study aimed to establish whether antibodies specific to these three antigenic sites were elicited during a natural influenza infection or by vaccination of humans. Methods  Forty‐five paired acute and convalescent sera from individuals with a confirmed influenza A (subtype H3) infection were examined for the presence of HA2‐specific antibodies. The fraction of antibodies specific to three particular antigenic sites (designated IIF4, FC12, and CF2 here) was investigated using competitive enzyme immunoassay. Results  Increased levels of antibodies specific to an ectodomain of HA2 (EHA2: N‐terminal residues 23–185 of HA2) were detected in 73% of tested convalescent sera (33/45), while an increased level of antibodies specific to the HA2 fusion peptide (N‐terminal residues 1–38) was induced in just 15/45 individuals (33%). Competitive assays confirmed that antibodies specific to the IIF4 epitope (within HA2 residues 125–175) prevailed in 86% (13/15) over those specific to the other two epitopes during infection. However, only a negligible increase in HA2‐specific antibodies was detectable following vaccination with a current subunit vaccine. Conclusions  We observed that the antigenic site localized within N‐terminal HA2 residues 125–175 was more immunogenic than that within residues 1–38 (HA2 fusion protein), although both are weak natural immunogens. We suggest that new anti‐influenza vaccines should include HA2 (or specific epitopes localized within this

  13. Effectiveness of seasonal influenza vaccination during pregnancy in preventing influenza infection in infants, England, 2013/14.

    PubMed

    Dabrera, G; Zhao, H; Andrews, N; Begum, F; Green, Hk; Ellis, J; Elias, K; Donati, M; Zambon, M; Pebody, R

    2014-01-01

    In this study we used the screening method to estimate the effectiveness of seasonal influenza vaccination during pregnancy in preventing influenza virus infection and influenza-related hospitalisation in infants under six months, in England in the 2013/14 season. Seasonal influenza vaccination in pregnancy was 71% (95% CI: 24–89%) effective in preventing infant influenza virus infection and 64% (95% CI: 6–86%) effective in preventing infant influenza hospitalisation, and should be recommended in pregnancy. PMID:25411687

  14. Evolution and ecology of influenza A viruses.

    PubMed Central

    Webster, R G; Bean, W J; Gorman, O T; Chambers, T M; Kawaoka, Y

    1992-01-01

    In this review we examine the hypothesis that aquatic birds are the primordial source of all influenza viruses in other species and study the ecological features that permit the perpetuation of influenza viruses in aquatic avian species. Phylogenetic analysis of the nucleotide sequence of influenza A virus RNA segments coding for the spike proteins (HA, NA, and M2) and the internal proteins (PB2, PB1, PA, NP, M, and NS) from a wide range of hosts, geographical regions, and influenza A virus subtypes support the following conclusions. (i) Two partly overlapping reservoirs of influenza A viruses exist in migrating waterfowl and shorebirds throughout the world. These species harbor influenza viruses of all the known HA and NA subtypes. (ii) Influenza viruses have evolved into a number of host-specific lineages that are exemplified by the NP gene and include equine Prague/56, recent equine strains, classical swine and human strains, H13 gull strains, and all other avian strains. Other genes show similar patterns, but with extensive evidence of genetic reassortment. Geographical as well as host-specific lineages are evident. (iii) All of the influenza A viruses of mammalian sources originated from the avian gene pool, and it is possible that influenza B viruses also arose from the same source. (iv) The different virus lineages are predominantly host specific, but there are periodic exchanges of influenza virus genes or whole viruses between species, giving rise to pandemics of disease in humans, lower animals, and birds. (v) The influenza viruses currently circulating in humans and pigs in North America originated by transmission of all genes from the avian reservoir prior to the 1918 Spanish influenza pandemic; some of the genes have subsequently been replaced by others from the influenza gene pool in birds. (vi) The influenza virus gene pool in aquatic birds of the world is probably perpetuated by low-level transmission within that species throughout the year. (vii

  15. The emergence of influenza A H7N9 in human beings 16 years after influenza A H5N1: a tale of two cities.

    PubMed

    To, Kelvin K W; Chan, Jasper F W; Chen, Honglin; Li, Lanjuan; Yuen, Kwok-Yung

    2013-09-01

    Infection with either influenza A H5N1 virus in 1997 or avian influenza A H7N9 virus in 2013 caused severe pneumonia that did not respond to typical or atypical antimicrobial treatment, and resulted in high mortality. Both viruses are reassortants with internal genes derived from avian influenza A H9N2 viruses that circulate in Asian poultry. Both viruses have genetic markers of mammalian adaptation in their haemagglutinin and polymerase PB2 subunits, which enhanced binding to human-type receptors and improved replication in mammals, respectively. Hong Kong (affected by H5N1 in 1997) and Shanghai (affected by H7N9 in 2013) are two rapidly flourishing cosmopolitan megacities that were increasing in human population and poultry consumption before the outbreaks. Both cities are located along the avian migratory route at the Pearl River delta and Yangtze River delta. Whether the widespread use of the H5N1 vaccine in east Asia-with suboptimum biosecurity measures in live poultry markets and farms-predisposed to the emergence of H7N9 or other virus subtypes needs further investigation. Why H7N9 seems to be more readily transmitted from poultry to people than H5N1 is still unclear. PMID:23969217

  16. Ambient Influenza and Avian Influenza Virus during Dust Storm Days and Background Days

    PubMed Central

    Chen, Pei-Shih; Tsai, Feng Ta; Lin, Chien Kun; Yang, Chun-Yuh; Chan, Chang-Chuan; Young, Chea-Yuan; Lee, Chien-Hung

    2010-01-01

    Background The spread of influenza and highly pathogenic avian influenza (H5N1) presents a significant threat to human health. Avian influenza outbreaks in downwind areas of Asian dust storms (ADS) suggest that viruses might be transported by dust storms. Objectives We developed a technique to measure ambient influenza and avian influenza viruses. We then used this technique to measure concentrations of these viruses on ADS days and background days, and to assess the relationships between ambient influenza and avian influenza viruses, and air pollutants. Methods A high-volume air sampler was used in parallel with a filter cassette to evaluate spiked samples and unspiked samples. Then, air samples were monitored during ADS seasons using a filter cassette coupled with a real-time quantitative polymerase chain reaction (qPCR) assay. Air samples were monitored during ADS season (1 January to 31 May 2006). Results We successfully quantified ambient influenza virus using the filtration/real-time qPCR method during ADS days and background days. To our knowledge, this is the first report describing the concentration of influenza virus in ambient air. In both the spiked and unspiked samples, the concentration of influenza virus sampled using the filter cassette was higher than that using the high-volume sampler. The concentration of ambient influenza A virus was significantly higher during the ADS days than during the background days. Conclusions Our data imply the possibility of long-range transport of influenza virus. PMID:20435545

  17. Influenza vaccination coverage and factors affecting adherence to influenza vaccination among patients with diabetes in Taiwan

    PubMed Central

    Yu, Mei-Ching; Chou, Yuan-Lin; Lee, Pei-Lun; Yang, Yi-Ching; Chen, Kow-Tong

    2014-01-01

    The purpose of this study was to investigate influenza vaccination coverage and the factors influencing acceptance of influenza vaccination among patients with diabetes in Taiwan using the Health Belief Model (HBM). From January 1 to February 28, 2012, 700 patients with diabetes who visited National Cheng Kung University Hospital were invited to participate in the study. A total of 691 (99%) patients with diabetes were enrolled in the study. The mean age of the subjects was 64.7 years (SD = 10.7). The percentages of patients with diabetes who received seasonal influenza vaccination were 31%, 33%, and 35% in 2009–2010, 2010–2011, and 2011–2012, respectively. Multiple regression analyses revealed that patients with diabetes who were female, were older, had comorbidities, had a more positive perception of the benefits of the influenza vaccine and had lower perceived barriers to influenza vaccination were more likely to receive the influenza vaccine in 2011–2012 (adjusted R2 = 0.47; Chi-square = 276.50; P < 0.001). Patients with diabetes perceived the risk of swine influenza to be similar to that of seasonal influenza. Consequently, in the absence of an increase in the perceived risk of influenza, a low level of actual vaccination against seasonal influenza is forecasted. Strategies to improve the uptake of influenza vaccination include interventions that highlight the risk posed by pandemic influenza while simultaneously offering tactics to ameliorate this risk. PMID:24503629

  18. Avian influenza: the Canadian experience.

    PubMed

    Pasick, J; Berhane, Y; Hooper-McGrevy, K

    2009-04-01

    Reports of sporadic avian influenza outbreaks involving domestic poultry date back to the 1960s. With the exception of A/turkey/Ontario/7732/1966 (H5N9), which was isolated from a turkey breeding establishment, all viruses characterised prior to 2004 fit the criteria of low pathogenic avian influenza (LPAI). Only in retrospect was A/turkey/Ontario/7732/1966 shown to meet the criteria of a highly pathogenic avian influenza (HPAI). In 2004, Canada reported its first case of HPAI to the World Organisation for Animal Health (OIE). The outbreak, which began in a broiler breeder farm in the Fraser Valley of British Columbia, involved an H7N3 LPAI virus which underwent a sudden virulence shift to HPAI. More than 17 million birds were culled and CAN$380 million in gross economic costs incurred before the outbreak was eventually brought under control. In its aftermath a number of changes were implemented to mitigate the impact of any future HPAI outbreaks. These changes involved various aspects of avian influenza detection and control, including self-quarantine, biosecurity, surveillance, and laboratory testing. In 2005, a national surveillance programme for influenza A viruses in wild birds was initiated. Results of this survey provided evidence for wild birds as the likely source of an H5N2 LPAI outbreak that occurred in domestic ducks in the Fraser Valley in the autumn of 2005. Wild birds were once again implicated in an H7N3 HPAI outbreak involving a broiler breeder operation in Saskatchewan in 2007. Fortunately, both of these outbreaks were limited in extent, a consequence of some of the changes implemented in response to the 2004 British Columbia outbreak. PMID:19618638

  19. Influenza A virus hemagglutinin protein subunit vaccine elicits vaccine-associated enhanced respiratory disease

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Vaccine-associated enhanced respiratory disease (VAERD) can occur when pigs are challenged with heterologous virus in the presence of non-neutralizing but cross-reactive antibodies elicited by whole inactivated virus (WIV) vaccine. The aim of this study was to compare the effects of heterologous del...

  20. Methods for molecular surveillance of influenza

    PubMed Central

    Wang, Ruixue; Taubenberger, Jeffery K

    2010-01-01

    Molecular-based techniques for detecting influenza viruses have become an integral component of human and animal surveillance programs in the last two decades. The recent pandemic of the swine-origin influenza A virus (H1N1) and the continuing circulation of highly pathogenic avian influenza A virus (H5N1) further stress the need for rapid and accurate identification and subtyping of influenza viruses for surveillance, outbreak management, diagnosis and treatment. There has been remarkable progress on the detection and molecular characterization of influenza virus infections in clinical, mammalian, domestic poultry and wild bird samples in recent years. The application of these techniques, including reverse transcriptase-PCR, real-time PCR, microarrays and other nucleic acid sequencing-based amplifications, have greatly enhanced the capability for surveillance and characterization of influenza viruses. PMID:20455681

  1. Improved Global Capacity for Influenza Surveillance.

    PubMed

    Polansky, Lauren S; Outin-Blenman, Sajata; Moen, Ann C

    2016-06-01

    During 2004-2009, the Centers for Disease Control and Prevention (CDC) partnered with 39 national governments to strengthen global influenza surveillance. Using World Health Organization data and program evaluation indicators collected by CDC in 2013, we retrospectively evaluated progress made 4-9 years after the start of influenza surveillance capacity strengthening in the countries. Our results showed substantial increases in laboratory and sentinel surveillance capacities, which are essential for knowing which influenza strains circulate globally, detecting emergence of novel influenza, identifying viruses for vaccine selection, and determining the epidemiology of respiratory illness. Twenty-eight of 35 countries responding to a 2013 questionnaire indicated that they have leveraged routine influenza surveillance platforms to detect other pathogens. This additional surveillance illustrates increased health-system strengthening. Furthermore, 34 countries reported an increased ability to use data in decision making; data-driven decisions are critical for improving local prevention and control of influenza around the world. PMID:27192395

  2. Improved Global Capacity for Influenza Surveillance

    PubMed Central

    Outin-Blenman, Sajata; Moen, Ann C.

    2016-01-01

    During 2004–2009, the Centers for Disease Control and Prevention (CDC) partnered with 39 national governments to strengthen global influenza surveillance. Using World Health Organization data and program evaluation indicators collected by CDC in 2013, we retrospectively evaluated progress made 4–9 years after the start of influenza surveillance capacity strengthening in the countries. Our results showed substantial increases in laboratory and sentinel surveillance capacities, which are essential for knowing which influenza strains circulate globally, detecting emergence of novel influenza, identifying viruses for vaccine selection, and determining the epidemiology of respiratory illness. Twenty-eight of 35 countries responding to a 2013 questionnaire indicated that they have leveraged routine influenza surveillance platforms to detect other pathogens. This additional surveillance illustrates increased health-system strengthening. Furthermore, 34 countries reported an increased ability to use data in decision making; data-driven decisions are critical for improving local prevention and control of influenza around the world. PMID:27192395

  3. Prevention of influenza in healthy children

    PubMed Central

    Lee, Bruce Y; Shah, Mirat

    2013-01-01

    Healthy children are high transmitters of influenza and can experience poor influenza outcomes. Many questions remain about the efficacy and impect of preventive measures because most existing studies report imprecise proxies of influenza incidence, do not follow subjects throughout the entire influenza season and across multiple influenza seasons, or do not control for important factors such as timing of implementation and social contact patterns. Modeling and simulation are key methodologies to answer questions regarding influenza prevention. While vaccination may be the most efficacious existing intervention, variations in circulating strains and children’s immune systems keep current vaccines from being fully protective, necessitating further clinical and economic studies and technology improvements. Hand hygiene appears to be an important adjunct but improving compliance, standardizing regimens and quantifying its impact remain challenging. Future studies should help better define the specific indications and circumstances for antiviral use and the role of nutritional supplements and nonpharmaceutical interventions. PMID:23199400

  4. Influenza virus neuraminidase: structure, antibodies, and inhibitors.

    PubMed Central

    Colman, P. M.

    1994-01-01

    The determination of the 3-dimensional structure of the influenza virus neuraminidase in 1983 has served as a platform for understanding interactions between antibodies and protein antigens, for investigating antigenic variation in influenza viruses, and for devising new inhibitors of the enzyme. That work is reviewed here, together with more recent developments that have resulted in one of the inhibitors entering clinical trials as an anti-influenza virus drug. PMID:7849585

  5. Avian influenza: an osteopathic component to treatment

    PubMed Central

    Hruby, Raymond J; Hoffman, Keasha N

    2007-01-01

    Avian influenza is an infection caused by the H5N1 virus. The infection is highly contagious among birds, and only a few known cases of human avian influenza have been documented. However, healthcare experts around the world are concerned that mutation or genetic exchange with more commonly transmitted human influenza viruses could result in a pandemic of avian influenza. Their concern remains in spite of the fact that the first United States vaccine against the H5N1 virus was recently approved. Under these circumstances the fear is that a pandemic of avian influenza could result in the kind of mortality that was seen with the Spanish influenza pandemic of 1918–1919, where the number of deaths was estimated to be as high as 40 million people. Retrospective data gathered by the American Osteopathic Association shortly after the 1918–1919 influenza pandemic have suggested that osteopathic physicians (DOs), using their distinctive osteopathic manipulative treatment (OMT) methods, observed significantly lower morbidity and mortality among their patients as compared to those treated by allopathic physicians (MDs) with standard medical care available at the time. In light of the limited prevention and treatment options available, it seems logical that a preparedness plan for the treatment of avian influenza should include these OMT procedures, provided by DOs and other healthcare workers capable of being trained to perform these therapeutic interventions. The purpose of this paper is to discuss the characteristics of avian influenza, describe the success of DOs during the 1918–1919 Spanish influenza pandemic, describe the evidence base for the inclusion of OMT as part of the preparedness plan for the treatment of avian influenza, and describe some of the specific OMT procedures that could be utilized as part of the treatment protocol for avian influenza patients. PMID:17620133

  6. Interactions between the Influenza A Virus RNA Polymerase Components and Retinoic Acid-Inducible Gene I

    PubMed Central

    Li, Weizhong; Chen, Hongjun; Sutton, Troy; Obadan, Adebimpe

    2014-01-01

    ABSTRACT The influenza A virus genome possesses eight negative-strand RNA segments in the form of viral ribonucleoprotein particles (vRNPs) in association with the three viral RNA polymerase subunits (PB2, PB1, and PA) and the nucleoprotein (NP). Through interactions with multiple host factors, the RNP subunits play vital roles in replication, host adaptation, interspecies transmission, and pathogenicity. In order to gain insight into the potential roles of RNP subunits in the modulation of the host's innate immune response, the interactions of each RNP subunit with retinoic acid-inducible gene I protein (RIG-I) from mammalian and avian species were investigated. Studies using coimmunoprecipitation (co-IP), bimolecular fluorescence complementation (BiFc), and colocalization using confocal microscopy provided direct evidence for the RNA-independent binding of PB2, PB1, and PA with RIG-I from various hosts (human, swine, mouse, and duck). In contrast, the binding of NP with RIG-I was found to be RNA dependent. Expression of the viral NS1 protein, which interacts with RIG-I, did not interfere with the association of RNA polymerase subunits with RIG-I. The association of each individual virus polymerase component with RIG-I failed to significantly affect the interferon (IFN) induction elicited by RIG-I and 5′ triphosphate (5′ppp) RNA in reporter assays, quantitative reverse transcription-PCR (RT-PCR), and IRF3 phosphorylation tests. Taken together, these findings indicate that viral RNA polymerase components PB2, PB1, and PA directly target RIG-I, but the exact biological significance of these interactions in the replication and pathogenicity of influenza A virus needs to be further clarified. IMPORTANCE RIG-I is an important RNA sensor to elicit the innate immune response in mammals and some bird species (such as duck) upon influenza A virus infection. Although the 5′-triphosphate double-stranded RNA (dsRNA) panhandle structure at the end of viral genome RNA is

  7. Amaranth (Amaranthus hypochondriacus) vicilin subunit structure.

    PubMed

    Quiroga, Alejandra; Martínez, E Nora; Rogniaux, Hélène; Geairon, Audrey; Añón, M Cristina

    2010-12-22

    The 7S-globulin fraction is a minor component of the amaranth storage proteins. The present work provides new information about this protein. The amaranth 7S-globulin or vicilin presented a sedimentation coefficient of 8.6 ± 0.6 S and was composed of main subunits of 66, 52, 38, and 16 kDa. On the basis of mass spectrometry (MS) analysis of tryptic fragments, the 52, 38, and 16 kDa subunits presented sequence homology with sesame vicilin, whereas the 66 kDa subunit showed sequence similarity with a putative vicilin. Several characteristics of the 66 kDa subunit were similar to members of the convicilin family. Results support the hypothesis that the 7S-globulin molecules are composed of subunits coming from at least two gene families with primary products of 66 and 52 kDa, respectively. According to the present information, amaranth vicilin may be classified into the vicilin group that includes pea, broad bean, and sesame vicilins, among others. PMID:21117690

  8. Modulation of the skeletal muscle sodium channel alpha-subunit by the beta 1-subunit.

    PubMed

    Wallner, M; Weigl, L; Meera, P; Lotan, I

    1993-12-28

    Co-expression of cloned sodium channel beta 1-subunit with the rat skeletal muscle-subunit (alpha microI) accelerated the macroscopic current decay, enhanced the current amplitude, shifted the steady state inactivation curve to more negative potentials and decreased the time required for complete recovery from inactivation. Sodium channels expressed from skeletal muscle mRNA showed a similar behaviour to that observed from alpha microI/beta 1, indicating that beta 1 restores 'physiological' behaviour. Northern blot analysis revealed that the Na+ channel beta 1-subunit is present in high abundance (about 0.1%) in rat heart, brain and skeletal muscle, and the hybridization with untranslated region of the 'brain' beta 1 cDNA to skeletal muscle and heart mRNA indicated that the different Na+ channel alpha-subunits in brain, skeletal muscle and heart may share a common beta 1-subunit. PMID:8282123

  9. Influenza vaccination among the elderly in Italy.

    PubMed Central

    Pregliasco, F.; Sodano, L.; Mensi, C.; Selvaggi, M. T.; Adamo, B.; D'Argenio, P.; Giussani, F.; Simonetti, A.; Carosella, M. R.; Simeone, R.; Dentizi, C.; Montanaro, C.; Ponzio, G.

    1999-01-01

    This article surveys the attitudes and perceptions of a random sample of the elderly population in three regions of Italy on the use and efficacy of influenza vaccine. The data were collected by direct interviews using a standard questionnaire. The results show that vaccination coverage against influenza is inadequate (26-48.6%). The major reasons for nonvaccination were lack of faith in the vaccine and disbelief that influenza is a dangerous illness. These data emphasize the need for a systematic education programme targeted at the elderly and the provision of influenza vaccination, with the increased cooperation of general practitioners. PMID:10083710

  10. Virulence determinants of pandemic influenza viruses

    PubMed Central

    Tscherne, Donna M.; García-Sastre, Adolfo

    2011-01-01

    Influenza A viruses cause recurrent, seasonal epidemics and occasional global pandemics with devastating levels of morbidity and mortality. The ability of influenza A viruses to adapt to various hosts and undergo reassortment events ensures constant generation of new strains with unpredictable degrees of pathogenicity, transmissibility, and pandemic potential. Currently, the combination of factors that drives the emergence of pandemic influenza is unclear, making it impossible to foresee the details of a future outbreak. Identification and characterization of influenza A virus virulence determinants may provide insight into genotypic signatures of pathogenicity as well as a more thorough understanding of the factors that give rise to pandemics. PMID:21206092

  11. Modeling human influenza infection in the laboratory

    PubMed Central

    Radigan, Kathryn A; Misharin, Alexander V; Chi, Monica; Budinger, GR Scott

    2015-01-01

    Influenza is the leading cause of death from an infectious cause. Because of its clinical importance, many investigators use animal models to understand the biologic mechanisms of influenza A virus replication, the immune response to the virus, and the efficacy of novel therapies. This review will focus on the biosafety, biosecurity, and ethical concerns that must be considered in pursuing influenza research, in addition to focusing on the two animal models – mice and ferrets – most frequently used by researchers as models of human influenza infection. PMID:26357484

  12. RNA-Free and Ribonucleoprotein-Associated Influenza Virus Polymerases Directly Bind the Serine-5-Phosphorylated Carboxyl-Terminal Domain of Host RNA Polymerase II

    PubMed Central

    Martínez-Alonso, Mónica; Hengrung, Narin

    2016-01-01

    ABSTRACT Influenza viruses subvert the transcriptional machinery of their hosts to synthesize their own viral mRNA. Ongoing transcription by cellular RNA polymerase II (Pol II) is required for viral mRNA synthesis. By a process known as cap snatching, the virus steals short 5′ capped RNA fragments from host capped RNAs and uses them to prime viral transcription. An interaction between the influenza A virus RNA polymerase and the C-terminal domain (CTD) of the large subunit of Pol II has been established, but the molecular details of this interaction remain unknown. We show here that the influenza virus ribonucleoprotein (vRNP) complex binds to the CTD of transcriptionally engaged Pol II. Furthermore, we provide evidence that the viral polymerase binds directly to the serine-5-phosphorylated form of the Pol II CTD, both in the presence and in the absence of viral RNA, and show that this interaction is conserved in evolutionarily distant influenza viruses. We propose a model in which direct binding of the viral RNA polymerase in the context of vRNPs to Pol II early in infection facilitates cap snatching, while we suggest that binding of free viral polymerase to Pol II late in infection may trigger Pol II degradation. IMPORTANCE Influenza viruses cause yearly epidemics and occasional pandemics that pose a threat to human health, as well as represent a large economic burden to health care systems globally. Existing vaccines are not always effective, as they may not exactly match the circulating viruses. Furthermore, there are a limited number of antivirals available, and development of resistance to these is a concern. New measures to combat influenza are needed, but before they can be developed, it is necessary to better understand the molecular interactions between influenza viruses and their host cells. By providing further insights into the molecular details of how influenza viruses hijack the host transcriptional machinery, we aim to uncover novel targets for

  13. Economic benefits of inactivated influenza vaccines in the prevention of seasonal influenza in children

    PubMed Central

    Salleras, Luis; Navas, Encarna; Torner, Nuria; Prat, Andreu A.; Garrido, Patricio; Soldevila, Núria; Domínguez, Angela

    2013-01-01

    The aim of this study was to systematically review published studies that evaluated the efficiency of inactivated influenza vaccination in preventing seasonal influenza in children. The vaccine evaluated was the influenza-inactivated vaccine in 10 studies and the virosomal inactivated vaccine in 3 studies. The results show that yearly vaccination of children with the inactivated influenza vaccine saves money from the societal and family perspectives but not from the public or private provider perspective. When vaccination does not save money, the cost-effectiveness ratios were very acceptable. It can be concluded, that inactivated influenza vaccination of children is a very efficient intervention. PMID:23295894

  14. Subunit architecture of general transcription factor TFIIH.

    PubMed

    Gibbons, Brian J; Brignole, Edward J; Azubel, Maia; Murakami, Kenji; Voss, Neil R; Bushnell, David A; Asturias, Francisco J; Kornberg, Roger D

    2012-02-01

    Structures of complete 10-subunit yeast TFIIH and of a nested set of subcomplexes, containing 5, 6, and 7 subunits, have been determined by electron microscopy (EM) and 3D reconstruction. Consistency among all the structures establishes the location of the "minimal core" subunits (Ssl1, Tfb1, Tfb2, Tfb4, and Tfb5), and additional densities can be specifically attributed to Rad3, Ssl2, and the TFIIK trimer. These results can be further interpreted by placement of previous X-ray structures into the additional densities to give a preliminary picture of the RNA polymerase II preinitiation complex. In this picture, the key catalytic components of TFIIH, the Ssl2 ATPase/helicase and the Kin28 protein kinase are in proximity to their targets, downstream promoter DNA and the RNA polymerase C-terminal domain. PMID:22308316

  15. Heteromeric assembly of P2X subunits

    PubMed Central

    Saul, Anika; Hausmann, Ralf; Kless, Achim; Nicke, Annette

    2013-01-01

    Transcripts and/or proteins of P2X receptor (P2XR) subunits have been found in virtually all mammalian tissues. Generally more than one of the seven known P2X subunits have been identified in a given cell type. Six of the seven cloned P2X subunits can efficiently form functional homotrimeric ion channels in recombinant expression systems. This is in contrast to other ligand-gated ion channel families, such as the Cys-loop or glutamate receptors, where homomeric assemblies seem to represent the exception rather than the rule. P2XR mediated responses recorded from native tissues rarely match exactly the biophysical and pharmacological properties of heterologously expressed homomeric P2XRs. Heterotrimerization of P2X subunits is likely to account for this observed diversity. While the existence of heterotrimeric P2X2/3Rs and their role in physiological processes is well established, the composition of most other P2XR heteromers and/or the interplay between distinct trimeric receptor complexes in native tissues is not clear. After a description of P2XR assembly and the structure of the intersubunit ATP-binding site, this review summarizes the distribution of P2XR subunits in selected mammalian cell types and the biochemically and/or functionally characterized heteromeric P2XRs that have been observed upon heterologous co-expression of P2XR subunits. We further provide examples where the postulated heteromeric P2XRs have been suggested to occur in native tissues and an overview of the currently available pharmacological tools that have been used to discriminate between homo- and heteromeric P2XRs. PMID:24391538

  16. Live, attenuated influenza virus (LAIV) vehicles are strong inducers of immunity toward influenza B virus

    PubMed Central

    Huber, Victor C.; Kleimeyer, Loren H.; McCullers, Jonathan A.

    2008-01-01

    Historically, vaccines developed toward influenza viruses of the B type using methodologies developed for influenza A viruses as a blueprint have not been equally efficacious or effective. Because most influenza research and public attention concerns influenza A viruses, these shortcomings have not been adequately addressed. In this manuscript, we utilized different influenza vaccine vehicles to compare immunogenicity and protection in mice and ferrets after vaccination against an influenza B virus. We report that plasmid DNA vaccines demonstrate low immunogenicity profiles and poor protection compared to either whole, inactivated influenza virus (IIV) or, live, attenuated influenza virus (LAIV) vaccines. When mixed prime:boost regimens using LAIV and IIV were studied, we observed a boosting effect in mice after priming with LAIV that was not seen when IIV was used as the prime. In ferrets LAIV induced high antibody titers after a single dose and provided a boost in IIV-primed animals. Regimens including LAIV as a prime demonstrated enhanced protection, and adjuvantation was required for efficacy using the IIV preparation. Our results differ from generally accepted influenza A virus vaccine models, and argue that strategies for control of influenza B virus should be considered separately from those for influenza A virus. PMID:18708106

  17. Inhibition of influenza virus replication via small molecules that induce the formation of higher-order nucleoprotein oligomers.

    PubMed

    Gerritz, Samuel W; Cianci, Christopher; Kim, Sean; Pearce, Bradley C; Deminie, Carol; Discotto, Linda; McAuliffe, Brian; Minassian, Beatrice F; Shi, Shuhao; Zhu, Shirong; Zhai, Weixu; Pendri, Annapurna; Li, Guo; Poss, Michael A; Edavettal, Suzanne; McDonnell, Patricia A; Lewis, Hal A; Maskos, Klaus; Mörtl, Mario; Kiefersauer, Reiner; Steinbacher, Stefan; Baldwin, Eric T; Metzler, William; Bryson, James; Healy, Matthew D; Philip, Thomas; Zoeckler, Mary; Schartman, Richard; Sinz, Michael; Leyva-Grado, Victor H; Hoffmann, Hans-Heinrich; Langley, David R; Meanwell, Nicholas A; Krystal, Mark

    2011-09-13

    Influenza nucleoprotein (NP) plays multiple roles in the virus life cycle, including an essential function in viral replication as an integral component of the ribonucleoprotein complex, associating with viral RNA and polymerase within the viral core. The multifunctional nature of NP makes it an attractive target for antiviral intervention, and inhibitors targeting this protein have recently been reported. In a parallel effort, we discovered a structurally similar series of influenza replication inhibitors and show that they interfere with NP-dependent processes via formation of higher-order NP oligomers. Support for this unique mechanism is provided by site-directed mutagenesis studies, biophysical characterization of the oligomeric ligand:NP complex, and an X-ray cocrystal structure of an NP dimer of trimers (or hexamer) comprising three NP_A:NP_B dimeric subunits. Each NP_A:NP_B dimeric subunit contains two ligands that bridge two composite, protein-spanning binding sites in an antiparallel orientation to form a stable quaternary complex. Optimization of the initial screening hit produced an analog that protects mice from influenza-induced weight loss and mortality by reducing viral titers to undetectable levels throughout the course of treatment. PMID:21896751

  18. Inhibition of influenza virus replication via small molecules that induce the formation of higher-order nucleoprotein oligomers

    PubMed Central

    Gerritz, Samuel W.; Cianci, Christopher; Kim, Sean; Pearce, Bradley C.; Deminie, Carol; Discotto, Linda; McAuliffe, Brian; Minassian, Beatrice F.; Shi, Shuhao; Zhu, Shirong; Zhai, Weixu; Pendri, Annapurna; Poss, Michael A.; Edavettal, Suzanne; McDonnell, Patricia A.; Lewis, Hal A.; Maskos, Klaus; Mörtl, Mario; Kiefersauer, Reiner; Steinbacher, Stefan; Baldwin, Eric T.; Metzler, William; Bryson, James; Healy, Matthew D.; Philip, Thomas; Zoeckler, Mary; Schartman, Richard; Sinz, Michael; Leyva-Grado, Victor H.; Hoffmann, Hans-Heinrich; Langley, David R.; Meanwell, Nicholas A.; Krystal, Mark

    2011-01-01

    Influenza nucleoprotein (NP) plays multiple roles in the virus life cycle, including an essential function in viral replication as an integral component of the ribonucleoprotein complex, associating with viral RNA and polymerase within the viral core. The multifunctional nature of NP makes it an attractive target for antiviral intervention, and inhibitors targeting this protein have recently been reported. In a parallel effort, we discovered a structurally similar series of influenza replication inhibitors and show that they interfere with NP-dependent processes via formation of higher-order NP oligomers. Support for this unique mechanism is provided by site-directed mutagenesis studies, biophysical characterization of the oligomeric ligand:NP complex, and an X-ray cocrystal structure of an NP dimer of trimers (or hexamer) comprising three NP_A:NP_B dimeric subunits. Each NP_A:NP_B dimeric subunit contains two ligands that bridge two composite, protein-spanning binding sites in an antiparallel orientation to form a stable quaternary complex. Optimization of the initial screening hit produced an analog that protects mice from influenza-induced weight loss and mortality by reducing viral titers to undetectable levels throughout the course of treatment. PMID:21896751

  19. Oxidant regulated inter-subunit disulfide bond formation between ASIC1a subunits

    PubMed Central

    Zha, Xiang-ming; Wang, Runping; Collier, Dan M.; Snyder, Peter M.; Wemmie, John A.; Welsh, Michael J.

    2009-01-01

    The acid-sensing ion channel-1a (ASIC1a) is composed of 3 subunits and is activated by a decrease in extracellular pH. It plays an important role in diseases associated with a reduced pH and production of oxidants. Previous work showed that oxidants reduce ASIC1a currents. However, the effects on channel structure and composition are unknown. We found that ASIC1a formed inter-subunit disulfide bonds and the oxidant H2O2 increased this link between subunits. Cys-495 in the ASIC1a C terminus was particularly important for inter-subunit disulfide bond formation, although other C-terminal cysteines contributed. Inter-subunit disulfide bonds also produced some ASIC1a complexes larger than trimers. Inter-subunit disulfide bond formation reduced the proportion of ASIC1a located on the cell surface and contributed to the H2O2-induced decrease in H+-gated current. These results indicate that channel function is controlled by disulfide bond formation between intracellular residues on distinct ASIC1a subunits. They also suggest a mechanism by which the redox state can dynamically regulate membrane protein activity by forming intracellular bridges. PMID:19218436

  20. Transmission of influenza A viruses.

    PubMed

    Neumann, Gabriele; Kawaoka, Yoshihiro

    2015-05-01

    Influenza A viruses cause respiratory infections that range from asymptomatic to deadly in humans. Widespread outbreaks (pandemics) are attributable to 'novel' viruses that possess a viral hemagglutinin (HA) gene to which humans lack immunity. After a pandemic, these novel viruses form stable virus lineages in humans and circulate until they are replaced by other novel viruses. The factors and mechanisms that facilitate virus transmission among hosts and the establishment of novel lineages are not completely understood, but the HA and basic polymerase 2 (PB2) proteins are thought to play essential roles in these processes by enabling avian influenza viruses to infect mammals and replicate efficiently in their new host. Here, we summarize our current knowledge of the contributions of HA, PB2, and other viral components to virus transmission and the formation of new virus lineages. PMID:25812763

  1. Vitamin D and Influenza12

    PubMed Central

    Coleman, Laura A.

    2012-01-01

    Vitamin D has become increasingly recognized in the literature for its extra-skeletal roles, including an effect on inflammation and the immune response to infection. Our goal was to describe the role of vitamin D in the immune response and implications for the risk of influenza infection in humans. In this review, we first consider literature that provides molecular and genetic support to the idea that vitamin D is related to the adaptive and innate immune responses to influenza infection in vitro and in animal models. We then discuss observational studies and randomized controlled trials of vitamin D supplementation in humans. Finally, we consider some of the knowledge gaps surrounding vitamin D and immune response that must be filled. PMID:22797987

  2. Transmission of Influenza A Viruses

    PubMed Central

    Neumann, Gabriele; Kawaoka, Yoshihiro

    2015-01-01

    Influenza A viruses cause respiratory infections that range from asymptomatic to deadly in humans. Widespread outbreaks (pandemics) are attributable to ‘novel’ viruses that possess a viral hemagglutinin (HA) gene to which humans lack immunity. After a pandemic, these novel viruses form stable virus lineages in humans and circulate until they are replaced by other novel viruses. The factors and mechanisms that facilitate virus transmission among hosts and the establishment of novel lineages are not completely understood, but the HA and basic polymerase 2 (PB2) proteins are thought to play essential roles in these processes by enabling avian influenza viruses to infect mammals and replicate efficiently in their new host. Here, we summarize our current knowledge of the contributions of HA, PB2, and other viral components to virus transmission and the formation of new virus lineages. PMID:25812763

  3. Pandemic influenza planning by videoconference.

    PubMed

    Kimball, Ann Marie; Arima, Yuzo; French, H Matthew; Osaki, Carl S; Hoff, Rodney; Lee, Soo-Sim; Schafer, Lisa; Nabae, Koji; Chen, Chang-Hsun; Hsun, Chang; Hishamuddin, Pengiran; Nelson, Rodney; Woody, Karalee; Brown, Jacqueline; Fox, Louis

    2009-01-01

    Collaboration between nations and sectors is crucial to improve regional preparedness against pandemic influenza. In 2008, a Virtual Symposium was organized in the Asia-Pacific region by the Asia-Pacific Economic Cooperation Emerging Infections Network (APEC EINet) to discuss pandemic preparedness. The multipoint videoconference lasted approximately 4.5 hours and was attended by 16 APEC members who shared best practices in public-private partnerships for pandemic influenza preparedness planning. Twelve of the 16 APEC members who participated responded to a post-event survey. The overall experience of the event was rated highly. Partnering public health, technology and business communities to discuss best practices in preparedness using videoconferencing may be an effective way to improve regional preparedness. Utilization of videoconferencing on a routine basis should be considered to improve preparedness among APEC members and enhance its usability during a pandemic. PMID:19815907

  4. How Experience Shapes Health Beliefs: The Case of Influenza Vaccination

    ERIC Educational Resources Information Center

    Shahrabani, Shosh; Benzion, Uri

    2012-01-01

    This study examines the impact of past experience with influenza and the influenza vaccine on four categories of the Health Belief Model: beliefs about susceptibility to contracting influenza, severity of illness, perceived benefits of the vaccine in preventing influenza, and perceived barriers to getting vaccinated. The study population comprised…

  5. Cross-Protection of Influenza A Virus Infection by a DNA Aptamer Targeting the PA Endonuclease Domain

    PubMed Central

    Yuan, Shuofeng; Zhang, Naru; Singh, Kailash; Shuai, Huiping; Chu, Hin; Zhou, Jie; Chow, Billy K. C.

    2015-01-01

    Amino acid residues in the N-terminal of the PA subunit (PAN) of the influenza A virus polymerase play critical roles in endonuclease activity, protein stability, and viral RNA (vRNA) promoter binding. In addition, PAN is highly conserved among different subtypes of influenza virus, which suggests PAN to be a desired target in the development of anti-influenza agents. We selected DNA aptamers targeting the intact PA protein or the PAN domain of an H5N1 virus strain using systematic evolution of ligands by exponential enrichment (SELEX). The binding affinities of selected aptamers were measured, followed by an evaluation of in vitro endonuclease inhibitory activity. Next, the antiviral effects of enriched aptamers against influenza A virus infections were examined. A total of three aptamers targeting PA and six aptamers targeting PAN were selected. Our data demonstrated that all three PA-selected aptamers neither inhibited endonuclease activity nor exhibited antiviral efficacy, whereas four of the six PAN-selected aptamers inhibited both endonuclease activity and H5N1 virus infection. Among the four effective aptamers, one exhibited cross-protection against infections of H1N1, H5N1, H7N7, and H7N9 influenza viruses, with a 50% inhibitory concentration (IC50) of around 10 nM. Notably, this aptamer was identified at the 5th round but disappeared after the 10th round of selection, suggesting that the identification and evaluation of aptamers at early rounds of selection may be highly helpful for screening effective aptamers. Overall, our study provides novel insights for screening and developing effective aptamers for use as anti-influenza drugs. PMID:25918143

  6. Swine origin influenza (swine flu).

    PubMed

    Sebastian, Meghna R; Lodha, Rakesh; Kabra, S K

    2009-08-01

    Swine origin influenza was first recognized in the border area of Mexico and United States in April 2009 and during a short span of two months became the first pandemic. The currently circulating strain of swine origin influenza virus of the H1N1 strain has undergone triple reassortment and contains genes from the avian, swine and human viruses. It is transmitted by droplets or fomites. Incubation period is 2 to 7 days. Common clinical symptoms are indistinguishable by any viral respiratory illness, and include fever, cough, sore throat and myalgia. A feature seen more frequently with swine origin influenza is GI upset. Less than 10% of patients require hospitalization. Patients at risk of developing severe disease are - younger than five years, elderly, pregnant women, with chronic systemic illnesses, adolescents on aspirin. Of the severe manifestations of swine origin influenza, pneumonia and respiratory failure are the most common. Unusual symptoms reported are conjunctivitis, parotitis, hemophagocytic syndrome. Infants may present with fever and lethargy with no respiratory symptoms. Diagnosis is based on RT PCR, Viral culture or increasing neutralizing antibodies. Principle of treatment consist of isolation, universal precautions, good infection control practices, supportive care and use of antiviral drugs. Antiviral drugs effective against H1N1 virus include: oseltamivir and zamanavir. With good supportive care case fatality is less than 1%. Preventive measures include: social distancing, practicing respiratory etiquette, hand hygiene and use of chemoprohylaxis with antiviral drugs. Vaccine against H1N1 is not available at present, but will be available in near future. PMID:19802552

  7. Influenza vaccines for avian species.

    PubMed

    Kapczynski, Darrell R; Swayne, David E

    2009-01-01

    Beginning in Southeast Asia in 2003, a multinational epizootic outbreak of H5N1 highly pathogenic avian influenza (HPAI) was identified in commercial poultry and wild bird species. This lineage, originally identified in Southern China in 1996 and then Hong Kong in 1997, caused severe morbidity and mortality in many bird species, was responsible for considerable economic losses via trade restrictions, and crossed species barriers (including its recovery from human cases). To date, these H5N1 HPAI viruses have been isolated in European, Middle Eastern, and African countries, and are considered endemic in many areas where regulatory control and different production sectors face substantial hurdles in controlling the spread of this disease. While control of avian influenza (AI) virus infections in wild bird populations may not be feasible at this point, control and eradiation of AI from commercial, semicommercial, zoo, pet, and village/backyard birds will be critical to preventing events that could lead to the emergence of epizootic influenza virus. Efficacious vaccines can help reduce disease, viral shedding, and transmission to susceptible cohorts. However, only when vaccines are used in a comprehensive program including biosecurity, education, culling, diagnostics and surveillance can control and eradication be considered achievable goals. In humans, protection against influenza is provided by vaccines that are chosen based on molecular, epidemiologic, and antigenic data. In poultry and other birds, AI vaccines are produced against a specific hemagglutinin subtype of AI, and use is decided by government and state agricultural authorities based on risk and economic considerations, including the potential for trade restrictions. In the current H5N1 HPAI epizootic, vaccines have been used in a variety of avian species as a part of an overall control program to aid in disease management and control. PMID:19768403

  8. Coping with the influenza vaccine shortage.

    PubMed

    Mossad, Sherif B

    2004-12-01

    Faced with a shortage of the inactivated intramuscular influenza vaccine this year, the Centers for Disease Control and Prevention (CDC) has revised its guidelines for immunization and use of antiviral agents. The most rational solution at this time is to direct the supply of scarce vaccine to patients at highest risk of influenza-related complications. PMID:15641521

  9. 76 FR 4046 - Highly Pathogenic Avian Influenza

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-24

    ...We are amending the regulations concerning the importation of animals and animal products to prohibit or restrict the importation of bird and poultry products from regions where any subtype of highly pathogenic avian influenza is considered to exist. We are also adding restrictions concerning importation of live poultry and birds that have been vaccinated for certain types of avian influenza,......

  10. The global nature of avian influenza

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Avian influenza virus is a global virus which knows no geographic boundaries, has no political agenda, and can infect poultry irrespective of their agricultural or anthropocentric production systems. Avian influenza viruses or evidence of their infection have been detected in poultry and wild birds...

  11. Swine influenza virus: epidemiology and vaccine concerns

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Introduction. Swine influenza virus (SIV) is a primary cause of respiratory disease in swine and a component of the porcine respiratory disease complex (PRDC). Influenza viruses are an important health and economic concern for swine producers throughout the world. Swine operations may be affected by...

  12. Biology and transmission of avian influenza virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The natural host and reservoir for avian influenza is in wild birds where the viral infection is typically asymptomatic. The virus primarily replicates in the enteric tract and transmission is thought to be primarily by fecal-oral transmission. Avian influenza can infect a broad host range, but fo...

  13. Avian influenza diagnostics and surveillance methods

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The clinical presentation of avian influenza (AI) varies by virus strain and host species. The clinical disease and lesions the virus produces in poultry are not pathognomonic for avian influenza; therefore, diagnosis of AI virus (AIV) infection requires a laboratory test. Detection of AIV infecti...

  14. Avian influenza biology and disease transmission

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The natural host and reservoir for avian influenza is in wild birds where the viral infection is typically asymptomatic. The virus primarily replicates in the enteric tract and transmission is thought to be primarily by fecal oral transmission. Avian influenza can infect a broad host range, but fo...

  15. Pandemic Influenza Pediatric Office Plan Template

    SciTech Connect

    HCTT CHE

    2010-01-01

    This is a planning tool developed by pediatric stakeholders that is intended to assist pediatric medical offices that have no pandemic influenza plan in place, but may experience an increase in patient calls/visits or workload due to pandemic influenza.

  16. 77 FR 34783 - Highly Pathogenic Avian Influenza

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-12

    ... avian influenza (HPAI). On January 24, 2011, we published in the Federal Register (76 FR 4046-4056... Avian Influenza AGENCY: Animal and Plant Health Inspection Service, USDA. ACTION: Interim rule... importation of bird and poultry products from regions where any subtype of highly pathogenic avian...

  17. Avian influenza: preparedness and response strategies

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Avian influenza virus is naturally found in wild birds, primarily waterfowl, but the virus may also be found in poultry. In the United States we have a strong passive and active surveillance program for avian influenza in poultry. This includes serologic testing on most flocks that go through the ...

  18. A brief introduction to avian influenza virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Avian influenza virus (AIV) causes a disease of high economic importance for poultry production worldwide. The earliest recorded cases of probable high pathogenicity AIV in poultry were reported in Italy in the 1870’s and avian influenza been recognized in domestic poultry through the modern era of ...

  19. Summary of Control Issues for Swine Influenza

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Multiple subtypes of endemic swine influenza virus (SIV) co-circulate in the U.S. and Canada (H3N2, H1N1, and H1N2 with a triple reassortant internal gene (TRIG) constellation derived from swine, avian and human influenza viruses). As a result of reassortment events and antigenic drift, four H1 SIV...

  20. Influenza-Specific Antibody-Dependent Phagocytosis

    PubMed Central

    Ana-Sosa-Batiz, Fernanda; Vanderven, Hillary; Jegaskanda, Sinthujan; Johnston, Angus; Rockman, Steven; Laurie, Karen; Barr, Ian; Reading, Patrick; Lichtfuss, Marit; Kent, Stephen J.

    2016-01-01

    Background Immunity to human influenza A virus (IAV) infection is only partially understood. Broadly non-neutralizing antibodies may assist in reducing disease but have not been well characterized. Methods We measured internalization of opsonized, influenza protein-coated fluorescent beads and live IAV into a monocytic cell line to study antibody-dependent phagocytosis (ADP) against multiple influenza hemagglutinin (HA) subtypes. We analyzed influenza HA-specific ADP in healthy human donors, in preparations of intravenous immunoglobulin (IVIG), and following IAV infection of humans and macaques. Results We found that both sera from healthy adults and IVIG preparations had broad ADP to multiple seasonal HA proteins and weak cross-reactive ADP to non-circulating HA proteins. The ADP in experimentally influenza-infected macaque plasma and naturally influenza-infected human sera mediated phagocytosis of both homologous and heterologous IAVs. Further, the IAV phagocytosed in an antibody-mediated manner had reduced infectivity in vitro. Conclusion We conclude that IAV infections in humans and macaques leads to the development of influenza-specific ADP that can clear IAV infection in vitro. Repeated exposure of humans to multiple IAV infections likely leads to the development of ADP that is cross-reactive to strains not previously encountered. Further analyses of the protective capacity of broadly reactive influenza-specific ADP is warranted. PMID:27124730

  1. A brief introduction to avian influenza virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Avian influenza (AI) is caused by a type A influenza virus isolated from and adapted to an avian host. This chapter covers the basic physicochemical aspects of AIV including; virus family and properties, subtype classification; basic molecular biology and genetics. The avian host range and ecology...

  2. Subacute thyroiditis following seasonal influenza vaccination.

    PubMed

    Altay, Fatma Aybala; Güz, Galip; Altay, Mustafa

    2016-04-01

    A peritoneal dialysis patient who experienced a repeating attack after a vaccination for influenza while she was being followed and treated succesfully for subacute thyroiditis (SAT) is presented. This case shows SAT as a rare condition following vaccination.. Thus, SAT should be considered as a possible outcome following influenza vaccination and flu-like syndrome. PMID:26809709

  3. A polymorphic motif in the small subunit of ADP-glucose pyrophosphorylase modulates interactions between the small and large subunits.

    PubMed

    Cross, Joanna M; Clancy, Maureen; Shaw, Janine R; Boehlein, Susan K; Greene, Thomas W; Schmidt, Robert R; Okita, Thomas W; Hannah, L Curtis

    2005-02-01

    The heterotetrameric, allosterically regulated enzyme, adenosine-5'-diphosphoglucose pyrophosphorylase (AGPase) catalyzes the rate-limiting step in starch synthesis. Despite vast differences in allosteric properties and a long evolutionary separation, heterotetramers of potato small subunit and maize large subunit have activity comparable to either parent in an Escherichia coli expression system. In contrast, co-expression of maize small subunit with the potato large subunit produces little activity as judged by in vivo activity stain. To pinpoint the region responsible for differential activity, we expressed chimeric maize/potato small subunits in E. coli. This identified a 55-amino acid motif of the potato small subunit that is critical for glycogen production when expressed with the potato large subunit. Potato and maize small subunit sequences differ at five amino acids in this motif. Replacement experiments revealed that at least four amino acids of maize origin were required to reduce staining. An AGPase composed of a chimeric potato small subunit containing the 55-amino acid maize motif with the potato large subunit exhibited substantially less affinity for the substrates, glucose-1-phosphate and ATP and an increased Ka for the activator, 3-phosphoglyceric acid. Placement of the potato motif into the maize small subunit restored glycogen synthesis with the potato large subunit. Hence, a small polymorphic motif within the small subunit influences both catalytic and allosteric properties by modulating subunit interactions. PMID:15686515

  4. Intranasal Flu Vaccine Protective against Seasonal and H5N1 Avian Influenza Infections

    PubMed Central

    Alsharifi, Mohammed; Lobigs, Mario; Koskinen, Aulikki; Regner, Matthias; Trinidad, Lee; Boyle, David B.; Müllbacher, Arno

    2009-01-01

    Background Influenza A (flu) virus causes significant morbidity and mortality worldwide, and current vaccines require annual updating to protect against the rapidly arising antigenic variations due to antigenic shift and drift. In fact, current subunit or split flu vaccines rely exclusively on antibody responses for protection and do not induce cytotoxic T (Tc) cell responses, which are broadly cross-reactive between virus strains. We have previously reported that γ-ray inactivated flu virus can induce cross-reactive Tc cell responses. Methodology/Principal Finding Here, we report that intranasal administration of purified γ-ray inactivated human influenza A virus preparations (γ-Flu) effectively induces heterotypic and cross-protective immunity. A single intranasal administration of γ-A/PR8[H1N1] protects mice against lethal H5N1 and other heterotypic infections. Conclusions/Significance Intranasal γ-Flu represents a unique approach for a cross-protective vaccine against both seasonal as well as possible future pandemic influenza A virus infections. PMID:19401775

  5. Protection of mice against pandemic H1N1 influenza virus challenge after immunization with baculovirus-expressed stabilizing peptide fusion hemagglutinin protein.

    PubMed

    Yang, Eunji; Cho, Yonggeun; Choi, Jung-Ah; Choi, YoungJoo; Park, Pil-Gu; Park, Eunsun; Lee, Choong Hwan; Lee, Hyeja; Kim, Jongsun; Lee, Jae Myun; Song, Manki

    2015-02-01

    Current influenza vaccines are produced in embryonated chicken eggs. However, egg-based vaccines have various problems. To address these problems, recombinant protein vaccines have been developed as new vaccine candidates. Unfortunately, recombinant proteins frequently encounter aggregation and low stability during their biogenesis. It has been previously demonstrated that recombinantly expressed proteins can be greatly stabilized with high solubility by fusing stabilizing peptide (SP) derived from the C-terminal acidic tail of human synuclein (ATS). To investigate whether SP fusion proteins can induce protective immunity in mice, we produced influenza HA and SP fusion protein using a baculovirus expression system. In in vitro tests, SP-fused recombinant HA1 (SP-rHA1) was shown to be more stable than recombinant HA1 (rHA1). Mice were immunized intramuscularly with baculovirus-expressed rHA1 protein or SP-rHA1 protein (2 μg/mouse) formulated with aluminum hydroxide. Antibody responses were determined by ELISA and hemagglutination inhibition assay. We observed that SP-rHA1 immunization elicited HA-specific antibody responses that were comparable to rHA1 immunization. These results indicate that fusion of SP to rHA1 does not negatively affect the immunogenicity of the vaccine candidate. Therefore, it is possible to apply SP fusion technology to develop stable recombinant protein vaccines with high solubility. PMID:25394603

  6. Influenza Forecasting with Google Flu Trends

    PubMed Central

    Dugas, Andrea F.; Jalalpour, Mehdi; Gel, Yulia; Levin, Scott; Torcaso, Fred; Igusa, Takeru; Rothman, Richard

    2013-01-01

    Objective We sought to develop a practical influenza forecast model, based on real-time, geographically focused, and easy to access data, to provide individual medical centers with advanced warning of the number of influenza cases, thus allowing sufficient time to implement an intervention. Secondly, we evaluated how the addition of a real-time influenza surveillance system, Google Flu Trends, would impact the forecasting capabilities of this model. Introduction Each year, influenza results in increased Emergency Department crowding which can be mitigated through early detection linked to an appropriate response. Although current surveillance systems, such as Google Flu Trends, yield near real-time influenza surveillance, few demonstrate ability to forecast impending influenza cases. Methods Forecasting models designed to predict one week in advance were developed from weekly counts of confirmed influenza cases over seven seasons (2004 – 2011) divided into training and out-of-sample verification sets. Forecasting procedures using classical Box-Jenkins, generalized linear, and autoregressive methods were employed to develop the final model and assess the relative contribution of external variables such as, Google Flu Trends, meteorological data, and temporal information. Models were developed and evaluated through statistical measures of global deviance and log-likelihood ratio tests. An additional measure of forecast confidence, defined as the percentage of forecast values, during an influenza peak, that are within 7 influenza cases of the actual data, was examined to demonstrate practical utility of the model. Results A generalized autoregressive Poisson (GARMA) forecast model integrating previous influenza cases with Google Flu Trends information provided the most accurate influenza case predictions. Google Flu Trend data was the only source of external information providing significant forecast improvements (p = 0.00002). The final model, a GARMA intercept

  7. Influenza reverse genetics: dissecting immunity and pathogenesis.

    PubMed

    Ye, Siying; Evans, Justin G; Stambas, John

    2014-01-01

    Reverse genetics systems allow artificial generation of non-segmented and segmented negative-sense RNA viruses, like influenza viruses, entirely from cloned cDNA. Since the introduction of reverse genetics systems over a decade ago, the ability to generate 'designer' influenza viruses in the laboratory has advanced both basic and applied research, providing a powerful tool to investigate and characterise host-pathogen interactions and advance the development of novel therapeutic strategies. The list of applications for reverse genetics has expanded vastly in recent years. In this review, we discuss the development and implications of this technique, including the recent controversy surrounding the generation of a transmissible H5N1 influenza virus. We will focus on research involving the identification of viral protein function, development of live-attenuated influenza virus vaccines, host-pathogen interactions, immunity and the generation of recombinant influenza virus vaccine vectors for the prevention and treatment of infectious diseases and cancer. PMID:24528628

  8. Recommendations pertaining to the use of influenza vaccines and influenza antiviral drugs, 2016.

    PubMed

    Walaza, Sibongile; Cohen, Cheryl

    2016-03-01

    Vaccination is the most effective strategy to prevent influenza. It is recommended that influenza vaccine be administered each year before the influenza season, i.e. from March to June, although for individuals at increased risk of severe influenza in whom vaccination was missed, vaccine may be administered later. For a review of the 2015 influenza season and ongoing real-time updates of the 2016 influenza season when it starts, refer to the website of the National Institute for Communicable Diseases of the National Health Laboratory Service (www.nicd.ac.za). In this article we provide recommendations for the use of influenza vaccines in anticipation of the 2016 Southern Hemisphere influenza season. Guidance is based on available evidence to assist clinicians in making decisions regarding influenza vaccination. It should be noted that this article includes general recommendations for vaccination with influenza vaccines available in South Africa and may differ from groups targeted in specific vaccination programmes, e.g. the National Department of Health Programme. PMID:26915935

  9. Influenza vaccination coverage among medical residents

    PubMed Central

    Costantino, Claudio; Mazzucco, Walter; Azzolini, Elena; Baldini, Cesare; Bergomi, Margherita; Biafiore, Alessio Daniele; Bianco, Manuela; Borsari, Lucia; Cacciari, Paolo; Cadeddu, Chiara; Camia, Paola; Carluccio, Eugenia; Conti, Andrea; De Waure, Chiara; Di Gregori, Valentina; Fabiani, Leila; Fallico, Roberto; Filisetti, Barbara; Flacco, Maria E; Franco, Elisabetta; Furnari, Roberto; Galis, Veronica; Gallea, Maria R; Gallone, Maria F; Gallone, Serena; Gelatti, Umberto; Gilardi, Francesco; Giuliani, Anna R; Grillo, Orazio C; Lanati, Niccolò; Mascaretti, Silvia; Mattei, Antonella; Micò, Rocco; Morciano, Laura; Nante, Nicola; Napoli, Giuseppe; Nobile, Carmelo; Palladino, Raffaele; Parisi, Salvatore; Passaro, Maria; Pelissero, Gabriele; Quarto, Michele; Ricciardi, Walter; Romano, Gabriele; Rustico, Ennio; Saponari, Anita; Schioppa, Francesco S; Signorelli, Carlo; Siliquini, Roberta; Trabacchi, Valeria; Triassi, Maria; Varetta, Alessia; Ziglio, Andrea; Zoccali, Angela; Vitale, Francesco; Amodio, Emanuele

    2014-01-01

    Although influenza vaccination is recognized to be safe and effective, recent studies have confirmed that immunization coverage among health care workers remain generally low, especially among medical residents (MRs). Aim of the present multicenter study was to investigate attitudes and determinants associated with acceptance of influenza vaccination among Italian MRs. A survey was performed in 2012 on MRs attending post-graduate schools of 18 Italian Universities. Each participant was interviewed via an anonymous, self-administered, web-based questionnaire including questions on attitudes regarding influenza vaccination. A total of 2506 MRs were recruited in the survey and 299 (11.9%) of these stated they had accepted influenza vaccination in 2011–2012 season. Vaccinated MRs were older (P = 0.006), working in clinical settings (P = 0.048), and vaccinated in the 2 previous seasons (P < 0.001 in both seasons). Moreover, MRs who had recommended influenza vaccination to their patients were significantly more compliant with influenza vaccination uptake in 2011–2012 season (P < 0.001). “To avoid spreading influenza among patients” was recognized as the main reason for accepting vaccination by less than 15% of vaccinated MRs. Italian MRs seem to have a very low compliance with influenza vaccination and they seem to accept influenza vaccination as a habit that is unrelated to professional and ethical responsibility. Otherwise, residents who refuse vaccination in the previous seasons usually maintain their behaviors. Promoting correct attitudes and good practice in order to improve the influenza immunization rates of MRs could represent a decisive goal for increasing immunization coverage among health care workers of the future. PMID:24603089

  10. T cell recognition of the posttranslationally cleaved intersubunit region of influenza virus hemagglutinin.

    PubMed

    Rajnavölgyi, E; Nagy, Z; Kurucz, I; Gogolák, P; Tóth, G K; Váradi, G; Penke, B; Tigyi, Z; Hollósi, M; Gergely, J

    1994-12-01

    The influenza virus hemagglutinin is synthesized as a single polypeptide chain, but upon maturation it will posttranslationally be modified by a host cell related trypsin-like enzyme. The enzymatic cleavage attacks the so-called intersubunit region of the molecule giving rise to covalently linked HA1 and HA2 subunits. An I-Ed-restricted T cell epitope was identified in the highly conserved intact intersubunit region of the influenza virus hemagglutinin. T cell recognition of a 25-mer synthetic peptide comprising the intact intersubunit region does not require further processing and the elimination of the intervening Arg residue coupling the fusion peptide to the C-terminal segment of HA1 does not abolish the T cell activating capacity. The fine specificity pattern of a T cell hybridoma similar to that of the polyclonal T cell response demonstrates that a single T cell receptor is able to recognize peptides of different sizes representing not only the uncleaved but also the cleaved form of this hemagglutinin region. Based on specificity studies the epitope was localized to the C-terminal 11 amino acids of the HA1 subunit. The cross-reactivity of peptide-primed T cells with influenza virus infected antigen-presenting cells shows that fragments comprising the identified epitope of the intersubunit region can be generated as a result of natural processing of the hemagglutinin molecule. As antigen-presenting cells are lacking the enzyme which is responsible for the posttranslational modification of newly synthesized hemagglutinin molecules, the role of immature viral proteins in immune recognition is discussed. PMID:7823966

  11. Identification and characterization of a nontypeable Haemophilus influenzae putative toxin-antitoxin locus

    PubMed Central

    Daines, Dayle A; Jarisch, Justin; Smith, Arnold L

    2004-01-01

    Background Certain strains of an obligate parasite of the human upper respiratory tract, nontypeable Haemophilus influenzae (NTHi), can cause invasive diseases such as septicemia and meningitis, as well as chronic mucosal infections such as otitis media. To do this, the organism must invade and survive within both epithelial and endothelial cells. We have identified a facilitator of NTHi survival inside human cells, virulence-associated protein D (vapDHi, encoded by gene HI0450). Both vapDHi and a flanking gene, HI0451, exhibit the genetic and physical characteristics of a toxin/antitoxin (TA) locus, with VapDHi serving as the toxin moiety and HI0451 as the antitoxin. We propose the name VapXHi for the HI0451 antitoxin protein. Originally identified on plasmids, TA loci have been found on the chromosomes of a number of bacterial pathogens, and have been implicated in the control of translation during stressful conditions. Translation arrest would enhance survival within human cells and facilitate persistent or chronic mucosal infections. Results Isogenic mutants in vapDHi were attenuated for survival inside human respiratory epithelial cells (NCI-H292) and human brain microvascular endothelial cells (HBMEC), the in vitro models of mucosal infection and the blood-brain barrier, respectively. Transcomplementation with a vapDHi allele restored wild-type NTHi survival within both cell lines. A PCR survey of 59 H. influenzae strains isolated from various anatomical sites determined the presence of a vapDHiallele in 100% of strains. Two isoforms of the gene were identified in this population; one that was 91 residues in length, and another that was truncated to 45 amino acids due to an in-frame deletion. The truncated allele failed to transcomplement the NTHi vapDHi survival defect in HBMEC. Subunits of full-length VapDHi homodimerized, but subunits of the truncated protein did not. However, truncated protein subunits did interact with full-length subunits, and this

  12. Monitoring Avian Influenza A(H7N9) Virus through National Influenza-like Illness Surveillance, China

    PubMed Central

    Xu, Cuiling; Havers, Fiona; Wang, Lijie; Chen, Tao; Shi, Jinghong; Wang, Dayan; Yang, Jing; Yang, Lei; Widdowson, Marc-Alain

    2013-01-01

    In China during March 4–April 28, 2013, avian influenza A(H7N9) virus testing was performed on 20,739 specimens from patients with influenza-like illness in 10 provinces with confirmed human cases: 6 (0.03%) were positive, and increased numbers of unsubtypeable influenza-positive specimens were not seen. Careful monitoring and rapid characterization of influenza A(H7N9) and other influenza viruses remain critical. PMID:23879887

  13. Identification of Hsp90 as a species independent H5N1 avian influenza A virus PB2 interacting protein.

    PubMed

    Jirakanwisal, Krit; Srisutthisamphan, Kanjana; Thepparit, Chutima; Suptawiwat, Ornpreya; Auewarakul, Prasert; Paemanee, Atchara; Roytrakul, Sittiruk; Smith, Duncan R

    2015-12-01

    The avian influenza polymerase protein PB2 subunit is an important mediator of cross species adaptation and adaptation to mammalian cells is strongly but not exclusively associated with an adaptive mutation of the codon at position 627 of the PB2 protein which alters the glutamate normally found at this position to a lysine. This study sought to identify host cell factors in both mammalian and avian cells that interacted in a species specific or species independent manner. Two PB2 fusion proteins differing only in codon 627 were generated and transfected into mammalian and avian cells and interacting proteins identified through co-immunoprecipitation. A number of proteins including Hsp90 were identified and further investigation showed that Hsp90 interacted with both isoforms of PB2 in both mammalian and avian cells. Hsp90 is thus identified as a species independent interacting protein, further confirming that this protein may be a suitable target for anti-influenza drug development. PMID:26616658

  14. Peptide-Mediated Interference of PB2-eIF4G1 Interaction Inhibits Influenza A Viruses' Replication in Vitro and in Vivo.

    PubMed

    Yuan, Shuofeng; Chu, Hin; Ye, Jiahui; Hu, Meng; Singh, Kailash; Chow, Billy K C; Zhou, Jie; Zheng, Bo-Jian

    2016-07-01

    Influenza viruses are obligate parasites that hijack the host cellular system. Previous results have shown that the influenza virus PB2 subunit confers a dependence of host eukaryotic translation initiation factor 4-γ 1 (eIF4G1) for viral mRNA translation. Here, we demonstrated that peptide-mediated interference of the PB2-eIF4G1 interaction inhibited virus replication in vitro and in vivo. Remarkably, intranasal administration of the peptide provided 100% protection against lethal challenges of influenza A viruses in BALB/c mice, including H1N1, H5N1, and H7N9 influenza virus subtypes. Mapping of the PB2 protein indicated that the eIF4G1 binding sites resided within the PB2 cap-binding domain. Virtual docking analysis suggested that the inhibitory peptide associated with the conserved amino acid residues that were essential to PB2 cap-binding activity. Overall, our results identified the PB2-eIF4G1 interactive site as a druggable target for influenza therapeutics. PMID:27626099

  15. In Vivo Validation of Predicted and Conserved T Cell Epitopes in a Swine Influenza Model

    PubMed Central

    Gutiérrez, Andres H.; Loving, Crystal; Moise, Leonard; Terry, Frances E.; Brockmeier, Susan L.; Hughes, Holly R.; Martin, William D.; De Groot, Anne S.

    2016-01-01

    Swine influenza is a highly contagious respiratory viral infection in pigs that is responsible for significant financial losses to pig farmers annually. Current measures to protect herds from infection include: inactivated whole-virus vaccines, subunit vaccines, and alpha replicon-based vaccines. As is true for influenza vaccines for humans, these strategies do not provide broad protection against the diverse strains of influenza A virus (IAV) currently circulating in U.S. swine. Improved approaches to developing swine influenza vaccines are needed. Here, we used immunoinformatics tools to identify class I and II T cell epitopes highly conserved in seven representative strains of IAV in U.S. swine and predicted to bind to Swine Leukocyte Antigen (SLA) alleles prevalent in commercial swine. Epitope-specific interferon-gamma (IFNγ) recall responses to pooled peptides and whole virus were detected in pigs immunized with multi-epitope plasmid DNA vaccines encoding strings of class I and II putative epitopes. In a retrospective analysis of the IFNγ responses to individual peptides compared to predictions specific to the SLA alleles of cohort pigs, we evaluated the predictive performance of PigMatrix and demonstrated its ability to distinguish non-immunogenic from immunogenic peptides and to identify promiscuous class II epitopes. Overall, this study confirms the capacity of PigMatrix to predict immunogenic T cell epitopes and demonstrate its potential for use in the design of epitope-driven vaccines for swine. Additional studies that match the SLA haplotype of animals with the study epitopes will be required to evaluate the degree of immune protection conferred by epitope-driven DNA vaccines in pigs. PMID:27411061

  16. Structural Basis for Suppression of a Host Antiviral Response by Influenza A Virus

    SciTech Connect

    Das,K.; Ma, L.; Xiao, R.; Radvansky, B.; Aramini, J.; Zhao, L.; Marklund, J.; Kuo, R.; Twu, K.; Arnold, E.

    2008-01-01

    Influenza A viruses are responsible for seasonal epidemics and high mortality pandemics. A major function of the viral NS1A protein, a virulence factor, is the inhibition of the production of IFN-{beta}{beta} mRNA and other antiviral mRNAs. The NS1A protein of the human influenza A/Udorn/72 (Ud) virus inhibits the production of these antiviral mRNAs by binding the cellular 30-kDa subunit of the cleavage and polyadenylation specificity factor (CPSF30), which is required for the 3' end processing of all cellular pre-mRNAs. Here we report the 1.95- Angstroms resolution X-ray crystal structure of the complex formed between the second and third zinc finger domain (F2F3) of CPSF30 and the C-terminal domain of the Ud NS1A protein. The complex is a tetramer, in which each of two F2F3 molecules wraps around two NS1A effector domains that interact with each other head-to-head. This structure identifies a CPSF30 binding pocket on NS1A comprised of amino acid residues that are highly conserved among human influenza A viruses. Single amino acid changes within this binding pocket eliminate CPSF30 binding, and a recombinant Ud virus expressing an NS1A protein with such a substitution is attenuated and does not inhibit IFN-{beta} pre-mRNA processing. This binding pocket is a potential target for antiviral drug development. The crystal structure also reveals that two amino acids outside of this pocket, F103 and M106, which are highly conserved (>99%) among influenza A viruses isolated from humans, participate in key hydrophobic interactions with F2F3 that stabilize the complex.

  17. PKA regulatory subunit expression in tooth development.

    PubMed

    de Sousa, Sílvia Ferreira; Kawasaki, Katsushige; Kawasaki, Maiko; Volponi, Ana Angelova; Gomez, Ricardo Santiago; Gomes, Carolina Cavaliéri; Sharpe, Paul T; Ohazama, Atsushi

    2014-05-01

    Protein kinase A (PKA) plays critical roles in many biological processes including cell proliferation, cell differentiation, cellular metabolism and gene regulation. Mutation in PKA regulatory subunit, PRKAR1A has previously been identified in odontogenic myxomas, but it is unclear whether PKA is involved in tooth development. The aim of the present study was to assess the expression of alpha isoforms of PKA regulatory subunit (Prkar1a and Prkar2a) in mouse and human odontogenesis by in situ hybridization. PRKAR1A and PRKAR2A mRNA transcription was further confirmed in a human deciduous germ by qRT-PCR. Mouse Prkar1a and human PRKAR2A exhibited a dynamic spatio-temporal expression in tooth development, whereas neither human PRKAR1A nor mouse Prkar2a showed their expression in odontogenesis. These isoforms thus showed different expression pattern between human and mouse tooth germs. PMID:24755349

  18. Recent Advances in Subunit Vaccine Carriers

    PubMed Central

    Vartak, Abhishek; Sucheck, Steven J.

    2016-01-01

    The lower immunogenicity of synthetic subunit antigens, compared to live attenuated vaccines, is being addressed with improved vaccine carriers. Recent reports indicate that the physio-chemical properties of these carriers can be altered to achieve optimal antigen presentation, endosomal escape, particle bio-distribution, and cellular trafficking. The carriers can be modified with various antigens and ligands for dendritic cells targeting. They can also be modified with adjuvants, either covalently or entrapped in the matrix, to improve cellular and humoral immune responses against the antigen. As a result, these multi-functional carrier systems are being explored for use in active immunotherapy against cancer and infectious diseases. Advancing technology, improved analytical methods, and use of computational methodology have also contributed to the development of subunit vaccine carriers. This review details recent breakthroughs in the design of nano-particulate vaccine carriers, including liposomes, polymeric nanoparticles, and inorganic nanoparticles. PMID:27104575

  19. Recent Advances in Subunit Vaccine Carriers.

    PubMed

    Vartak, Abhishek; Sucheck, Steven J

    2016-01-01

    The lower immunogenicity of synthetic subunit antigens, compared to live attenuated vaccines, is being addressed with improved vaccine carriers. Recent reports indicate that the physio-chemical properties of these carriers can be altered to achieve optimal antigen presentation, endosomal escape, particle bio-distribution, and cellular trafficking. The carriers can be modified with various antigens and ligands for dendritic cells targeting. They can also be modified with adjuvants, either covalently or entrapped in the matrix, to improve cellular and humoral immune responses against the antigen. As a result, these multi-functional carrier systems are being explored for use in active immunotherapy against cancer and infectious diseases. Advancing technology, improved analytical methods, and use of computational methodology have also contributed to the development of subunit vaccine carriers. This review details recent breakthroughs in the design of nano-particulate vaccine carriers, including liposomes, polymeric nanoparticles, and inorganic nanoparticles. PMID:27104575

  20. Global Seasonal Influenza Epidemics and Climate

    NASA Astrophysics Data System (ADS)

    Tamerius, James

    2013-04-01

    Recent evidence suggests that low specific humidity conditions facilitate the transmission of the influenza virus in temperate regions and result in annual winter epidemics. However, this relationship does not account for the epidemiology of influenza in tropical and subtropical regions where epidemics often occur during the rainy season or transmit year-round without a well-defined season. We assessed the role of specific humidity and other local climatic variables on influenza virus seasonality by modeling epidemiological and climatic information from 78 study sites sampled globally. We substantiated that there are two types of environmental conditions associated with seasonal influenza epidemics: "cold-dry" and "humid-rainy". For sites where monthly average specific humidity or temperature decreases below thresholds of approximately 11-12 g/kg and 18-21 °C during the year, influenza activity peaks during the cold-dry season (i.e., winter) when specific humidity and temperature are at minimal levels. For sites where specific humidity and temperature do not decrease below these thresholds, seasonal influenza activity is more likely to peak in months when average precipitation totals are maximal and greater than 150 mm per month. Based on these findings, we develop Susceptible-Exposed-Infected-Recovered-Susceptible (SEIRS) models forced by daily weather observations of specific humidity and precipitation that simulate the diversity of seasonal influenza signals worldwide.

  1. Increasing herd immunity with influenza revaccination.

    PubMed

    Mooring, E Q; Bansal, S

    2016-04-01

    Seasonal influenza is a significant public health concern globally. While influenza vaccines are the single most effective intervention to reduce influenza morbidity and mortality, there is considerable debate surrounding the merits and consequences of repeated seasonal vaccination. Here, we describe a two-season influenza epidemic contact network model and use it to demonstrate that increasing the level of continuity in vaccination across seasons reduces the burden on public health. We show that revaccination reduces the influenza attack rate not only because it reduces the overall number of susceptible individuals, but also because it better protects highly connected individuals, who would otherwise make a disproportionately large contribution to influenza transmission. We also demonstrate that our results hold on an empirical contact network, in the presence of assortativity in vaccination status, and are robust for a range of vaccine coverage and efficacy levels. Our work contributes a population-level perspective to debates about the merits of repeated influenza vaccination and advocates for public health policy to incorporate individual vaccine histories. PMID:26482721

  2. Memory CD4 T cells in influenza.

    PubMed

    Zens, Kyra D; Farber, Donna L

    2015-01-01

    Influenza A virus is a significant cause of morbidity and mortality worldwide, particularly among young children and the elderly. Current vaccines induce neutralizing antibody responses directed toward highly variable viral surface proteins, resulting in limited heterosubtypic protection to new viral serotypes. By contrast, memory CD4 T cells recognize conserved viral proteins and are cross-reactive to multiple influenza strains. In humans, virus-specific memory CD4 T cells were found to be the protective correlate in human influenza challenge studies, suggesting their key role in protective immunity. In mouse models, memory CD4 T cells can mediate protective responses to secondary influenza infection independent of B cells or CD8 T cells, and can influence innate immune responses. Importantly, a newly defined, tissue-resident CD4 memory population has been demonstrated to be retained in lung tissue and promote optimal protective responses to an influenza infection. Here, we review the current state of results regarding the generation of memory CD4 T cells following primary influenza infection, mechanisms for their enhanced efficacy in protection from secondary challenge including their phenotype, localization, and function in the context of both mouse models and human infection. We also discuss the generation of memory CD4 T cells in response to influenza vaccines and its future implications for vaccinology. PMID:25005927

  3. Vaccination against influenza in pregnant women.

    PubMed

    Brydak, Lidia Bernadeta; Nitsch-Osuch, Aneta

    2014-01-01

    Pregnancy places otherwise healthy women at an increased risk of complications arising from an influenza infection. It is suggested that physiological changes such as immunological changes, increased cardiac output and oxygen consumption, as well as lung tidal volume might increase the susceptibility to influenza complications if infection occurs during pregnancy. Immunization of pregnant women against influenza is currently recommended in many countries and has been proven to be safe and effective in reducing rates and severity of the disease in vaccinated mothers and their children. Influenza vaccination is also cost-effective. Nevertheless, influenza vaccine coverage remains low in pregnant women. This might stem from the lack of healthcare workers' education, a feeling among the general public that influenza is not a serious disease and a failure of prenatal care providers to offer the vaccine. In order to protect pregnant women and infants from influenza related morbidity and mortality an educational programme targeting healthcare workers in charge of pregnant women should be implemented. PMID:25195141

  4. Economic and policy implications of pandemic influenza.

    SciTech Connect

    Smith, Braeton J.; Starks, Shirley J.; Loose, Verne W.; Brown, Theresa Jean; Warren, Drake E.; Vargas, Vanessa N.

    2010-03-01

    Pandemic influenza has become a serious global health concern; in response, governments around the world have allocated increasing funds to containment of public health threats from this disease. Pandemic influenza is also recognized to have serious economic implications, causing illness and absence that reduces worker productivity and economic output and, through mortality, robs nations of their most valuable assets - human resources. This paper reports two studies that investigate both the short- and long-term economic implications of a pandemic flu outbreak. Policy makers can use the growing number of economic impact estimates to decide how much to spend to combat the pandemic influenza outbreaks. Experts recognize that pandemic influenza has serious global economic implications. The illness causes absenteeism, reduced worker productivity, and therefore reduced economic output. This, combined with the associated mortality rate, robs nations of valuable human resources. Policy makers can use economic impact estimates to decide how much to spend to combat the pandemic influenza outbreaks. In this paper economists examine two studies which investigate both the short- and long-term economic implications of a pandemic influenza outbreak. Resulting policy implications are also discussed. The research uses the Regional Economic Modeling, Inc. (REMI) Policy Insight + Model. This model provides a dynamic, regional, North America Industrial Classification System (NAICS) industry-structured framework for forecasting. It is supported by a population dynamics model that is well-adapted to investigating macro-economic implications of pandemic influenza, including possible demand side effects. The studies reported in this paper exercise all of these capabilities.

  5. Structural basis of influenza virus neutralization

    PubMed Central

    Han, Thomas; Marasco, Wayne A.

    2010-01-01

    Although seasonal influenza vaccines play a valuable role in reducing the spread of the virus at the population level, ongoing viral evolution to evade immune responses remains problematic. No current vaccines are likely to elicit enduring protection in the face of emerging and re-emerging influenza viruses that rapidly undergoing antigenic drift. Eliciting broadly cross-neutralizing antibody responses against influenza virus is a crucial goal for seasonal and pandemic influenza vaccine preparation. Recent three-dimensional structure information obtained from crystallization of influenza antigens in complex with neutralizing antibodies (nAbs) have provided a framework for interpreting antibody-based viral neutralization that should aid in the design of vaccine immunogens. Here, we will review current knowledge of the structure-based mechanisms contributing to the neutralization and neutralization escape of influenza viruses. We will also explore the potential for this structure-based approach to overcome the challenge of obtaining the highly desired “universal” influenza vaccine. PMID:21251008

  6. The evolution of human influenza viruses.

    PubMed Central

    Hay, A J; Gregory, V; Douglas, A R; Lin, Y P

    2001-01-01

    The evolution of influenza viruses results in (i) recurrent annual epidemics of disease that are caused by progressive antigenic drift of influenza A and B viruses due to the mutability of the RNA genome and (ii) infrequent but severe pandemics caused by the emergence of novel influenza A subtypes to which the population has little immunity. The latter characteristic is a consequence of the wide antigenic diversity and peculiar host range of influenza A viruses and the ability of their segmented RNA genomes to undergo frequent genetic reassortment (recombination) during mixed infections. Contrasting features of the evolution of recently circulating influenza AH1N1, AH3N2 and B viruses include the rapid drift of AH3N2 viruses as a single lineage, the slow replacement of successive antigenic variants of AH1N1 viruses and the co-circulation over some 25 years of antigenically and genetically distinct lineages of influenza B viruses. Constant monitoring of changes in the circulating viruses is important for maintaining the efficacy of influenza vaccines in combating disease. PMID:11779385

  7. Influenza and pregnancy: a review of the literature from India.

    PubMed

    Bhalerao-Gandhi, Ashwini; Chhabra, Pankdeep; Arya, Saurabh; Simmerman, James Mark

    2015-01-01

    Maternal influenza infection is known to cause substantial morbidity and mortality among pregnant women and young children. Many professional healthcare bodies including the World Health Organization (WHO) have identified pregnant women as a priority risk group for receipt of inactivated seasonal influenza vaccination. However influenza prevention in this group is not yet a public health priority in India. This literature review was undertaken to examine the Indian studies of influenza among pregnant women. Eight Indian studies describing influenza burden and/or outcomes among pregnant women with influenza were identified. In most studies, influenza A (pH1N1) was associated with increased maternal mortality (25-75%), greater disease severity, and adverse fetal outcomes as compared to nonpregnant women. Surveillance for seasonal influenza infections along with higher quality prospective studies among pregnant women is needed to quantify disease burden, improve awareness among antenatal care providers, and formulate antenatal influenza vaccine policies. PMID:25810687

  8. The Global Transmission and Control of Influenza

    PubMed Central

    Matrajt, Laura; Halloran, M. Elizabeth; Longini, Ira M.

    2011-01-01

    New strains of influenza spread around the globe via the movement of infected individuals. The global dynamics of influenza are complicated by different patterns of influenza seasonality in different regions of the world. We have released an open-source stochastic mathematical model of the spread of influenza across 321 major, strategically located cities of the world. Influenza is transmitted between cities via infected airline passengers. Seasonality is simulated by increasing the transmissibility in each city at the times of the year when influenza has been observed to be most prevalent. The spatiotemporal spread of pandemic influenza can be understood through clusters of global transmission and links between them, which we identify using the epidemic percolation network (EPN) of the model. We use the model to explain the observed global pattern of spread for pandemic influenza A(H1N1) 2009–2010 (pandemic H1N1 2009) and to examine possible global patterns of spread for future pandemics depending on the origin of pandemic spread, time of year of emergence, and basic reproductive number (). We also use the model to investigate the effectiveness of a plausible global distribution of vaccine for various pandemic scenarios. For pandemic H1N1 2009, we show that the biggest impact of vaccination was in the temperate northern hemisphere. For pandemics starting in the temperate northern hemisphere in May or April, vaccination would have little effect in the temperate southern hemisphere and a small effect in the tropics. With the increasing interconnectedness of the world's population, we must take a global view of infectious disease transmission. Our open-source, computationally simple model can help public health officials plan for the next pandemic as well as deal with interpandemic influenza. PMID:21573121

  9. Universal influenza vaccines: Shifting to better vaccines.

    PubMed

    Berlanda Scorza, Francesco; Tsvetnitsky, Vadim; Donnelly, John J

    2016-06-01

    Influenza virus causes acute upper and lower respiratory infections and is the most likely, among known pathogens, to cause a large epidemic in humans. Influenza virus mutates rapidly, enabling it to evade natural and vaccine-induced immunity. Furthermore, influenza viruses can cross from animals to humans, generating novel, potentially pandemic strains. Currently available influenza vaccines induce a strain specific response and may be ineffective against new influenza viruses. The difficulty in predicting circulating strains has frequently resulted in mismatch between the annual vaccine and circulating viruses. Low-resource countries remain mostly unprotected against seasonal influenza and are particularly vulnerable to future pandemics, in part, because investments in vaccine manufacturing and stockpiling are concentrated in high-resource countries. Antibodies that target conserved sites in the hemagglutinin stalk have been isolated from humans and shown to confer protection in animal models, suggesting that broadly protective immunity may be possible. Several innovative influenza vaccine candidates are currently in preclinical or early clinical development. New technologies include adjuvants, synthetic peptides, virus-like particles (VLPs), DNA vectors, messenger RNA, viral vectors, and attenuated or inactivated influenza viruses. Other approaches target the conserved exposed epitope of the surface exposed membrane matrix protein M2e. Well-conserved influenza proteins, such as nucleoprotein and matrix protein, are mainly targeted for developing strong cross-protective T cell responses. With multiple vaccine candidates moving along the testing and development pipeline, the field is steadily moving toward a product that is more potent, durable, and broadly protective than previously licensed vaccines. PMID:27038130

  10. The global transmission and control of influenza.

    PubMed

    Kenah, Eben; Chao, Dennis L; Matrajt, Laura; Halloran, M Elizabeth; Longini, Ira M

    2011-01-01

    New strains of influenza spread around the globe via the movement of infected individuals. The global dynamics of influenza are complicated by different patterns of influenza seasonality in different regions of the world. We have released an open-source stochastic mathematical model of the spread of influenza across 321 major, strategically located cities of the world. Influenza is transmitted between cities via infected airline passengers. Seasonality is simulated by increasing the transmissibility in each city at the times of the year when influenza has been observed to be most prevalent. The spatiotemporal spread of pandemic influenza can be understood through clusters of global transmission and links between them, which we identify using the epidemic percolation network (EPN) of the model. We use the model to explain the observed global pattern of spread for pandemic influenza A(H1N1) 2009-2010 (pandemic H1N1 2009) and to examine possible global patterns of spread for future pandemics depending on the origin of pandemic spread, time of year of emergence, and basic reproductive number (). We also use the model to investigate the effectiveness of a plausible global distribution of vaccine for various pandemic scenarios. For pandemic H1N1 2009, we show that the biggest impact of vaccination was in the temperate northern hemisphere. For pandemics starting in the temperate northern hemisphere in May or April, vaccination would have little effect in the temperate southern hemisphere and a small effect in the tropics. With the increasing interconnectedness of the world's population, we must take a global view of infectious disease transmission. Our open-source, computationally simple model can help public health officials plan for the next pandemic as well as deal with interpandemic influenza. PMID:21573121

  11. Staggering of subunits in NMDAR channels.

    PubMed Central

    Sobolevsky, Alexander I; Rooney, LeeAnn; Wollmuth, Lonnie P

    2002-01-01

    Functional N-methyl-D-aspartate receptors (NMDARs) are heteromultimers formed by NR1 and NR2 subunits. The M3 segment, as contributed by NR1, forms the core of the extracellular vestibule, including binding sites for channel blockers, and represents a critical molecular link between ligand binding and channel opening. Taking advantage of the substituted cysteine accessibility method along with channel block and multivalent coordination, we studied the contribution of the M3 segment in NR2C to the extracellular vestibule. We find that the M3 segment in NR2C, like that in NR1, contributes to the core of the extracellular vestibule. However, the M3 segments from the two subunits are staggered relative to each other in the vertical axis of the channel. Compared to NR1, homologous positions in NR2C, including those in the highly conserved SYTANLAAF motif, are located about four amino acids more externally. The staggering of subunits may represent a key structural feature underlying the distinct functional properties of NMDARs. PMID:12496098

  12. Characterization of influenza virus among influenza like illness cases in Mumbai, India.

    PubMed

    Roy, Soumen; Dahake, Ritwik; Patil, Deepak; Tawde, Shweta; Mukherjee, Sandeepan; Athlekar, Shrikant; Chowdhary, Abhay; Deshmukh, Ranjana

    2014-01-01

    The present study was carried out to monitor influenza viruses by identifying the virus and studying the seasonal variation during 2007-2009 in Mumbai. A total of 193 clinical respiratory samples (nasal and throat swab) were collected from patients having influenza like illness in Mumbai region. One-step real-time reverse-transcriptase PCR (rRTPCR) was used to detect Influenza type A (H1 and H3) and Influenza type B virus. Isolation of the virus was carried out using in vitro system which was further confirmed and typed by hemagglutination assay and hemagglutination inhibition assay. Out of 193 samples 24 (12.4 3%) samples tested positive for influenza virus, of which 13 (6.73 %) were influenza type A virus and 10 (5.18 %) were influenza type B virus, while 1 sample (0.51 %) was positive for both. By culture methods, 3 (1.55 %) viral isolates were obtained. All the three isolates were found to be Influenza type B/Malaysia (Victoria lineage) by Hemagglutination Inhibition Assay. The data generated from the present study reveals that both Influenza type A and B are prevalent in Mumbai with considerable activity. The peak activity was observed during monsoon season. PMID:25674606

  13. National and local influenza surveillance through Twitter: an analysis of the 2012-2013 influenza epidemic.

    PubMed

    Broniatowski, David A; Paul, Michael J; Dredze, Mark

    2013-01-01

    Social media have been proposed as a data source for influenza surveillance because they have the potential to offer real-time access to millions of short, geographically localized messages containing information regarding personal well-being. However, accuracy of social media surveillance systems declines with media attention because media attention increases "chatter" - messages that are about influenza but that do not pertain to an actual infection - masking signs of true influenza prevalence. This paper summarizes our recently developed influenza infection detection algorithm that automatically distinguishes relevant tweets from other chatter, and we describe our current influenza surveillance system which was actively deployed during the full 2012-2013 influenza season. Our objective was to analyze the performance of this system during the most recent 2012-2013 influenza season and to analyze the performance at multiple levels of geographic granularity, unlike past studies that focused on national or regional surveillance. Our system's influenza prevalence estimates were strongly correlated with surveillance data from the Centers for Disease Control and Prevention for the United States (r = 0.93, p < 0.001) as well as surveillance data from the Department of Health and Mental Hygiene of New York City (r = 0.88, p < 0.001). Our system detected the weekly change in direction (increasing or decreasing) of influenza prevalence with 85% accuracy, a nearly twofold increase over a simpler model, demonstrating the utility of explicitly distinguishing infection tweets from other chatter. PMID:24349542

  14. National and Local Influenza Surveillance through Twitter: An Analysis of the 2012-2013 Influenza Epidemic

    PubMed Central

    Broniatowski, David A.; Paul, Michael J.; Dredze, Mark

    2013-01-01

    Social media have been proposed as a data source for influenza surveillance because they have the potential to offer real-time access to millions of short, geographically localized messages containing information regarding personal well-being. However, accuracy of social media surveillance systems declines with media attention because media attention increases “chatter” – messages that are about influenza but that do not pertain to an actual infection – masking signs of true influenza prevalence. This paper summarizes our recently developed influenza infection detection algorithm that automatically distinguishes relevant tweets from other chatter, and we describe our current influenza surveillance system which was actively deployed during the full 2012-2013 influenza season. Our objective was to analyze the performance of this system during the most recent 2012–2013 influenza season and to analyze the performance at multiple levels of geographic granularity, unlike past studies that focused on national or regional surveillance. Our system’s influenza prevalence estimates were strongly correlated with surveillance data from the Centers for Disease Control and Prevention for the United States (r = 0.93, p < 0.001) as well as surveillance data from the Department of Health and Mental Hygiene of New York City (r = 0.88, p < 0.001). Our system detected the weekly change in direction (increasing or decreasing) of influenza prevalence with 85% accuracy, a nearly twofold increase over a simpler model, demonstrating the utility of explicitly distinguishing infection tweets from other chatter. PMID:24349542

  15. Adenovirus as a carrier for the development of influenza virus-free avian influenza vaccines

    PubMed Central

    Tang, De-chu C; Zhang, Jianfeng; Toro, Haroldo; Shi, Zhongkai; Van Kampen, Kent R

    2009-01-01

    A long-sought goal during the battle against avian influenza is to develop a new generation of vaccines capable of mass immunizing humans as well as poultry (the major source of avian influenza for human infections) in a timely manner. Although administration of the currently licensed influenza vaccine is effective in eliciting protective immunity against seasonal influenza, this approach is associated with a number of insurmountable problems for preventing an avian influenza pandemic. Many of the hurdles may be eliminated by developing new avian influenza vaccines that do not require the propagation of an influenza virus during vaccine production. Replication-competent adenovirus-free adenovirus vectors hold promise as a carrier for influenza virus-free avian influenza vaccines owing to their safety profile and rapid manufacture using cultured suspension cells in a serum-free medium. Simple and efficient mass-immunization protocols, including nasal spray for people and automated in ovo vaccination for poultry, convey another advantage for this class of vaccines. In contrast to parenteral injection of adenovirus vector, the potency of adenovirus-vectored nasal vaccine is not appreciably interfered by pre-existing immunity to adenovirus. PMID:19348562

  16. Modeling Influenza Virus Infection: A Roadmap for Influenza Research

    PubMed Central

    Boianelli, Alessandro; Nguyen, Van Kinh; Ebensen, Thomas; Schulze, Kai; Wilk, Esther; Sharma, Niharika; Stegemann-Koniszewski, Sabine; Bruder, Dunja; Toapanta, Franklin R.; Guzmán, Carlos A.; Meyer-Hermann, Michael; Hernandez-Vargas, Esteban A.

    2015-01-01

    Influenza A virus (IAV) infection represents a global threat causing seasonal outbreaks and pandemics. Additionally, secondary bacterial infections, caused mainly by Streptococcus pneumoniae, are one of the main complications and responsible for the enhanced morbidity and mortality associated with IAV infections. In spite of the significant advances in our knowledge of IAV infections, holistic comprehension of the interplay between IAV and the host immune response (IR) remains largely fragmented. During the last decade, mathematical modeling has been instrumental to explain and quantify IAV dynamics. In this paper, we review not only the state of the art of mathematical models of IAV infection but also the methodologies exploited for parameter estimation. We focus on the adaptive IR control of IAV infection and the possible mechanisms that could promote a secondary bacterial coinfection. To exemplify IAV dynamics and identifiability issues, a mathematical model to explain the interactions between adaptive IR and IAV infection is considered. Furthermore, in this paper we propose a roadmap for future influenza research. The development of a mathematical modeling framework with a secondary bacterial coinfection, immunosenescence, host genetic factors and responsiveness to vaccination will be pivotal to advance IAV infection understanding and treatment optimization. PMID:26473911

  17. Na Channel β Subunits: Overachievers of the Ion Channel Family.

    PubMed

    Brackenbury, William J; Isom, Lori L

    2011-01-01

    Voltage-gated Na(+) channels (VGSCs) in mammals contain a pore-forming α subunit and one or more β subunits. There are five mammalian β subunits in total: β1, β1B, β2, β3, and β4, encoded by four genes: SCN1B-SCN4B. With the exception of the SCN1B splice variant, β1B, the β subunits are type I topology transmembrane proteins. In contrast, β1B lacks a transmembrane domain and is a secreted protein. A growing body of work shows that VGSC β subunits are multifunctional. While they do not form the ion channel pore, β subunits alter gating, voltage-dependence, and kinetics of VGSCα subunits and thus regulate cellular excitability in vivo. In addition to their roles in channel modulation, β subunits are members of the immunoglobulin superfamily of cell adhesion molecules and regulate cell adhesion and migration. β subunits are also substrates for sequential proteolytic cleavage by secretases. An example of the multifunctional nature of β subunits is β1, encoded by SCN1B, that plays a critical role in neuronal migration and pathfinding during brain development, and whose function is dependent on Na(+) current and γ-secretase activity. Functional deletion of SCN1B results in Dravet Syndrome, a severe and intractable pediatric epileptic encephalopathy. β subunits are emerging as key players in a wide variety of physiopathologies, including epilepsy, cardiac arrhythmia, multiple sclerosis, Huntington's disease, neuropsychiatric disorders, neuropathic and inflammatory pain, and cancer. β subunits mediate multiple signaling pathways on different timescales, regulating electrical excitability, adhesion, migration, pathfinding, and transcription. Importantly, some β subunit functions may operate independently of α subunits. Thus, β subunits perform critical roles during development and disease. As such, they may prove useful in disease diagnosis and therapy. PMID:22007171

  18. An update on avian influenza in Mexico.

    PubMed

    Villarreal-Chávez, C; Rivera-Cruz, E

    2003-01-01

    The avian influenza high-pathogenicity virus was eradicated in poultry of Mexico in a relatively short period by the use of inactivated emulsified vaccine, enforcing biosecurity, and controlling movement of poultry and poultry products. Mexico maintains a permanent and reliable monitoring program for AI. H5N2 is the only avian influenza subtype identified. It is possible to control and eradicate the avian influenza low-pathogenicity virus mainly by controlled depopulation of positive poultry, reinforcing biosecurity, and the use of vaccines. PMID:14575101

  19. Avian influenza surveillance of wild birds

    USGS Publications Warehouse

    Slota, Paul

    2007-01-01

    The President's National Strategy for Pandemic Influenza directs federal agencies to expand the surveillance of United States domestic livestock and wildlife to ensure early warning of hightly pathogenic avian influenza (HPAI) in the U.S. The immediate concern is a potential introduction of HPAI H5N1 virus into the U.S. The presidential directive resulted in the U.S. Interagency Strategic Plan for Early Detection of H5N1 Highly Pathogenic Avian Influenza in Wild Migratory Birds (referred to as the Wild Bird Surveillance Plan or the Plan).

  20. Influenza virus activation of the interferon system

    PubMed Central

    Killip, Marian J.; Fodor, Ervin; Randall, Richard E.

    2015-01-01

    The host interferon (IFN) response represents one of the first barriers that influenza viruses must surmount in order to establish an infection. Many advances have been made in recent years in understanding the interactions between influenza viruses and the interferon system. In this review, we summarise recent work regarding activation of the type I IFN response by influenza viruses, including attempts to identify the viral RNA responsible for IFN induction, the stage of the virus life cycle at which it is generated and the role of defective viruses in this process. PMID:25678267

  1. Evaluation of Alere i Influenza A&B for rapid detection of influenza viruses A and B.

    PubMed

    Nie, Shuping; Roth, Richard B; Stiles, Jeffrey; Mikhlina, Albina; Lu, Xuedong; Tang, Yi-Wei; Babady, N Esther

    2014-09-01

    Rapid and accurate diagnosis of influenza is important for infection control, as well as for patient management. Alere i Influenza A&B is an isothermal nucleic acid amplification-based integrated system for detection and differentiation of influenza virus A and influenza virus B. The performance of the Alere i Influenza A&B was screened using frozen nasopharyngeal-swab specimens collected in viral transport medium (VTM) that were originally tested fresh with the FilmArray Respiratory Panel (RP) assay during the 2012-2013 influenza outbreak. In total, 360 VTM specimens were selected for Alere i Influenza A&B testing: 40 influenza virus A H1N1-2009 (influenza virus A-1), 40 influenza virus A H3N2 (influenza virus A-3), 37 influenza virus A "equivocal" or "no subtype detected" (influenza virus A-u), 41 influenza virus B, and 202 influenza virus-negative specimens, as initially determined by the FilmArray RP assay. The Alere assay showed sensitivities of 87.2%, 92.5%, 25.0%, and 97.4% for influenza virus A-1, influenza virus A-3, influenza virus A-u, and influenza virus B, respectively, after discordant resolution by Prodesse ProFLU+ PCR. The specificities were 100% for both influenza virus A and influenza virus B. In general, the Alere i Influenza A&B provided good sensitivity, although the assay did show poorer sensitivity with samples determined to have low influenza virus A titers by Prodesse ProFlu+ PCR (a mean real-time PCR threshold cycle [CT] value of 31.9 ± 2.0), which included the majority of the samples called influenza virus A "equivocal" or "no subtype detected" by a single BioFire FilmArray RP test. The integrated, rapid, and simple characteristics of the Alere i Influenza A&B assay make it a potential candidate for point-of-care testing, with a test turnaround time of less than 15 min. PMID:24989611

  2. How subunit coupling produces the γ-subunit rotary motion in F1-ATPase

    PubMed Central

    Pu, Jingzhi; Karplus, Martin

    2008-01-01

    FoF1-ATP synthase manufactures the energy “currency,” ATP, of living cells. The soluble F1 portion, called F1-ATPase, can act as a rotary motor, with ATP binding, hydrolysis, and product release, inducing a torque on the γ-subunit. A coarse-grained plastic network model is used to show at a residue level of detail how the conformational changes of the catalytic β-subunits act on the γ-subunit through repulsive van der Waals interactions to generate a torque that drives unidirectional rotation, as observed experimentally. The simulations suggest that the calculated 85° substep rotation is driven primarily by ATP binding and that the subsequent 35° substep rotation is produced by product release from one β-subunit and a concomitant binding pocket expansion of another β-subunit. The results of the simulation agree with single-molecule experiments [see, for example, Adachi K, et al. (2007) Cell 130:309–321] and support a tri-site rotary mechanism for F1-ATPase under physiological condition. PMID:18216260

  3. Studies on chromatin. II. Isolation and characterization of chromatin subunits.

    PubMed Central

    Bakayev, V V; Melnickov, A A; Osicka, V D; Varshausky, A J

    1975-01-01

    Earlier findings /1-10/ bearing on a subunit organization of chromatin were confirmed and in some points detailed. Besides this, a large-scale isolation of chromatin subunits; their protein composition, electron microscopic appearance and CsCl banding pattern are described. Although the purified chromatin subunit contains all five histones, the relative content of histone H1 i in it is two times lower than that in the original chromatin. tit is shown that a mild digestion of chromatin with staphylococcal nuclease produced not only separate chromatin subunits and their "oligomers' but also deoxyribonucleoprotein particles which sediment more slowly than subunits. It appears that these particles and subunits are produced from different initial structures in the chromatin. Finally, a crystallization of the purified chromatin subunit as a cetyltrimethyl ammonium salt is described. Images PMID:1178523

  4. Swine influenza virus: zoonotic potential and vaccination strategies for the control of avian and swine influenzas.

    PubMed

    Thacker, Eileen; Janke, Bruce

    2008-02-15

    Influenza viruses are able to infect humans, swine, and avian species, and swine have long been considered a potential source of new influenza viruses that can infect humans. Swine have receptors to which both avian and mammalian influenza viruses bind, which increases the potential for viruses to exchange genetic sequences and produce new reassortant viruses in swine. A number of genetically diverse viruses are circulating in swine herds throughout the world and are a major cause of concern to the swine industry. Control of swine influenza is primarily through the vaccination of sows, to protect young pigs through maternally derived antibodies. However, influenza viruses continue to circulate in pigs after the decay of maternal antibodies, providing a continuing source of virus on a herd basis. Measures to control avian influenza in commercial poultry operations are dictated by the virulence of the virus. Detection of a highly pathogenic avian influenza (HPAI) virus results in immediate elimination of the flock. Low-pathogenic avian influenza viruses are controlled through vaccination, which is done primarily in turkey flocks. Maintenance of the current HPAI virus-free status of poultry in the United States is through constant surveillance of poultry flocks. Although current influenza vaccines for poultry and swine are inactivated and adjuvanted, ongoing research into the development of newer vaccines, such as DNA, live-virus, or vectored vaccines, is being done. Control of influenza virus infection in poultry and swine is critical to the reduction of potential cross-species adaptation and spread of influenza viruses, which will minimize the risk of animals being the source of the next pandemic. PMID:18269323

  5. Inherent conformational flexibility of F1-ATPase α-subunit.

    PubMed

    Hahn-Herrera, Otto; Salcedo, Guillermo; Barril, Xavier; García-Hernández, Enrique

    2016-09-01

    The core of F1-ATPase consists of three catalytic (β) and three noncatalytic (α) subunits, forming a hexameric ring in alternating positions. A wealth of experimental and theoretical data has provided a detailed picture of the complex role played by catalytic subunits. Although major conformational changes have only been seen in β-subunits, it is clear that α-subunits have to respond to these changes in order to be able to transmit information during the rotary mechanism. However, the conformational behavior of α-subunits has not been explored in detail. Here, we have combined unbiased molecular dynamics (MD) simulations and calorimetrically measured thermodynamic signatures to investigate the conformational flexibility of isolated α-subunits, as a step toward deepening our understanding of its function inside the α3β3 ring. The simulations indicate that the open-to-closed conformational transition of the α-subunit is essentially barrierless, which is ideal to accompany and transmit the movement of the catalytic subunits. Calorimetric measurements of the recombinant α-subunit from Geobacillus kaustophilus indicate that the isolated subunit undergoes no significant conformational changes upon nucleotide binding. Simulations confirm that the nucleotide-free and nucleotide-bound subunits show average conformations similar to that observed in the F1 crystal structure, but they reveal an increased conformational flexibility of the isolated α-subunit upon MgATP binding, which might explain the evolutionary conserved capacity of α-subunits to recognize nucleotides with considerable strength. Furthermore, we elucidate the different dependencies that α- and β-subunits show on Mg(II) for recognizing ATP. PMID:27137408

  6. Cytokine induced changes in proteasome subunit composition are concentration dependent.

    PubMed

    Stohwasser, R; Kloetzel, P M

    1996-09-01

    In eukaryotes, 20S proteasome subunit composition is controlled by the cytokine interferon-gamma (IFN-gamma). IFN-gamma induces the synthesis of the beta-subunits LMP2, LMP7 and MECL-1, which in consequence replace their constitutive subunit homologs delta, MB1 and MC14/Z in the 20S complex. By pulse labeling mouse RMA cells and immunoprecipitation of proteasome complexes with the antibody MP3, we have analysed the effect of different IFN-gamma concentrations on proteasomal subunit composition. Our experiments show that IFN-gamma concentrations as low as 5 U/ml induce subunit substitutions and that overall proteasomal subunit composition is dependent on the cytokine concentration used. An IFN-gamma concentration of 50 U/ml is sufficient for complete replacement of subunit delta by LMP2. In contrast, IFN-gamma treatment never induces a complete replacement of subunit MC14 by MECL-1. These subunits are present at an approximate 1:1 molar ratio, suggesting that both subunits coexist in the same 20S proteasome complex. Furthermore, different regulatory mechanisms have to be postulated for the synthesis and incorporation of the three IFN-gamma inducible proteasome subunits. Both IFN-gamma as well as IL-2 also seem to influence the modification state of the alpha subunit C8. Since the subunit composition is dependent on the cytokine concentration used and strongly influences the proteolytic properties of the 20S proteasome complex, our experiments represent a caveat for experiments in which IFN-gamma dependent proteasomal enzyme characteristics have been analysed without monitoring the subunit composition. PMID:9067255

  7. Cloning and characterization of GABAA α subunits and GABAB subunits in Xenopus laevis during development

    PubMed Central

    Kaeser, Gwendolyn E.; Rabe, Brian A.; Saha, Margaret S.

    2011-01-01

    Gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the adult nervous system, acts via two classes of receptors, the ionotropic GABAA and metabotropic GABAB receptors. During the development of the nervous system GABA acts in a depolarizing, excitatory manner and plays an important role in various neural developmental processes including cell proliferation, migration, synapse formation and activity-dependent differentiation. Here we describe the spatial and temporal expression patterns of the GABAA and GABAB receptors during early development of Xenopus laevis. Using in situ hybridization and qRT-PCR, GABAA α2 was detected as a maternal mRNA. All other α-subunits were first detected by tailbud through hatching stages. Expression of the various subunits was seen in the brain, spinal cord, cranial ganglia, olfactory epithelium, pineal, and pituitary gland. Each receptor subunit showed a distinctive, unique expression pattern suggesting these receptors have specific functions and are regulated in a precise spatial and temporal manner. PMID:21384470

  8. PKA catalytic subunit mutations in adrenocortical Cushing's adenoma impair association with the regulatory subunit.

    PubMed

    Calebiro, Davide; Hannawacker, Annette; Lyga, Sandra; Bathon, Kerstin; Zabel, Ulrike; Ronchi, Cristina; Beuschlein, Felix; Reincke, Martin; Lorenz, Kristina; Allolio, Bruno; Kisker, Caroline; Fassnacht, Martin; Lohse, Martin J

    2014-01-01

    We recently identified a high prevalence of mutations affecting the catalytic (Cα) subunit of protein kinase A (PKA) in cortisol-secreting adrenocortical adenomas. The two identified mutations (Leu206Arg and Leu199_Cys200insTrp) are associated with increased PKA catalytic activity, but the underlying mechanisms are highly controversial. Here we utilize a combination of biochemical and optical assays, including fluorescence resonance energy transfer in living cells, to analyze the consequences of the two mutations with respect to the formation of the PKA holoenzyme and its regulation by cAMP. Our results indicate that neither mutant can form a stable PKA complex, due to the location of the mutations at the interface between the catalytic and the regulatory subunits. We conclude that the two mutations cause high basal catalytic activity and lack of regulation by cAMP through interference of complex formation between the regulatory and the catalytic subunits of PKA. PMID:25477193

  9. Pandemic and Seasonal Influenza: Therapeutic Challenges

    PubMed Central

    Memoli, Matthew J.; Morens, David M.; Taubenberger, Jeffery K.

    2008-01-01

    Influenza A viruses cause significant morbidity and mortality annually, and the threat of a pandemic underscores the need for new therapeutic strategies. Here we briefly discuss novel antiviral agents under investigation, the limitations of current antiviral therapy and stress the importance of secondary bacterial infections in seasonal and pandemic influenza. Additionally, the lack of new antibiotics available to treat increasingly drug resistant organisms such as methicillin-resistant Staphylococcus aureus, pneumococci, Acinetobacter, extended spectrum beta-lactamase producing gram negative bacteria and Clostridium difficile is highlighted as an important component of influenza treatment and pandemic preparedness. Addressing these problems will require a multidisciplinary approach, which includes the development of novel antivirals and new antibiotics, as well as a better understanding of the role secondary infections play on the morbidity and mortality due to influenza infection. PMID:18598914

  10. Broadly neutralizing antibodies against influenza viruses

    PubMed Central

    Laursen, Nick S.; Wilson, Ian A.

    2014-01-01

    Despite available antivirals and vaccines, influenza infections continue to be a major cause of mortality worldwide. Vaccination generally induces an effective, but strain-specific antibody response. As the virus continually evolves, new vaccines have to be administered almost annually when a novel strain becomes dominant. Furthermore, the sporadic emerging resistance to neuraminidase inhibitors among circulating strains suggests an urgent need for new therapeutic agents. Recently, several cross-reactive antibodies have been described, which neutralize an unprecedented spectrum of influenza viruses. These broadly neutralizing antibodies generally target conserved functional regions on the major influenza surface glycoprotein hemagglutinin (HA). The characterization of their neutralization breadth and epitopes on HA could stimulate the development of new antibody-based antivirals and broader influenza vaccines. PMID:23583287

  11. Host genetic determinants of influenza pathogenicity

    PubMed Central

    Lin, Tsai-Yu; Brass, Abraham L.

    2014-01-01

    Despite effective vaccines, influenza remains a major global health threat due to the morbidity and mortality caused by seasonal epidemics, as well as the 2009 pandemic. Also of profound concern are the rare but potentially catastrophic transmissions of avian influenza to humans, highlighted by a recent H7N9 influenza outbreak. Murine and human studies reveal that the clinical course of influenza is the result of a combination of both host and viral genetic determinants. While viral pathogenicity has long been the subject of intensive efforts, research to elucidate host genetic determinants, particularly human, is now in the ascendant, and the goal of this review is to highlight these recent insights. PMID:23933004

  12. Influenza and parainfluenza viral infections in children.

    PubMed

    Fox, Thomas G; Christenson, John C

    2014-06-01

    • On the basis of strong epidemiologic evidence, influenza and parainfluenza viruses are responsible for significant morbidity and mortality in young infants and children and in persons with chronic medical conditions. (1)(4)(26)(27)(35). • On the basis of research evidence, influenza vaccines are effective in preventing disease in high-risk individuals. (8)(17)(18). • On the basis of strong research evidence, influenza vaccines are safe in young infants and children 6 months or older. (8)(15).• On the basis of research evidence, the use of corticosteroids and epinephrine is beneficial in the treatment of laryngotracheitis caused by parainfluenza viruses. (44)(45)(46)(47). • Strong evidence supports the use of influenza vaccines in pregnant mothers as a strategy to prevent disease in infants younger than 6 months. (17)(18)(19). PMID:24891595

  13. State Plans for Containment of Pandemic Influenza

    PubMed Central

    Layton, Christine M.; Ghneim, George S.; Wagener, Diane K.

    2006-01-01

    This review assesses differences and similarities of the states in planning for pandemic influenza. We reviewed the recently posted plans of 49 states for vaccination, early epidemic surveillance and detection, and intraepidemic plans for containment of pandemic influenza. All states generally follow vaccination priorities set by the Advisory Committee on Immunization Practices. They all also depend on National Sentinel Physician Surveillance and other passive surveillance systems to alert them to incipient epidemic influenza, but these systems may not detect local epidemics until they are well established. Because of a lack of epidemiologic data, few states explicitly discuss implementing nonpharmaceutical community interventions: voluntary self-isolation (17 states [35%]), school or other institutional closing (18 [37%]), institutional or household quarantine (15 [31%]), or contact vaccination or chemoprophylaxis (12 [25%]). This review indicates the need for central planning for pandemic influenza and for epidemiologic studies regarding containment strategies in the community. PMID:17073091

  14. Selecting Viruses for the Seasonal Influenza Vaccine

    MedlinePlus

    ... which viruses are selected for use in vaccine production? The influenza viruses in the seasonal flu vaccine ... to get a good vaccine virus for vaccine production? There are a number of factors that can ...

  15. Socioeconomic Disparities and Influenza Hospitalizations, Tennessee, USA

    PubMed Central

    Sloan, Chantel; Chandrasekhar, Rameela; Mitchel, Edward; Schaffner, William

    2015-01-01

    We examined population-based surveillance data from the Tennessee Emerging Infections Program to determine whether neighborhood socioeconomic status was associated with influenza hospitalization rates. Hospitalization data collected during October 2007–April 2014 were geocoded (N = 1,743) and linked to neighborhood socioeconomic data. We calculated age-standardized annual incidence rates, relative index of inequality, and concentration curves for socioeconomic variables. Influenza hospitalizations increased with increased percentages of persons who lived in poverty, had female-headed households, lived in crowded households, and lived in population-dense areas. Influenza hospitalizations decreased with increased percentages of persons who were college educated, were employed, and had health insurance. Higher incidence of influenza hospitalization was also associated with lower neighborhood socioeconomic status when data were stratified by race. PMID:26292106

  16. Targeted social distancing design for pandemic influenza.

    PubMed

    Glass, Robert J; Glass, Laura M; Beyeler, Walter E; Min, H Jason

    2006-11-01

    Targeted social distancing to mitigate pandemic influenza can be designed through simulation of influenza's spread within local community social contact networks. We demonstrate this design for a stylized community representative of a small town in the United States. The critical importance of children and teenagers in transmission of influenza is first identified and targeted. For influenza as infectious as 1957-58 Asian flu (=50% infected), closing schools and keeping children and teenagers at home reduced the attack rate by >90%. For more infectious strains, or transmission that is less focused on the young, adults and the work environment must also be targeted. Tailored to specific communities across the world, such design would yield local defenses against a highly virulent strain in the absence of vaccine and antiviral drugs. PMID:17283616

  17. Targeted Social Distancing Designs for Pandemic Influenza

    PubMed Central

    Glass, Laura M.; Beyeler, Walter E.; Min, H. Jason

    2006-01-01

    Targeted social distancing to mitigate pandemic influenza can be designed through simulation of influenza's spread within local community social contact networks. We demonstrate this design for a stylized community representative of a small town in the United States. The critical importance of children and teenagers in transmission of influenza is first identified and targeted. For influenza as infectious as 1957–58 Asian flu (≈50% infected), closing schools and keeping children and teenagers at home reduced the attack rate by >90%. For more infectious strains, or transmission that is less focused on the young, adults and the work environment must also be targeted. Tailored to specific communities across the world, such design would yield local defenses against a highly virulent strain in the absence of vaccine and antiviral drugs. PMID:17283616

  18. Socioeconomic Disparities and Influenza Hospitalizations, Tennessee, USA.

    PubMed

    Sloan, Chantel; Chandrasekhar, Rameela; Mitchel, Edward; Schaffner, William; Lindegren, Mary Lou

    2015-09-01

    We examined population-based surveillance data from the Tennessee Emerging Infections Program to determine whether neighborhood socioeconomic status was associated with influenza hospitalization rates. Hospitalization data collected during October 2007-April 2014 were geocoded (N = 1,743) and linked to neighborhood socioeconomic data. We calculated age-standardized annual incidence rates, relative index of inequality, and concentration curves for socioeconomic variables. Influenza hospitalizations increased with increased percentages of persons who lived in poverty, had female-headed households, lived in crowded households, and lived in population-dense areas. Influenza hospitalizations decreased with increased percentages of persons who were college educated, were employed, and had health insurance. Higher incidence of influenza hospitalization was also associated with lower neighborhood socioeconomic status when data were stratified by race. PMID:26292106

  19. Neutralization enzyme immunoassay for influenza virus.

    PubMed Central

    Benne, C A; Harmsen, M; De Jong, J C; Kraaijeveld, C A

    1994-01-01

    A neutralization enzyme immunoassay (N-EIA) was developed for the detection of antibody titer rises in sera of patients infected with influenza A (H3N2) virus. In this N-EIA, a selected strain of influenza A (H3N2) virus was added to monolayers of LLC-MK2 cells in microtiter plates. After 24 h, the replicated virus could be demonstrated with a virus-specific enzyme-labeled monoclonal antibody. Preincubation of the influenza virus with convalescent-phase sera of patients infected with influenza A (H3N2) virus resulted 1 day later in decreased absorbance values that could be used for calculation of neutralization titers. From use of paired serum samples from 10 patients with a history of flu-like symptoms, the results obtained with N-EIA correlated well (r = 0.83) with those of the standard hemagglutination inhibition test. PMID:8027355

  20. Epidemiological and Virological Characterization of Influenza B Virus Infections.

    PubMed

    Sharabi, Sivan; Drori, Yaron; Micheli, Michal; Friedman, Nehemya; Orzitzer, Sara; Bassal, Ravit; Glatman-Freedman, Aharona; Shohat, Tamar; Mendelson, Ella; Hindiyeh, Musa; Mandelboim, Michal

    2016-01-01

    While influenza A viruses comprise a heterogeneous group of clinically relevant influenza viruses, influenza B viruses form a more homogeneous cluster, divided mainly into two lineages: Victoria and Yamagata. This divergence has complicated seasonal influenza vaccine design, which traditionally contained two seasonal influenza A virus strains and one influenza B virus strain. We examined the distribution of the two influenza B virus lineages in Israel, between 2011-2014, in hospitalized and in non-hospitalized (community) influenza B virus-infected patients. We showed that influenza B virus infections can lead to hospitalization and demonstrated that during some winter seasons, both influenza B virus lineages circulated simultaneously in Israel. We further show that the influenza B virus Yamagata lineage was dominant, circulating in the county in the last few years of the study period, consistent with the anti-Yamagata influenza B virus antibodies detected in the serum samples of affected individuals residing in Israel in the year 2014. Interestingly, we found that elderly people were particularly vulnerable to Yamagata lineage influenza B virus infections. PMID:27533045

  1. Epidemiological and Virological Characterization of Influenza B Virus Infections

    PubMed Central

    Sharabi, Sivan; Drori, Yaron; Micheli, Michal; Friedman, Nehemya; Orzitzer, Sara; Bassal, Ravit; Glatman-Freedman, Aharona; Shohat, Tamar; Mendelson, Ella; Hindiyeh, Musa; Mandelboim, Michal

    2016-01-01

    While influenza A viruses comprise a heterogeneous group of clinically relevant influenza viruses, influenza B viruses form a more homogeneous cluster, divided mainly into two lineages: Victoria and Yamagata. This divergence has complicated seasonal influenza vaccine design, which traditionally contained two seasonal influenza A virus strains and one influenza B virus strain. We examined the distribution of the two influenza B virus lineages in Israel, between 2011–2014, in hospitalized and in non-hospitalized (community) influenza B virus-infected patients. We showed that influenza B virus infections can lead to hospitalization and demonstrated that during some winter seasons, both influenza B virus lineages circulated simultaneously in Israel. We further show that the influenza B virus Yamagata lineage was dominant, circulating in the county in the last few years of the study period, consistent with the anti-Yamagata influenza B virus antibodies detected in the serum samples of affected individuals residing in Israel in the year 2014. Interestingly, we found that elderly people were particularly vulnerable to Yamagata lineage influenza B virus infections. PMID:27533045

  2. Avian influenza: an emerging pandemic threat.

    PubMed

    Jin, Xian Wen; Mossad, Sherif B

    2005-12-01

    While we are facing the threat of an emerging pandemic from the current avian flu outbreak in Asia, we have learned important traits of the virus responsible for the 1918 Spanish influenza pandemic that made it so deadly. By using stockpiled antiviral drugs effectively and developing an effective vaccine, we can be in a better position than ever to mitigate the global impact of an avian influenza pandemic. PMID:16392727

  3. Broadening Horizons: New Antibodies Against Influenza.

    PubMed

    Jackson, Katherine J L; Boyd, Scott D

    2016-07-28

    Seasonal influenza vaccine formulation efforts struggle to keep up with viral antigenic variation. Two studies now report engineered or naturally occurring human antibodies targeting the influenza hemagglutinin (HA) stem, with exceptional neutralizing breadth (Joyce et al., 2016; Kallewaard et al., 2016). Antibodies with similar structural features are elicited in multiple subjects, suggesting that modified vaccine regimens could provide broad protection. PMID:27471961

  4. Influenza Forecasting with Google Flu Trends

    PubMed Central

    Dugas, Andrea Freyer; Jalalpour, Mehdi; Gel, Yulia; Levin, Scott; Torcaso, Fred; Igusa, Takeru; Rothman, Richard E.

    2013-01-01

    Background We developed a practical influenza forecast model based on real-time, geographically focused, and easy to access data, designed to provide individual medical centers with advanced warning of the expected number of influenza cases, thus allowing for sufficient time to implement interventions. Secondly, we evaluated the effects of incorporating a real-time influenza surveillance system, Google Flu Trends, and meteorological and temporal information on forecast accuracy. Methods Forecast models designed to predict one week in advance were developed from weekly counts of confirmed influenza cases over seven seasons (2004–2011) divided into seven training and out-of-sample verification sets. Forecasting procedures using classical Box-Jenkins, generalized linear models (GLM), and generalized linear autoregressive moving average (GARMA) methods were employed to develop the final model and assess the relative contribution of external variables such as, Google Flu Trends, meteorological data, and temporal information. Results A GARMA(3,0) forecast model with Negative Binomial distribution integrating Google Flu Trends information provided the most accurate influenza case predictions. The model, on the average, predicts weekly influenza cases during 7 out-of-sample outbreaks within 7 cases for 83% of estimates. Google Flu Trend data was the only source of external information to provide statistically significant forecast improvements over the base model in four of the seven out-of-sample verification sets. Overall, the p-value of adding this external information to the model is 0.0005. The other exogenous variables did not yield a statistically significant improvement in any of the verification sets. Conclusions Integer-valued autoregression of influenza cases provides a strong base forecast model, which is enhanced by the addition of Google Flu Trends confirming the predictive capabilities of search query based syndromic surveillance. This accessible and

  5. Vaccines for seasonal and pandemic influenza.

    PubMed

    Nichol, Kristin L; Treanor, John J

    2006-11-01

    Seasonal influenza continues to have a huge annual impact in the United States, accounting for tens of millions of illnesses, hundreds of thousands of excess hospitalizations, and tens of thousands of excess deaths. Vaccination remains the mainstay for the prevention of influenza. In the United States, 2 types of influenza vaccine are currently licensed: trivalent inactivated influenza vaccine and live attenuated influenza vaccine. Both are safe and effective in the populations for which they are approved for use. Children, adults <65 years of age, and the elderly all receive substantial health benefits from vaccination. In addition, vaccination appears to be cost-effective, if not cost saving, across the age spectrum. Despite long-standing recommendations for the routine vaccination of persons in high-priority groups, US vaccination rates remain too low across all age groups. Important issues to be addressed include improving vaccine delivery to current and expanded target groups, ensuring timely availability of adequate vaccine supply, and development of even more effective vaccines. Development of a vaccine against potentially pandemic strains is an essential part of the strategy to control and prevent a pandemic outbreak. The use of existing technologies for influenza vaccine production would be the most straightforward approach, because these technologies are commercially available and licensing would be relatively simple. Approaches currently being tested include subvirion inactivated vaccines and cold-adapted, live attenuated vaccines. Preliminary results have suggested that, for some pandemic antigens, particularly H5, subvirion inactivated vaccines are poorly immunogenic, for reasons that are not clear. Data from evaluation of live pandemic vaccines are pending. Second-generation approaches designed to provide improved immune responses at lower doses have focused on adjuvants such as alum and MF59, which are currently licensed for influenza or other

  6. Order and disorder control the functional rearrangement of influenza hemagglutinin.

    PubMed

    Lin, Xingcheng; Eddy, Nathanial R; Noel, Jeffrey K; Whitford, Paul C; Wang, Qinghua; Ma, Jianpeng; Onuchic, José N

    2014-08-19

    Influenza hemagglutinin (HA), a homotrimeric glycoprotein crucial for membrane fusion, undergoes a large-scale structural rearrangement during viral invasion. X-ray crystallography has shown that the pre- and postfusion configurations of HA2, the membrane-fusion subunit of HA, have disparate secondary, tertiary, and quaternary structures, where some regions are displaced by more than 100 Å. To explore structural dynamics during the conformational transition, we studied simulations of a minimally frustrated model based on energy landscape theory. The model combines structural information from both the pre- and postfusion crystallographic configurations of HA2. Rather than a downhill drive toward formation of the central coiled-coil, we discovered an order-disorder transition early in the conformational change as the mechanism for the release of the fusion peptides from their burial sites in the prefusion crystal structure. This disorder quickly leads to a metastable intermediate with a broken threefold symmetry. Finally, kinetic competition between the formation of the extended coiled-coil and C-terminal melting results in two routes from this intermediate to the postfusion structure. Our study reiterates the roles that cracking and disorder can play in functional molecular motions, in contrast to the downhill mechanical interpretations of the "spring-loaded" model proposed for the HA2 conformational transition. PMID:25082896

  7. The receptor preference of influenza viruses

    PubMed Central

    Meng, Bo; Marriott, Anthony C.; Dimmock, Nigel J.

    2010-01-01

    Please cite this paper as: Meng et al. (2010) The receptor preference of influenza viruses. Influenza and Other Respiratory Viruses 4(3), 147–153. Objectives  The cell surface receptor used by an influenza virus to infect that cell is an N‐acetyl neuraminic acid (NANA) residue terminally linked by an alpha2,3 or alpha2,6 bond to a carbohydrate moiety of a glycoprotein or glycolipid. Our aim was to determine a quick and technically simple method to determine cell receptor usage by whole influenza A virus particles. Methods  We employed surface plasmon resonance to detect the binding of viruses to fetuin, a naturally occurring glycoprotein that has both alpha2,3‐ and alpha2,6‐linked NANA, and free 3′‐sialyllactose or 6′‐sialyllactose to compete virus binding. All virus stocks were produced in embryonated chicken’s eggs. Results  The influenza viruses tested bound preferentially to NANAalpha2,3Gal or to NANAalpha2,6Gal, or showed no preference. Two PR8 viruses had different binding preferences. Binding preferences of viruses correlated well with their known biological properties. Conclusions  Our data suggest that it is not easy to predict receptor usage by influenza viruses. However, direct experimental determination as described here can inform experiments concerned with viral pathogenesis, biology and structure. In principle, the methodology can be used for any virus that binds to a terminal NANA residue. PMID:20409211

  8. Environmental role in influenza virus outbreaks.

    PubMed

    Sooryanarain, Harini; Elankumaran, Subbiah

    2015-01-01

    The environmental drivers of influenza outbreaks are largely unknown. Despite more than 50 years of research, there are conflicting lines of evidence on the role of the environment in influenza A virus (IAV) survival, stability, and transmissibility. With the increasing and looming threat of pandemic influenza, it is important to understand these factors for early intervention and long-term control strategies. The factors that dictate the severity and spread of influenza would include the virus, natural and acquired hosts, virus-host interactions, environmental persistence, virus stability and transmissibility, and anthropogenic interventions. Virus persistence in different environments is subject to minor variations in temperature, humidity, pH, salinity, air pollution, and solar radiations. Seasonality of influenza is largely dictated by temperature and humidity, with cool-dry conditions enhancing IAV survival and transmissibility in temperate climates in high latitudes, whereas humid-rainy conditions favor outbreaks in low latitudes, as seen in tropical and subtropical zones. In mid-latitudes, semiannual outbreaks result from alternating cool-dry and humid-rainy conditions. The mechanism of virus survival in the cool-dry or humid-rainy conditions is largely determined by the presence of salts and proteins in the respiratory droplets. Social determinants of heath, including health equity, vaccine acceptance, and age-related illness, may play a role in influenza occurrence and spread. PMID:25422855

  9. Innate Immune Sensing and Response to Influenza

    PubMed Central

    Pulendran, Bali; Maddur, Mohan S.

    2015-01-01

    Influenza viruses pose a substantial threat to human and animal health worldwide. Recent studies in mouse models have revealed an indispensable role for the innate immune system in defense against influenza virus. Recognition of the virus by innate immune receptors in a multitude of cell types activates intricate signaling networks, functioning to restrict viral replication. Downstream effector mechanisms include activation of innate immune cells and, induction and regulation of adaptive immunity. However, uncontrolled innate responses are associated with exaggerated disease, especially in pandemic influenza virus infection. Despite advances in the understanding of innate response to influenza in the mouse model, there is a large knowledge gap in humans, particularly in immunocom-promised groups such as infants and the elderly. We propose here, the need for further studies in humans to decipher the role of innate immunity to influenza virus, particularly at the site of infection. These studies will complement the existing work in mice and facilitate the quest to design improved vaccines and therapeutic strategies against influenza. PMID:25078919

  10. Integrating influenza antigenic dynamics with molecular evolution

    PubMed Central

    Bedford, Trevor; Suchard, Marc A; Lemey, Philippe; Dudas, Gytis; Gregory, Victoria; Hay, Alan J; McCauley, John W; Russell, Colin A; Smith, Derek J; Rambaut, Andrew

    2014-01-01

    Influenza viruses undergo continual antigenic evolution allowing mutant viruses to evade host immunity acquired to previous virus strains. Antigenic phenotype is often assessed through pairwise measurement of cross-reactivity between influenza strains using the hemagglutination inhibition (HI) assay. Here, we extend previous approaches to antigenic cartography, and simultaneously characterize antigenic and genetic evolution by modeling the diffusion of antigenic phenotype over a shared virus phylogeny. Using HI data from influenza lineages A/H3N2, A/H1N1, B/Victoria and B/Yamagata, we determine patterns of antigenic drift across viral lineages, showing that A/H3N2 evolves faster and in a more punctuated fashion than other influenza lineages. We also show that year-to-year antigenic drift appears to drive incidence patterns within each influenza lineage. This work makes possible substantial future advances in investigating the dynamics of influenza and other antigenically-variable pathogens by providing a model that intimately combines molecular and antigenic evolution. DOI: http://dx.doi.org/10.7554/eLife.01914.001 PMID:24497547

  11. The Global Influenza Initiative recommendations for the vaccination of pregnant women against seasonal influenza.

    PubMed

    Macias, Alejandro E; Precioso, Alexander R; Falsey, Ann R

    2015-08-01

    There is a heavy disease burden due to seasonal influenza in pregnant women, their fetuses, and their newborns. The main aim of this study was to review and analyze current evidence on safety, immunogenicity, and clinical benefits of the inactivated influenza vaccine (IIV) in pregnant women. Current evidence shows that in pregnant women, the seasonal and pandemic IIVs are safe and well tolerated. After vaccination, pregnant women have protective concentrations of anti-influenza antibodies, conferring immunogenicity in newborns. The best evidence, to date, suggests that influenza vaccination confers clinical benefits in both pregnant women and their newborns. Vaccination with either the seasonal or pandemic vaccine has been shown to be cost-effective in pregnancy. There are scarce data from randomized clinical trials; fortunately, new phase 3 clinical trials are under way. In the Northern and Southern Hemispheres, data suggest that the greatest clinical benefit for infants occurs if the IIV is administered within the first weeks of availability of the vaccine, at the beginning of the influenza season, regardless of the pregnancy trimester. The optimal timing to vaccinate pregnant women who live in tropical regions is unclear. Based on evaluation of the evidence, the Global Influenza Initiative (GII) recommends that to prevent seasonal influenza morbidity and mortality in infants and their mothers, all pregnant women, regardless of trimester, should be vaccinated with the IIV. For countries where vaccination against influenza is starting or expanding, the GII recommends that pregnant women have the highest priority. PMID:26256293

  12. Awareness of Influenza and Attitude Toward Influenza Vaccination Among Medical Students.

    PubMed

    Banaszkiewicz, A; Talarek, E; Śliwka, J; Kazubski, F; Małecka, I; Stryczyńska-Kazubska, J; Dziubak, W; Kuchar, E

    2016-01-01

    In Poland, influenza vaccination coverage among both the general population and healthcare workers is low. The aim of the study was to evaluate attitudes towards influenza vaccination among final-year medical students compared with first-year students at medical schools in Poland. Students were asked about the last season's influenza vaccination and what the reasons were for having, or not having, the vaccination. The knowledge of influenza was assessed using a 10-point visual analog scale. The study group consisted of 712 medical students, 404 in the first year and 308 in the final year (35 % and 31 % of all students in those years, respectively). Final-year students believed they had a better knowledge of influenza (OR = 3.33; CI95 %: 2.54-4.39). They answered questions about influenza immunizations (OR = 0.59; CI95 %: 0.44-0.78) and vaccination recommendations in pregnant women correctly more frequently (OR = 0.21; CI95 %: 0.16-0.28). The influenza vaccination rate among students in the 2014/2015 season was similar (17.1 % in the first vs. 15.9 % in the final year, NS). Among the final-year students, the reason for not having the vaccination was mainly financial and not any other. We conclude that although medical students' knowledge about influenza increases in the course of study, it did not much affect their unwilling attitude toward vaccination. PMID:27241508

  13. Seasonal trivalent inactivated influenza vaccine protects against 1918 Spanish influenza virus in ferrets

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The influenza H1N1 pandemic of 1918 was one of the worst medical disasters in human history. Recent studies have demonstrated that the hemagglutinin (HA) protein of the 1918 virus and 2009 H1N1 pandemic virus, the latter now a component of the seasonal trivalent inactivated influenza vaccine (TIV),...

  14. Relationship Between Upper Respiratory Tract Influenza Test Result and Clinical Outcomes Among Critically Ill Influenza Patients

    PubMed Central

    Reddy, Krishna P.; Bajwa, Ednan K.; Parker, Robert A.; Onderdonk, Andrew B.; Walensky, Rochelle P.

    2016-01-01

    Among critically ill patients with lower respiratory tract (LRT)-confirmed influenza, we retrospectively observed worse 28-day clinical outcomes in upper respiratory tract (URT)-negative versus URT-positive subjects. This finding may reflect disease progression and highlights the need for influenza testing of both URT and LRT specimens to improve diagnostic yield and possibly inform prognosis. PMID:26966696

  15. Influenza: the virus and prophylaxis with inactivated influenza vaccine in "at risk" groups, including COPD patients.

    PubMed

    Hovden, Arnt-Ove; Cox, Rebecca Jane; Haaheim, Lars Reinhardt

    2007-01-01

    Influenza is a major respiratory pathogen, which exerts a huge human and economic toll on society. Influenza is a vaccine preventable disease, however, the vaccine strains must be annually updated due to the continuous antigenic changes in the virus. Inactivated influenza vaccines have been used for over 50 years and have an excellent safety record. Annual vaccination is therefore recommended for all individuals with serious medical conditions, like COPD, and protects the vaccinee against influenza illness and also against hospitalization and death. In COPD patients, influenza infection can lead to exacerbations resulting in reduced quality of life, hospitalization and death in the most severe cases. Although there is only limited literature on the use of influenza vaccination solely in COPD patients, there is clearly enough evidence to recommend annual vaccination in this group. This review will focus on influenza virus and prophylaxis with inactivated influenza vaccines in COPD patients and other "at risk" groups to reduce morbidity, save lives, and reduce health care costs. PMID:18229561

  16. The Global Influenza Initiative recommendations for the vaccination of pregnant women against seasonal influenza

    PubMed Central

    Macias, Alejandro E; Precioso, Alexander R; Falsey, Ann R

    2015-01-01

    There is a heavy disease burden due to seasonal influenza in pregnant women, their fetuses, and their newborns. The main aim of this study was to review and analyze current evidence on safety, immunogenicity, and clinical benefits of the inactivated influenza vaccine (IIV) in pregnant women. Current evidence shows that in pregnant women, the seasonal and pandemic IIVs are safe and well tolerated. After vaccination, pregnant women have protective concentrations of anti-influenza antibodies, conferring immunogenicity in newborns. The best evidence, to date, suggests that influenza vaccination confers clinical benefits in both pregnant women and their newborns. Vaccination with either the seasonal or pandemic vaccine has been shown to be cost-effective in pregnancy. There are scarce data from randomized clinical trials; fortunately, new phase 3 clinical trials are under way. In the Northern and Southern Hemispheres, data suggest that the greatest clinical benefit for infants occurs if the IIV is administered within the first weeks of availability of the vaccine, at the beginning of the influenza season, regardless of the pregnancy trimester. The optimal timing to vaccinate pregnant women who live in tropical regions is unclear. Based on evaluation of the evidence, the Global Influenza Initiative (GII) recommends that to prevent seasonal influenza morbidity and mortality in infants and their mothers, all pregnant women, regardless of trimester, should be vaccinated with the IIV. For countries where vaccination against influenza is starting or expanding, the GII recommends that pregnant women have the highest priority. PMID:26256293

  17. Clinical symptoms cannot predict influenza infection during the 2013 influenza season in Bavaria, Germany.

    PubMed

    Campe, H; Heinzinger, S; Hartberger, C; Sing, A

    2016-04-01

    For influenza surveillance and diagnosis typical clinical symptoms are traditionally used to discriminate influenza virus infections from infections by other pathogens. During the 2013 influenza season we performed a multiplex assay for 16 different viruses in 665 swabs from patients with acute respiratory infections (ARIs) to display the variety of different pathogens causing ARI and to test the diagnostic value of both the commonly used case definitions [ARI, and influenza like illness (ILI)] as well as the clinical judgement of physicians, respectively, to achieve a laboratory-confirmed influenza diagnosis. Fourteen different viruses were identified as causing ARI/ILI. Influenza diagnosis based on clinical signs overestimated the number of laboratory-confirmed influenza cases and misclassified cases. Furthermore, ILI case definition and physicians agreed in only 287/651 (44%) cases with laboratory confirmation. Influenza case management has to be supported by laboratory confirmation to allow evidence-based decisions. Epidemiological syndromic surveillance data should be supported by laboratory confirmation for reasonable interpretation. PMID:26388141

  18. The role of weather on the relation between influenza and influenza-like illness.

    PubMed

    van Noort, Sander P; Águas, Ricardo; Ballesteros, Sébastien; Gomes, M Gabriela M

    2012-04-01

    Influenza epidemics, enabled by viral antigenic drift, occur invariably each winter in temperate climates. However, attempts to correlate the magnitude of virus change and epidemic size have been unsatisfactory. The incidence of influenza is not typically measured directly, but rather derived from the incidence of influenza-like illness (ILI), a clinical syndrome. Weather factors have been shown to influence the manifestation of influenza-like symptoms. We fitted an influenza transmission model to time series of influenza-like illness as monitored from 2003 to 2010 by two independent symptomatic surveillance systems (Influenzanet and EISN) in three European countries. By assuming that seasonality only acts upon the manifestation of symptoms, the model shows a significant correlation between the absolute humidity and temperature at the time of infection, and the proportion of influenza infections fulfilling the clinical ILI case definition, the so-called ILI factor. When a weather-dependent ILI factor is included in the model, the epidemic size of influenza-like illness becomes dependent not only on the susceptibility of the population at the beginning of the epidemic season but also on the weather conditions during which the epidemic unfolds. The combination reduces season-to-season variation in epidemic size and, interestingly, leads to a non-monotonic trend whereby the largest ILI epidemic occurs for moderate initial susceptibility. PMID:22214751

  19. Novel Inhibitors of Influenza Virus Fusion: Structure-Activity Relationship and Interaction with the Viral Hemagglutinin▿

    PubMed Central

    Vanderlinden, Evelien; Göktaş, Fusun; Cesur, Zafer; Froeyen, Matheus; Reed, Mark L.; Russell, Charles J.; Cesur, Nesrin; Naesens, Lieve

    2010-01-01

    A new class of N-(1-thia-4-azaspiro[4.5]decan-4-yl)carboxamide inhibitors of influenza virus hemagglutinin (HA)-mediated membrane fusion that has a narrow and defined structure-activity relationship was identified. In Madin-Darby canine kidney (MDCK) cells infected with different strains of human influenza virus A/H3N2, the lead compound, 4c, displayed a 50% effective concentration of 3 to 23 μM and an antiviral selectivity index of 10. No activity was observed for A/H1N1, A/H5N1, A/H7N2, and B viruses. The activity of 4c was reduced considerably when added 30 min or later postinfection, indicating that 4c inhibits an early step in virus replication. 4c and its congeners inhibited influenza A/H3N2 virus-induced erythrocyte hemolysis at low pH. 4c-resistant virus mutants, selected in MDCK cells, contained either a single D112N change in the HA2 subunit of the viral HA or a combination of three substitutions, i.e., R220S (in HA1) and E57K (in HA2) and an A-T substitution at position 43 or 96 of HA2. The mutants showed efficiency for receptor binding and replication similar to that of wild-type virus yet displayed an increased pH of erythrocyte hemolysis. In polykaryon assays with cells expressing single-mutant HA proteins, the E57K, A96T, and D112N mutations resulted in 4c resistance, and the HA proteins containing R220S, A96T, and D112N mutations displayed an increased fusion pH. Molecular modeling identified a binding cavity for 4c involving arginine-54 and glutamic acid-57 in the HA2 subunit. Our studies with the new fusion inhibitor 4c confirm the importance of this HA region in the development of influenza virus fusion inhibitors. PMID:20181685

  20. [Nose surgical anatomy in six aesthetic subunits].

    PubMed

    Chaput, B; Lauwers, F; Lopez, R; Saboye, J; André, A; Grolleau, J-L; Chavoin, J-P

    2013-04-01

    The nose is a complex entity, combining aesthetic and functional roles. Descriptive anatomy is a fundamental science that it can be difficult to relate directly to our daily surgical activity. Reasoning in terms of aesthetic subunits to decide on his actions appeared to us so obvious. The aim of this paper is to resume the anatomical bases relevant to our daily practice in order to fully apprehend the restorative or cosmetic procedures. We discuss the limits of the systematization of these principles in nasal oncology. PMID:22699003

  1. MspA Nanopores from Subunit Dimers

    PubMed Central

    Pavlenok, Mikhail; Derrington, Ian M.; Gundlach, Jens H.; Niederweis, Michael

    2012-01-01

    Mycobacterium smegmatis porin A (MspA) forms an octameric channel and represents the founding member of a new family of pore proteins. Control of subunit stoichiometry is important to tailor MspA for nanotechnological applications. In this study, two MspA monomers were connected by linkers ranging from 17 to 62 amino acids in length. The oligomeric pore proteins were purified from M. smegmatis and were shown to form functional channels in lipid bilayer experiments. These results indicated that the peptide linkers did not prohibit correct folding and localization of MspA. However, expression levels were reduced by 10-fold compared to wild-type MspA. MspA is ideal for nanopore sequencing due to its unique pore geometry and its robustness. To assess the usefulness of MspA made from dimeric subunits for DNA sequencing, we linked two M1-MspA monomers, whose constriction zones were modified to enable DNA translocation. Lipid bilayer experiments demonstrated that this construct also formed functional channels. Voltage gating of MspA pores made from M1 monomers and M1-M1 dimers was identical indicating similar structural and dynamic channel properties. Glucose uptake in M. smegmatis cells lacking porins was restored by expressing the dimeric mspA M1 gene indicating correct folding and localization of M1-M1 pores in their native membrane. Single-stranded DNA hairpins produced identical ionic current blockades in pores made from monomers and subunit dimers demonstrating that M1-M1 pores are suitable for DNA sequencing. This study provides the proof of principle that production of single-chain MspA pores in M. smegmatis is feasible and paves the way for generating MspA pores with altered stoichiometries. Subunit dimers enable better control of the chemical and physical properties of the constriction zone of MspA. This approach will be valuable both in understanding transport across the outer membrane in mycobacteria and in tailoring MspA for nanopore sequencing of DNA. PMID

  2. MspA nanopores from subunit dimers.

    PubMed

    Pavlenok, Mikhail; Derrington, Ian M; Gundlach, Jens H; Niederweis, Michael

    2012-01-01

    Mycobacterium smegmatis porin A (MspA) forms an octameric channel and represents the founding member of a new family of pore proteins. Control of subunit stoichiometry is important to tailor MspA for nanotechnological applications. In this study, two MspA monomers were connected by linkers ranging from 17 to 62 amino acids in length. The oligomeric pore proteins were purified from M. smegmatis and were shown to form functional channels in lipid bilayer experiments. These results indicated that the peptide linkers did not prohibit correct folding and localization of MspA. However, expression levels were reduced by 10-fold compared to wild-type MspA. MspA is ideal for nanopore sequencing due to its unique pore geometry and its robustness. To assess the usefulness of MspA made from dimeric subunits for DNA sequencing, we linked two M1-MspA monomers, whose constriction zones were modified to enable DNA translocation. Lipid bilayer experiments demonstrated that this construct also formed functional channels. Voltage gating of MspA pores made from M1 monomers and M1-M1 dimers was identical indicating similar structural and dynamic channel properties. Glucose uptake in M. smegmatis cells lacking porins was restored by expressing the dimeric mspA M1 gene indicating correct folding and localization of M1-M1 pores in their native membrane. Single-stranded DNA hairpins produced identical ionic current blockades in pores made from monomers and subunit dimers demonstrating that M1-M1 pores are suitable for DNA sequencing. This study provides the proof of principle that production of single-chain MspA pores in M. smegmatis is feasible and paves the way for generating MspA pores with altered stoichiometries. Subunit dimers enable better control of the chemical and physical properties of the constriction zone of MspA. This approach will be valuable both in understanding transport across the outer membrane in mycobacteria and in tailoring MspA for nanopore sequencing of DNA. PMID

  3. U.S. utilization patterns of influenza antiviral medications during the 2009 H1N1 influenza pandemic

    PubMed Central

    Borders‐Hemphill, Vicky; Mosholder, Andrew

    2012-01-01

    Please cite this paper as: Borders‐Hemphill and Mosholder (2012) U.S. utilization patterns of influenza antiviral medications during the 2009 H1N1 influenza pandemic. Influenza and Other Respiratory Viruses 6(601), e129–e133. Background  The 2009 H1N1 influenza pandemic in the United States occurred from April 2009 to April 2010. The 2009 H1N1 influenza virus was susceptible to neuraminidase inhibitors (oseltamivir and zanamivir). Objectives  To characterize the 2009 H1N1 influenza pandemic in the United States from April 2009 to April 2010 using weekly influenza antiviral prescription utilization data and the CDC’s weekly reports of the number of visits for influenza‐like‐illnesses by the Influenza Sentinel Provider Surveillance Network. Methods  A proprietary outpatient data source used by the FDA, which captures adjudicated U.S. prescription claims for select influenza antiviral drugs, was used to conduct this analysis. Data were extracted weekly and analyzed for surveillance during the pandemic. Results were compiled at the end of the pandemic. Results  Oseltamivir has dominated the U.S. influenza antiviral market share of dispensed prescriptions since approval in October 1999 and was the primary influenza antiviral drug used during the 2009 H1N1 influenza pandemic. However, commercial availability of the suspension formulation of oseltamivir was reduced by high demand during the pandemic. Dispensed prescription trends of other influenza antiviral medications studied followed that those of oseltamivir, even antivirals for which the 2009 H1N1 strains showed resistance. Conclusion  Weekly prescription utilization of all influenza antivirals used to treat influenza during the seasonal influenza outbreak followed the same trend of weekly reports of the number of visits for influenza‐like‐illnesses (ILI) by the Influenza Sentinel Provider Surveillance Network. The ILI epidemic curve resembled dispensed antiviral prescription trends (both

  4. Influenza Activity - United States, 2015-16 Season and Composition of the 2016-17 Influenza Vaccine.

    PubMed

    Davlin, Stacy L; Blanton, Lenee; Kniss, Krista; Mustaquim, Desiree; Smith, Sophie; Kramer, Natalie; Cohen, Jessica; Cummings, Charisse Nitura; Garg, Shikha; Flannery, Brendan; Fry, Alicia M; Grohskopf, Lisa A; Bresee, Joseph; Wallis, Teresa; Sessions, Wendy; Garten, Rebecca; Xu, Xiyan; Elal, Anwar Isa Abd; Gubareva, Larisa; Barnes, John; Wentworth, David E; Burns, Erin; Katz, Jacqueline; Jernigan, Daniel; Brammer, Lynnette

    2016-01-01

    During the 2015-16 influenza season (October 4, 2015-May 21, 2016) in the United States, influenza activity* was lower and peaked later compared with the previous three seasons (2012-13, 2013-14, and 2014-15). Activity remained low from October 2015 until late December 2015 and peaked in mid-March 2016. During the most recent 18 influenza seasons (including this season), only two other seasons have peaked in March (2011-12 and 2005-06). Overall influenza activity was moderate this season, with a lower percentage of outpatient visits for influenza-like illness (ILI),(†) lower hospitalization rates, and a lower percentage of deaths attributed to pneumonia and influenza (P&I) compared with the preceding three seasons. Influenza A(H1N1)pdm09 viruses predominated overall, but influenza A(H3N2) viruses were more commonly identified from October to early December, and influenza B viruses were more commonly identified from mid-April through mid-May. The majority of viruses characterized this season were antigenically similar to the reference viruses representing the recommended components of the 2015-16 Northern Hemisphere influenza vaccine (1). This report summarizes influenza activity in the United States during the 2015-16 influenza season (October 4, 2015-May 21, 2016)(§) and reports the vaccine virus components recommended for the 2016-17 Northern Hemisphere influenza vaccines. PMID:27281364

  5. Sialic acid content in human saliva and anti-influenza activity against human and avian influenza viruses.

    PubMed

    Limsuwat, Nattavatchara; Suptawiwat, Ornpreya; Boonarkart, Chompunuch; Puthavathana, Pilaipan; Wiriyarat, Witthawat; Auewarakul, Prasert

    2016-03-01

    It was shown previously that human saliva has higher antiviral activity against human influenza viruses than against H5N1 highly pathogenic avian influenza viruses, and that the major anti-influenza activity was associated with sialic-acid-containing molecules. To further characterize the differential susceptibility to saliva among influenza viruses, seasonal influenza A and B virus, pandemic H1N1 virus, and 15 subtypes of avian influenza virus were tested for their susceptibility to human and chicken saliva. Human saliva showed higher hemagglutination inhibition (HI) and neutralization (NT) titers against seasonal influenza A virus and the pandemic H1N1 viruses than against influenza B virus and most avian influenza viruses, except for H9N2 and H12N9 avian influenza viruses, which showed high HI and NT titers. To understand the nature of sialic-acid-containing anti-influenza factors in human saliva, α2,3- and α2,6-linked sialic acid was measured in human saliva samples using a lectin binding and dot blot assay. α2,6-linked sialic acid was found to be more abundant than α2,3-linked sialic acid, and a seasonal H1N1 influenza virus bound more efficiently to human saliva than an H5N1 virus in a dot blot analysis. These data indicated that human saliva contains the sialic acid type corresponding to the binding preference of seasonal influenza viruses. PMID:26671828

  6. Analysis of the phosphofructokinase subunits and isoenzymes in human tissues.

    PubMed Central

    Dunaway, G A; Kasten, T P; Sebo, T; Trapp, R

    1988-01-01

    The 6-phosphofructo-1-kinase (PFK) subunits and isoenzymes were studied in human muscle, heart, brain, liver, platelets, fibroblasts, erythrocytes, placenta and umbilical cord. In each tissue, the subunit types in the native isoenzymes were characterized by immunological titration with subunit-specific antibodies and by column chromatography on QAE (quaternary aminoethyl)-Sephadex. Further, the subunits of the partially purified native isoenzymes were resolved by SDS/polyacrylamide-gel electrophoresis, identified by immunoblotting, and quantified by scanning gel densitometry of silver-stained gels and immunoblots. Depending on the type of tissue, one to three subunits were detected. The Mr values of the L, M and C subunits regardless of tissue were 76,700 +/- 1400, 82,500 +/- 1640 and 86,500 +/- 1620. Of the tissues studied, only the muscle PFK isoenzymes exhibited one subunit, which was the M-type subunit. Of the other tissues studied, the PFK isoenzymes contained various amounts of all three subunits. Considering the properties of the native PFK isoenzymes, it is clear that, in human tissues, they are not simply various combinations of two or three homotetrameric isoenzymes, but complex mixtures of homotetramers and heterotetramers. The kinetic/regulatory properties of the various isoenzyme pools were found to be dependent on subunit composition. Images Fig. 1. PMID:2970843

  7. Influenza update 2007-2008: vaccine advances, pandemic preparation.

    PubMed

    Mossad, Sherif B

    2007-12-01

    Influenza vaccination remains our best measure to prevent epidemic and pandemic influenza. We must continue to improve vaccination rates for targeted populations. Antiviral options are currently limited to the neuraminidase inhibitors. PMID:18183839

  8. Avian Influenza A (H7N9) Virus

    MedlinePlus

    ... this page: About CDC.gov . Avian Influenza H5 Viruses in the United States Updates and Publications Information ... Humans Examples of Human Infections with Avian Influenza Viruses Outbreaks Health Care and Laboratorian Guidance HPAI A ...

  9. Prevention and Treatment of Avian Influenza A Viruses in People

    MedlinePlus

    ... Research Making a Candidate Vaccine Virus Related Links Influenza Types Seasonal Avian Swine Variant Pandemic Other Get ... Button Past Newsletters Prevention and Treatment of Avian Influenza A Viruses in People Language: English Español ...

  10. Transmission of Avian Influenza A Viruses Between Animals and People

    MedlinePlus

    ... many different animals, including ducks, chickens, pigs, whales, horses, and seals. However, certain subtypes of influenza A ... pigs, and H7N7 and H3N8 virus infections of horses. Influenza A viruses that typically infect and transmit ...

  11. DIESEL EXHAUST ENHANCES INFLUENZA VIRUS INFECTIONS IN RESPIRATORY EPITHELIAL CELLS

    EPA Science Inventory

    Several factors, such as age and nutritional status can affect the susceptibility to influenza infections. Moreover, exposure to air pollutants, such as diesel exhaust (DE), has been shown to affect respiratory virus infections in rodent models. Influenza virus primarily infects ...

  12. Animal models for influenza virus pathogenesis, transmission, and immunology

    PubMed Central

    Thangavel, Rajagowthamee R.; Bouvier, Nicole M.

    2014-01-01

    In humans, infection with an influenza A or B virus manifests typically as an acute and self-limited upper respiratory tract illness characterized by fever, cough, sore throat, and malaise. However, influenza can present along a broad spectrum of disease, ranging from sub-clinical or even asymptomatic infection to a severe primary viral pneumonia requiring advanced medical supportive care. Disease severity depends upon the virulence of the influenza virus strain and the immune competence and previous influenza exposures of the patient. Animal models are used in influenza research not only to elucidate the viral and host factors that affect influenza disease outcomes in and spread among susceptible hosts, but also to evaluate interventions designed to prevent or reduce influenza morbidity and mortality in man. This review will focus on the three animal models currently used most frequently in influenza virus research -- mice, ferrets, and guinea pigs -- and discuss the advantages and disadvantages of each. PMID:24709389

  13. Cross talk between animal and human influenza viruses.

    PubMed

    Ozawa, Makoto; Kawaoka, Yoshihiro

    2013-01-01

    Although outbreaks of highly pathogenic avian influenza in wild and domestic birds have been posing the threat of a new influenza pandemic for the past decade, the first pandemic of the twenty-first century came from swine viruses. This fact emphasizes the complexity of influenza viral ecology and the difficulty of predicting influenza viral dynamics. Complete control of influenza viruses seems impossible. However, we must minimize the impact of animal and human influenza outbreaks by learning lessons from past experiences and recognizing the current status. Here, we review the most recent influenza virology data in the veterinary field, including aspects of zoonotic agents and recent studies that assess the pandemic potential of H5N1 highly pathogenic avian influenza viruses. PMID:25387011

  14. The Burden of Influenza B: A Structured Literature Review

    PubMed Central

    Paul Glezen, W.; Kuehn, Carrie M.; Ryan, Kellie J.; Oxford, John

    2013-01-01

    We reviewed the epidemiology, clinical characteristics, disease severity, and economic burden of influenza B as reported in the peer-reviewed published literature. We used MEDLINE to perform a systematic literature review of peer-reviewed, English-language literature published between 1995 and 2010. Widely variable frequency data were reported. Clinical presentation of influenza B was similar to that of influenza A, although we observed conflicting reports. Influenza B–specific data on hospitalization rates, length of stay, and economic outcomes were limited but demonstrated that the burden of influenza B can be significant. The medical literature demonstrates that influenza B can pose a significant burden to the global population. The comprehensiveness and quality of reporting on influenza B, however, could be substantially improved. Few articles described complications. Additional data regarding the incidence, clinical burden, and economic impact of influenza B would augment our understanding of the disease and assist in vaccine development. PMID:23327249

  15. The Influenza NS1 Protein: What Do We Know in Equine Influenza Virus Pathogenesis?

    PubMed

    Barba, Marta; Daly, Janet M

    2016-01-01

    Equine influenza virus remains a serious health and potential economic problem throughout most parts of the world, despite intensive vaccination programs in some horse populations. The influenza non-structural protein 1 (NS1) has multiple functions involved in the regulation of several cellular and viral processes during influenza infection. We review the strategies that NS1 uses to facilitate virus replication and inhibit antiviral responses in the host, including sequestering of double-stranded RNA, direct modulation of protein kinase R activity and inhibition of transcription and translation of host antiviral response genes such as type I interferon. Details are provided regarding what it is known about NS1 in equine influenza, especially concerning C-terminal truncation. Further research is needed to determine the role of NS1 in equine influenza infection, which will help to understand the pathophysiology of complicated cases related to cytokine imbalance and secondary bacterial infection, and to investigate new therapeutic and vaccination strategies. PMID:27589809

  16. Subunit Arrangement and Function in NMDA Receptors

    SciTech Connect

    Furukawa,H.; Singh, S.; Mancusso, R.; Gouaux, E.

    2005-01-01

    Excitatory neurotransmission mediated by NMDA (N-methyl-D-aspartate) receptors is fundamental to the physiology of the mammalian central nervous system. These receptors are heteromeric ion channels that for activation require binding of glycine and glutamate to the NR1 and NR2 subunits, respectively. NMDA receptor function is characterized by slow channel opening and deactivation, and the resulting influx of cations initiates signal transduction cascades that are crucial to higher functions including learning and memory. Here we report crystal structures of the ligand-binding core of NR2A with glutamate and that of the NR1-NR2A heterodimer with glutamate and glycine. The NR2A-glutamate complex defines the determinants of glutamate and NMDA recognition, and the NR1-NR2A heterodimer suggests a mechanism for ligand-induced ion channel opening. Analysis of the heterodimer interface, together with biochemical and electrophysiological experiments, confirms that the NR1-NR2A heterodimer is the functional unit in tetrameric NMDA receptors and that tyrosine 535 of NR1, located in the subunit interface, modulates the rate of ion channel deactivation.

  17. TSH Receptor Cleavage Into Subunits and Shedding of the A-Subunit; A Molecular and Clinical Perspective.

    PubMed

    Rapoport, Basil; McLachlan, Sandra M

    2016-04-01

    The TSH receptor (TSHR) on the surface of thyrocytes is unique among the glycoprotein hormone receptors in comprising two subunits: an extracellular A-subunit, and a largely transmembrane and cytosolic B-subunit. Unlike its ligand TSH, whose subunits are encoded by two genes, the TSHR is expressed as a single polypeptide that subsequently undergoes intramolecular cleavage into disulfide-linked subunits. Cleavage is associated with removal of a C-peptide region, a mechanism similar in some respects to insulin cleavage into disulfide linked A- and B-subunits with loss of a C-peptide region. The potential pathophysiological importance of TSHR cleavage into A- and B-subunits is that some A-subunits are shed from the cell surface. Considerable experimental evidence supports the concept that A-subunit shedding in genetically susceptible individuals is a factor contributing to the induction and/or affinity maturation of pathogenic thyroid-stimulating autoantibodies, the direct cause of Graves' disease. The noncleaving gonadotropin receptors are not associated with autoantibodies that induce a "Graves' disease of the gonads." We also review herein current information on the location of the cleavage sites, the enzyme(s) responsible for cleavage, the mechanism by which A-subunits are shed, and the effects of cleavage on receptor signaling. PMID:26799472

  18. Personalized medicine in severe influenza.

    PubMed

    Valenzuela-Sánchez, F; Valenzuela-Méndez, B; Rodríguez-Gutiérrez, J F; Rello, J

    2016-06-01

    Existing therapies against infectious diseases may only be effective in limited subpopulations during specific phases of diseases, incorporating theranostics, and there is a clear need to individualize different therapeutic approaches depending on the host. Influenza A virus infection evolves into a severe respiratory failure in some young adult patients, related to an exaggerated inflammatory response. Mortality rates remain high despite antiviral treatment and aggressive respiratory support. The influenza A virus (IAV) infection will induce a proinflammatory innate immune response through recognition of viral RNA by Toll-like receptor (TLR) 7 and retinoic acid-inducible gene 1 (RIG-I) molecules by nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB route). Anti-inflammatory therapies focused on modulating this inflammatory response to "all patients" have not been satisfactory. Steroids should be avoided because they do not improve survival and promote superinfections. Since clinical judgment has often been proven inadequate, interest in the use of biomarkers to monitor host response and to assess severity and complications is growing. It is well known that, if used appropriately, these can be helpful tools to predict not only severity but also mortality. We need more biomarkers that predict host response: it is time to change lactate measurement to proteomics and transcriptomics. Theranostics describes an approach covering both diagnosis and coupled therapy. Death is usually a fatal complication of a dysregulated immune response more than the acute virulence of the infectious agent. Future research demonstrating the usefulness of adjunctive therapy in a subset of critically ill patients with IAV pneumonia is an unmet clinical need. PMID:26936615

  19. Sodium channel β subunits: emerging targets in channelopathies

    PubMed Central

    O’Malley, Heather A.; Isom, Lori L.

    2016-01-01

    Voltage-gated sodium channels (VGSCs) are responsible for initiation and propagation of action potentials in excitable cells. VGSCs in mammalian brain are heterotrimeric complexes of α and β subunits. Originally called “auxiliary,” we now know that β subunit proteins are multifunctional signaling molecules that play roles in both excitable and non-excitable cell types, and with or without the pore-forming α subunit present. β subunits function in VGSC and potassium channel modulation, cell adhesion, and gene regulation, with particularly important roles in brain development. Mutations in the genes encoding β subunits are linked to a number of diseases, including epilepsy, sudden death syndromes like SUDEP and SIDS, and cardiac arrhythmia. While VGSC β subunit-specific drugs have not yet been developed, this protein family is an emerging therapeutic target. PMID:25668026

  20. Sodium channel β subunits: emerging targets in channelopathies.

    PubMed

    O'Malley, Heather A; Isom, Lori L

    2015-01-01

    Voltage-gated sodium channels (VGSCs) are responsible for the initiation and propagation of action potentials in excitable cells. VGSCs in mammalian brain are heterotrimeric complexes of α and β subunits. Although β subunits were originally termed auxiliary, we now know that they are multifunctional signaling molecules that play roles in both excitable and nonexcitable cell types and with or without the pore-forming α subunit present. β subunits function in VGSC and potassium channel modulation, cell adhesion, and gene regulation, with particularly important roles in brain development. Mutations in the genes encoding β subunits are linked to a number of diseases, including epilepsy, sudden death syndromes like SUDEP and SIDS, and cardiac arrhythmia. Although VGSC β subunit-specific drugs have not yet been developed, this protein family is an emerging therapeutic target. PMID:25668026

  1. THE MOLECULAR BIOLOGY OF AVIAN INFLUENZA VIRUS IN SHORT

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Avian influenza virus (AIV) is an important pathogen of poultry as it can cause severe economic losses through disease, including respiratory signs and mortality, and effects on trade. Avian influenza virus is classified as type A influenza, which is a member of the orthomyxoviridae family. Charact...

  2. Abbreviated Pandemic Influenza Planning Template for Primary Care Offices

    SciTech Connect

    HCTT CHE

    2010-01-01

    The Abbreviated Pandemic Influenza Plan Template for Primary Care Provider Offices is intended to assist primary care providers and office managers with preparing their offices for quickly putting a plan in place to handle an increase in patient calls and visits, whether during the 2009-2010 influenza season or future influenza seasons.

  3. Swine as a model for influenza A virus infection

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Influenza A viruses (IAV) infect a variety of hosts, including humans, swine, and various avian species. The annual influenza disease burden in the human population remains significant even with current vaccine usage and much about the pathogenesis and transmission of influenza viruses in human rema...

  4. Marketing paediatric influenza vaccination: results of a major metropolitan trial

    PubMed Central

    Van Buynder, Paul G.; Carcione, Dale; Rettura, Vince; Daly, Alison; Woods, Emily

    2010-01-01

    Please cite this paper as: Van Buynder et al. (2010) Marketing paediatric influenza vaccination: results of a major metropolitan trial. Influenza and Other Respiratory Viruses 5(1), 33–38. Objectives  After a cluster of rapidly fulminant influenza related toddler deaths in a Western Australian metropolis, children aged six to 59 months were offered influenza vaccination in subsequent winters. Some parental resistance was expected and previous poor uptake of paediatric influenza vaccination overseas was noted. A marketing campaign addressing barriers to immunization was developed to maximise uptake. Design  Advertising occurred in major statewide newspapers, via public poster displays and static ‘eye‐lite’ displays, via press releases, via a series of rolling radio advertisements, via direct marketing to child care centres, and via a linked series of web‐sites. Parents were subsequently surveyed to assess reasons for vaccination. Main Outcome Results  The campaign produced influenza vaccination coverage above that previously described elsewhere and led to a proportionate reduction in influenza notifications in this age group compared to previous seasons. Conclusions  Influenza in children comes with significant morbidity and some mortality. Paediatric influenza vaccination is safe, well tolerated and effective if two doses are given. A targeted media campaign can increase vaccine uptake if it reinforces the seriousness of influenza and addresses community ‘myths’ about influenza and influenza vaccine. The lessons learned enabling enhancements of similar programs elsewhere. PMID:21138538

  5. KINETIC PROFILE OF INFLUENZA VIRUS INFECTION IN THREE RAT STRAINS

    EPA Science Inventory

    Abstract

    Influenza infection is a respiratory disease of viral origin that can cause major epidemics in man. The influenza virus infects and damages epithelial cells of the respiratory tract and causes pneumonia. Lung lesions of mice infected with influenza virus resembl...

  6. Colds and the Flu: H1N1 Influenza

    MedlinePlus

    MENU Return to Web version Colds and the Flu | H1N1 Influenza What is H1N1 influenza? H1N1 influenza (also known as swine flu) is an infection caused by ... or illness that is more than “just a cold.” When should I see my doctor? If you’ ...

  7. Perception and Attitudes of Korean Obstetricians about Maternal Influenza Vaccination.

    PubMed

    Noh, Ji Yun; Seo, Yu Bin; Song, Joon Young; Choi, Won Suk; Lee, Jacob; Jung, Eunju; Kang, Seonghui; Choi, Min Joo; Jun, Jiho; Yoon, Jin Gu; Lee, Saem Na; Hyun, Hakjun; Lee, Jin-Soo; Cheong, Hojin; Cheong, Hee Jin; Kim, Woo Joo

    2016-07-01

    Pregnant women are prioritized to receive influenza vaccination. However, the maternal influenza vaccination rate has been low in Korea. To identify potential barriers for the vaccination of pregnant women against influenza, a survey using a questionnaire on the perceptions and attitudes about maternal influenza vaccination was applied to Korean obstetricians between May and August of 2014. A total of 473 respondents participated in the survey. Most respondents (94.8%, 442/466) recognized that influenza vaccination was required for pregnant women. In addition, 92.8% (410/442) respondents knew that the incidence of adverse events following influenza vaccination is not different between pregnant and non-pregnant women. However, 26.5% (124/468) obstetricians strongly recommended influenza vaccination to pregnant women. The concern about adverse events following influenza vaccination was considered as a major barrier for the promotion of maternal influenza vaccination by healthcare providers. Providing professional information and education about maternal influenza vaccination will enhance the perception of obstetricians about influenza vaccination to pregnant women and will be helpful to improve maternal influenza vaccination coverage in Korea. PMID:27366003

  8. Comparative pathology of select agent influenza A virus infections

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Influenza A virus infections may spread rapidly in human populations and cause acute respiratory disease with variable mortality. Two of these influenza viruses have been designated as select agents because of the high case fatality rate: 1918 H1N1 virus and highly pathogenic avian influenza (HPAI) ...

  9. WOULD THE 1918 PANDEMIC INFLUENZA VIRUS BE A THREAT TODAY?

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The 1918 influenza pandemic caused more than 20 million deaths worldwide. Under biosafety level 3Ag containment, a recombinant influenza virus bearing the 1918 influenza virus hemagglutinin (HA) and neuraminidase (NA) was generated. This virus is highly virulent in mice, pointing to the 1918 HA and...

  10. Structure of the iSH2 domain of Human phosphatidylinositol 3-kinase p85 beta Subunit Reveals Conformational Plasticity in the Interhelical Turn Region

    SciTech Connect

    C Schauder; L Ma; R Krug; G Montelione; R Guan

    2011-12-31

    Phosphatidylinositol 3-kinase (PI3K) proteins actively trigger signaling pathways leading to cell growth, proliferation and survival. These proteins have multiple isoforms and consist of a catalytic p110 subunit and a regulatory p85 subunit. The iSH2 domain of the p85 {beta} isoform has been implicated in the binding of nonstructural protein 1 (NS1) of influenza A viruses. Here, the crystal structure of human p85 {beta} iSH2 determined to 3.3 {angstrom} resolution is reported. The structure reveals that this domain mainly consists of a coiled-coil motif. Comparison with the published structure of the bovine p85 {beta} iSH2 domain bound to the influenza A virus nonstructural protein 1 indicates that little or no structural change occurs upon complex formation. By comparing this human p85 {beta} iSH2 structure with the bovine p85 {beta} iSH2 domain, which shares 99% sequence identity, and by comparing the multiple conformations observed within the asymmetric unit of the bovine iSH2 structure, it was found that this coiled-coil domain exhibits a certain degree of conformational variability or 'plasticity' in the interhelical turn region. It is speculated that this plasticity of p85 {beta} iSH2 may play a role in regulating its functional and molecular-recognition properties.

  11. Quantifying the cooperative subunit action in a multimeric membrane receptor

    PubMed Central

    Wongsamitkul, Nisa; Nache, Vasilica; Eick, Thomas; Hummert, Sabine; Schulz, Eckhard; Schmauder, Ralf; Schirmeyer, Jana; Zimmer, Thomas; Benndorf, Klaus

    2016-01-01

    In multimeric membrane receptors the cooperative action of the subunits prevents exact knowledge about the operation and the interaction of the individual subunits. We propose a method that permits quantification of ligand binding to and activation effects of the individual binding sites in a multimeric membrane receptor. The power of this method is demonstrated by gaining detailed insight into the subunit action in olfactory cyclic nucleotide-gated CNGA2 ion channels. PMID:26858151

  12. The elusive definition of pandemic influenza

    PubMed Central

    2011-01-01

    Abstract There has been considerable controversy over the past year, particularly in Europe, over whether the World Health Organization (WHO) changed its definition of pandemic influenza in 2009, after novel H1N1 influenza was identified. Some have argued that not only was the definition changed, but that it was done to pave the way for declaring a pandemic. Others claim that the definition was never changed and that this allegation is completely unfounded. Such polarized views have hampered our ability to draw important conclusions. This impasse, combined with concerns over potential conflicts of interest and doubts about the proportionality of the response to the H1N1 influenza outbreak, has undermined the public trust in health officials and our collective capacity to effectively respond to future disease threats. WHO did not change its definition of pandemic influenza for the simple reason that it has never formally defined pandemic influenza. While WHO has put forth many descriptions of pandemic influenza, it has never established a formal definition and the criteria for declaring a pandemic caused by the H1N1 virus derived from “pandemic phase” definitions, not from a definition of “pandemic influenza”. The fact that despite ten years of pandemic preparedness activities no formal definition of pandemic influenza has been formulated reveals important underlying assumptions about the nature of this infectious disease. In particular, the limitations of “virus-centric” approaches merit further attention and should inform ongoing efforts to “learn lessons” that will guide the response to future outbreaks of novel infectious diseases. PMID:21734768

  13. Predictive Validation of an Influenza Spread Model

    PubMed Central

    Hyder, Ayaz; Buckeridge, David L.; Leung, Brian

    2013-01-01

    Background Modeling plays a critical role in mitigating impacts of seasonal influenza epidemics. Complex simulation models are currently at the forefront of evaluating optimal mitigation strategies at multiple scales and levels of organization. Given their evaluative role, these models remain limited in their ability to predict and forecast future epidemics leading some researchers and public-health practitioners to question their usefulness. The objective of this study is to evaluate the predictive ability of an existing complex simulation model of influenza spread. Methods and Findings We used extensive data on past epidemics to demonstrate the process of predictive validation. This involved generalizing an individual-based model for influenza spread and fitting it to laboratory-confirmed influenza infection data from a single observed epidemic (1998–1999). Next, we used the fitted model and modified two of its parameters based on data on real-world perturbations (vaccination coverage by age group and strain type). Simulating epidemics under these changes allowed us to estimate the deviation/error between the expected epidemic curve under perturbation and observed epidemics taking place from 1999 to 2006. Our model was able to forecast absolute intensity and epidemic peak week several weeks earlier with reasonable reliability and depended on the method of forecasting-static or dynamic. Conclusions Good predictive ability of influenza epidemics is critical for implementing mitigation strategies in an effective and timely manner. Through the process of predictive validation applied to a current complex simulation model of influenza spread, we provided users of the model (e.g. public-health officials and policy-makers) with quantitative metrics and practical recommendations on mitigating impacts of seasonal influenza epidemics. This methodology may be applied to other models of communicable infectious diseases to test and potentially improve their predictive

  14. School-Based Influenza Vaccination: Parents’ Perspectives

    PubMed Central

    Lind, Candace; Russell, Margaret L.; MacDonald, Judy; Collins, Ramona; Frank, Christine J.; Davis, Amy E.

    2014-01-01

    Background School-age children are important drivers of annual influenza epidemics yet influenza vaccination coverage of this population is low despite universal publicly funded influenza vaccination in Alberta, Canada. Immunizing children at school may potentially increase vaccine uptake. As parents are a key stakeholder group for such a program, it is important to consider their concerns. Purpose We explored parents’ perspectives on the acceptability of adding an annual influenza immunization to the immunization program that is currently delivered in Alberta schools, and obtained suggestions for structuring such a program. Participants Forty-eight parents of children aged 5-18 years participated in 9 focus groups. Participants lived in urban areas of the Alberta Health Services Calgary Zone. Findings Three major themes emerged: Advantages of school-based influenza vaccination (SBIV), Disadvantages of SBIV, and Implications for program design & delivery. Advantages were perceived to occur for different populations: children (e.g. emotional support), families (e.g. convenience), the community (e.g. benefits for school and multicultural communities), the health sector (e.g. reductions in costs due to burden of illness) and to society at large (e.g. indirect conduit of information about health services, building structure for pandemic preparedness, building healthy lifestyles). Disadvantages, however, might also occur for children (e.g. older children less likely to be immunized), families (e.g. communication challenges, perceived loss of parental control over information, choices and decisions) and the education sector (loss of instructional time). Nine second-level themes emerged within the major theme of Implications for program design & delivery: program goals/objectives, consent process, stakeholder consultation, age-appropriate program, education, communication, logistics, immunizing agent, and clinic process. Conclusions Parents perceived advantages and

  15. Review Article: Influenza Transmission on Aircraft

    PubMed Central

    Adlhoch, Cornelia

    2016-01-01

    Background: Air travel is associated with the spread of influenza through infected passengers and potentially through in-flight transmission. Contact tracing after exposure to influenza is not performed systematically. We performed a systematic literature review to evaluate the evidence for influenza transmission aboard aircraft. Methods: Using PubMed and EMBASE databases, we identified and critically appraised identified records to assess the evidence of such transmission to passengers seated in close proximity to the index cases. We also developed a bias assessment tool to evaluate the quality of evidence provided in the retrieved studies. Results: We identified 14 peer-reviewed publications describing contact tracing of passengers after possible exposure to influenza virus aboard an aircraft. Contact tracing during the initial phase of the influenza A(H1N1)pdm09 pandemic was described in 11 publications. The studies describe the follow-up of 2,165 (51%) of 4,252 traceable passengers. Altogether, 163 secondary cases were identified resulting in an overall secondary attack rate among traced passengers of 7.5%. Of these secondary cases, 68 (42%) were seated within two rows of the index case. Conclusion: We found an overall moderate quality of evidence for transmission of influenza virus aboard an aircraft. The major limiting factor was the comparability of the studies. A majority of secondary cases was identified at a greater distance than two rows from the index case. A standardized approach for initiating, conducting, and reporting contact tracing could help to increase the evidence base for better assessing influenza transmission aboard aircraft. PMID:27253070

  16. Adolescent Attitudes toward Influenza Vaccination and Vaccine Uptake in a School-Based Influenza Vaccination Intervention: A Mediation Analysis

    ERIC Educational Resources Information Center

    Painter, Julia E.; Sales, Jessica M.; Pazol, Karen; Wingood, Gina M.; Windle, Michael; Orenstein, Walter A.; DiClemente, Ralph J.

    2011-01-01

    Background: School-based vaccination programs may provide an effective strategy to immunize adolescents against influenza. This study examined whether adolescent attitudes toward influenza vaccination mediated the relationship between receipt of a school-based influenza vaccination intervention and vaccine uptake. Methods: Participants were…

  17. Avian influenza in shorebirds: experimental infection of ruddy turnstones (Arenaria interpres) with avian influenza virus

    USGS Publications Warehouse

    Hall, Jeffrey S.; Krauss, Scott; Franson, J. Christian; TeSlaa, Joshua L.; Nashold, Sean W.; Stallknecht, David E.; Webby, Richard J.; Webster, Robert G.

    2013-01-01

    Background: Low pathogenic avian influenza viruses (LPAIV) have been reported in shorebirds, especially at Delaware Bay, USA, during spring migration. However, data on patterns of virus excretion, minimal infectious doses, and clinical outcome are lacking. The ruddy turnstone (Arenaria interpres) is the shorebird species with the highest prevalence of influenza virus at Delaware Bay. Objectives: The primary objective of this study was to experimentally assess the patterns of influenza virus excretion, minimal infectious doses, and clinical outcome in ruddy turnstones. Methods: We experimentally challenged ruddy turnstones using a common LPAIV shorebird isolate, an LPAIV waterfowl isolate, or a highly pathogenic H5N1 avian influenza virus. Cloacal and oral swabs and sera were analyzed from each bird. Results: Most ruddy turnstones had pre-existing antibodies to avian influenza virus, and many were infected at the time of capture. The infectious doses for each challenge virus were similar (103·6–104·16 EID50), regardless of exposure history. All infected birds excreted similar amounts of virus and showed no clinical signs of disease or mortality. Influenza A-specific antibodies remained detectable for at least 2 months after inoculation. Conclusions: These results provide a reference for interpretation of surveillance data, modeling, and predicting the risks of avian influenza transmission and movement in these important hosts.

  18. Protection against divergent influenza H1N1 virus by a centralized influenza hemagglutinin.

    PubMed

    Weaver, Eric A; Rubrum, Adam M; Webby, Richard J; Barry, Michael A

    2011-01-01

    Influenza poses a persistent worldwide threat to the human population. As evidenced by the 2009 H1N1 pandemic, current vaccine technologies are unable to respond rapidly to this constantly diverging pathogen. We tested the utility of adenovirus (Ad) vaccines expressing centralized consensus influenza antigens. Ad vaccines were produced within 2 months and protected against influenza in mice within 3 days of vaccination. Ad vaccines were able to protect at doses as low as 10(7) virus particles/kg indicating that approximately 1,000 human doses could be rapidly generated from standard Ad preparations. To generate broadly cross-reactive immune responses, centralized consensus antigens were constructed against H1 influenza and against H1 through H5 influenza. Twenty full-length H1 HA sequences representing the main branches of the H1 HA phylogenetic tree were used to create a synthetic centralized gene, HA1-con. HA1-con minimizes the degree of sequence dissimilarity between the vaccine and existing circulating viruses. The centralized H1 gene, HA1-con, induced stronger immune responses and better protection against mismatched virus challenges as compared to two wildtype H1 genes. HA1-con protected against three genetically diverse lethal influenza challenges. When mice were challenged with 1934 influenza A/PR/8/34, HA1-con protected 100% of mice while vaccine generated from 2009 A/TX/05/09 only protected 40%. Vaccination with 1934 A/PR/8/34 and 2009 A/TX/05/09 protected 60% and 20% against 1947 influenza A/FM/1/47, respectively, whereas 80% of mice vaccinated with HA1-con were protected. Notably, 80% of mice challenged with 2009 swine flu isolate A/California/4/09 were protected by HA1-con vaccination. These data show that HA1-con in Ad has potential as a rapid and universal vaccine for H1N1 influenza viruses. PMID:21464940

  19. Nasal commensal Staphylococcus epidermidis counteracts influenza virus

    PubMed Central

    Chen, Hui-Wen; Liu, Pei-Feng; Liu, Yu-Tsueng; Kuo, Sherwin; Zhang, Xing-Quan; Schooley, Robert T.; Rohde, Holger; Gallo, Richard L.; Huang, Chun-Ming

    2016-01-01

    Several microbes, including Staphylococcus epidermidis (S. epidermidis), a Gram-positive bacterium, live inside the human nasal cavity as commensals. The role of these nasal commensals in host innate immunity is largely unknown, although bacterial interference in the nasal microbiome may promote ecological competition between commensal bacteria and pathogenic species. We demonstrate here that S. epidermidis culture supernatants significantly suppressed the infectivity of various influenza viruses. Using high-performance liquid chromatography together with mass spectrometry, we identified a giant extracellular matrix-binding protein (Embp) as the major component involved in the anti-influenza effect of S. epidermidis. This anti-influenza activity was abrogated when Embp was mutated, confirming that Embp is essential for S. epidermidis activity against viral infection. We also showed that both S. epidermidis bacterial particles and Embp can directly bind to influenza virus. Furthermore, the injection of a recombinant Embp fragment containing a fibronectin-binding domain into embryonated eggs increased the survival rate of virus-infected chicken embryos. For an in vivo challenge study, prior Embp intranasal inoculation in chickens suppressed the viral titres and induced the expression of antiviral cytokines in the nasal tissues. These results suggest that S. epidermidis in the nasal cavity may serve as a defence mechanism against influenza virus infection. PMID:27306590

  20. Pandemic influenza and the hospitalist: apocalypse when?

    PubMed

    Pile, James C; Gordon, Steven M

    2006-03-01

    Beginning with a cluster of human cases in Hong Kong in 1997, avian influenza (H5N1) has spread progressively through, and beyond, Asia in poultry and other birds; and has resulted in sporadic cases of human disease associated with high mortality. The potential for H5N1 influenza to cause a pandemic of human disease continues to be the subject of intense scrutiny by both the media and the scientific community. While the likelihood of such a prospect is uncertain, the inevitability of future pandemics of influenza is clear. Planning for the eventuality of a virulent influenza pandemic at the local, national and global level is critical to limiting the mortality and morbidity of such an occurrence. Hospitalists have a key role to play in institutional efforts to prepare for a influenza pandemic, and should be aware of lessons that my be applied from both the response to Hurricane Katrina, as well as the severe acute respiratory syndrome (SARS) epidemic. PMID:17219482

  1. Influenza Vaccines: A Moving Interdisciplinary Field

    PubMed Central

    Schotsaert, Michael; García-Sastre, Adolfo

    2014-01-01

    Vaccination is by far the most effective way of preventing morbidity and mortality due to infection of the upper respiratory tract by influenza virus. Current vaccines require yearly vaccine updates as the influenza virus can escape vaccine-induced humoral immunity due to the antigenic variability of its surface antigens. In case of a pandemic, new vaccines become available too late with current vaccine practices. New technologies that allow faster production of vaccine seed strains in combination with alternative production platforms and vaccine formulations may shorten the time gap between emergence of a new influenza virus and a vaccine becoming available. Adjuvants may allow antigen-sparing, allowing more people to be vaccinated with current vaccine production capacity. Adjuvants and universal vaccines can target immune responses to more conserved influenza epitopes, which eventually will result in broader protection for a longer time. In addition, further immunological studies are needed to gain insights in the immune features that contribute to protection from influenza-related disease and mortality, allowing redefinition of correlates of protection beyond virus neutralization in vitro. PMID:25302957

  2. Delaying the International Spread of Pandemic Influenza

    PubMed Central

    Cooper, Ben S; Pitman, Richard J; Edmunds, W. John; Gay, Nigel J

    2006-01-01

    Background The recent emergence of hypervirulent subtypes of avian influenza has underlined the potentially devastating effects of pandemic influenza. Were such a virus to acquire the ability to spread efficiently between humans, control would almost certainly be hampered by limited vaccine supplies unless global spread could be substantially delayed. Moreover, the large increases that have occurred in international air travel might be expected to lead to more rapid global dissemination than in previous pandemics. Methods and Findings To evaluate the potential of local control measures and travel restrictions to impede global dissemination, we developed stochastic models of the international spread of influenza based on extensions of coupled epidemic transmission models. These models have been shown to be capable of accurately forecasting local and global spread of epidemic and pandemic influenza. We show that under most scenarios restrictions on air travel are likely to be of surprisingly little value in delaying epidemics, unless almost all travel ceases very soon after epidemics are detected. Conclusions Interventions to reduce local transmission of influenza are likely to be more effective at reducing the rate of global spread and less vulnerable to implementation delays than air travel restrictions. Nevertheless, under the most plausible scenarios, achievable delays are small compared with the time needed to accumulate substantial vaccine stocks. PMID:16640458

  3. Compilation of small ribosomal subunit RNA structures.

    PubMed Central

    Neefs, J M; Van de Peer, Y; De Rijk, P; Chapelle, S; De Wachter, R

    1993-01-01

    The database on small ribosomal subunit RNA structure contained 1804 nucleotide sequences on April 23, 1993. This number comprises 365 eukaryotic, 65 archaeal, 1260 bacterial, 30 plastidial, and 84 mitochondrial sequences. These are stored in the form of an alignment in order to facilitate the use of the database as input for comparative studies on higher-order structure and for reconstruction of phylogenetic trees. The elements of the postulated secondary structure for each molecule are indicated by special symbols. The database is available on-line directly from the authors by ftp and can also be obtained from the EMBL nucleotide sequence library by electronic mail, ftp, and on CD ROM disk. PMID:8332525

  4. PI3Kγ Is Critical for Dendritic Cell-Mediated CD8+ T Cell Priming and Viral Clearance during Influenza Virus Infection

    PubMed Central

    Nobs, Samuel Philip; Schneider, Christoph; Heer, Alex Kaspar; Huotari, Jatta; Helenius, Ari; Kopf, Manfred

    2016-01-01

    Phosphoinositide-3-kinases have been shown to be involved in influenza virus pathogenesis. They are targeted directly by virus proteins and are essential for efficient viral replication in infected lung epithelial cells. However, to date the role of PI3K signaling in influenza infection in vivo has not been thoroughly addressed. Here we show that one of the PI3K subunits, p110γ, is in fact critically required for mediating the host’s antiviral response. PI3Kγ deficient animals exhibit a delayed viral clearance and increased morbidity during respiratory infection with influenza virus. We demonstrate that p110γ is required for the generation and maintenance of potent antiviral CD8+ T cell responses through the developmental regulation of pulmonary cross-presenting CD103+ dendritic cells under homeostatic and inflammatory conditions. The defect in lung dendritic cells leads to deficient CD8+ T cell priming, which is associated with higher viral titers and more severe disease course during the infection. We thus identify PI3Kγ as a novel key host protective factor in influenza virus infection and shed light on an unappreciated layer of complexity concerning the role of PI3K signaling in this context. PMID:27030971

  5. Dynamic regulation of β1 subunit trafficking controls vascular contractility

    PubMed Central

    Leo, M. Dennis; Bannister, John P.; Narayanan, Damodaran; Nair, Anitha; Grubbs, Jordan E.; Gabrick, Kyle S.; Boop, Frederick A.; Jaggar, Jonathan H.

    2014-01-01

    Ion channels composed of pore-forming and auxiliary subunits control physiological functions in virtually all cell types. A conventional view is that channels assemble with their auxiliary subunits before anterograde plasma membrane trafficking of the protein complex. Whether the multisubunit composition of surface channels is fixed following protein synthesis or flexible and open to acute and, potentially, rapid modulation to control activity and cellular excitability is unclear. Arterial smooth muscle cells (myocytes) express large-conductance Ca2+-activated potassium (BK) channel α and auxiliary β1 subunits that are functionally significant modulators of arterial contractility. Here, we show that native BKα subunits are primarily (∼95%) plasma membrane-localized in human and rat arterial myocytes. In contrast, only a small fraction (∼10%) of total β1 subunits are located at the cell surface. Immunofluorescence resonance energy transfer microscopy demonstrated that intracellular β1 subunits are stored within Rab11A-postive recycling endosomes. Nitric oxide (NO), acting via cGMP-dependent protein kinase, and cAMP-dependent pathways stimulated rapid (≤1 min) anterograde trafficking of β1 subunit-containing recycling endosomes, which increased surface β1 almost threefold. These β1 subunits associated with surface-resident BKα proteins, elevating channel Ca2+ sensitivity and activity. Our data also show that rapid β1 subunit anterograde trafficking is the primary mechanism by which NO activates myocyte BK channels and induces vasodilation. In summary, we show that rapid β1 subunit surface trafficking controls functional BK channel activity in arterial myocytes and vascular contractility. Conceivably, regulated auxiliary subunit trafficking may control ion channel activity in a wide variety of cell types. PMID:24464482

  6. Differential age susceptibility to influenza B/Victoria lineage viruses in the 2015 Australian influenza season.

    PubMed

    Barr, Ian G; Vijaykrishna, Dhanasekaran; Sullivan, Sheena G

    2016-01-01

    Influenza B viruses make up an important part of the burden from seasonal influenza globally. The 2015 season in Australia saw an unusual predominance of influenza B with a distinctive switch during the season from B/Yamagata/16/88 lineage viruses to B/Victoria/2/87 lineage viruses. We also noted significant differences in the age groups infected by the different B lineages, with B/Victoria infecting a younger population than B/Yamagata, that could not be explained by potential prior exposure. PMID:26848118

  7. Assessing the burden of paediatric influenza in Europe: the European Paediatric Influenza Analysis (EPIA) project

    PubMed Central

    Paget, W. John; Casas, Inmaculada; Donker, Gé; Edelman, Laurel; Fleming, Douglas; Larrauri, Amparo; Meijer, Adam; Puzelli, Simona; Rizzo, Caterina; Simonsen, Lone

    2010-01-01

    The European Paediatric Influenza Analysis (EPIA) project is a multi-country project that was created to collect, analyse and present data regarding the paediatric influenza burden in European countries, with the purpose of providing the necessary information to make evidence-based decisions regarding influenza immunisation recommendations for children. The initial approach taken is based on existing weekly virological and age-specific influenza-like illness (ILI) data from surveillance networks across Europe. We use a multiple regression model guided by longitudinal weekly patterns of influenza virus to attribute the weekly ILI consultation incidence pattern to each influenza (sub)type, while controlling for the effect of respiratory syncytial virus (RSV) epidemics. Modelling the ILI consultation incidence during 2002/2003–2008 revealed that influenza infections that presented for medical attention as ILI affected between 0.3% and 9.8% of children aged 0–4 and 5–14 years in England, Italy, The Netherlands and Spain in an average season. With the exception of Spain, these rates were always higher in children aged 0–4 years. Across the six seasons analysed (five seasons were analysed from the Italian data), the model attributed 47–83% of the ILI burden in primary care to influenza virus infection in the various countries, with the A(H3N2) virus playing the most important role, followed by influenza viruses B and A(H1N1). National season averages from the four countries studied indicated that between 0.4% and 18% of children consulted a physician for ILI, with the percentage depending on the country and health care system. Influenza virus infections explained the majority of paediatric ILI consultations in all countries. The next step will be to apply the EPIA modelling approach to severe outcomes indicators (i.e. hospitalisations and mortality data) to generate a complete range of mild and severe influenza burden estimates needed for decision making

  8. Increased defibrillator therapies during influenza season in patients without influenza vaccines

    PubMed Central

    Singh, Sheldon M.; de Souza, Russell J.; Kumareswaran, Ramanan

    2015-01-01

    Background The association between influenza vaccination and implantable cardiac defibrillator (ICD) therapies during influenza season is not known and is described in this study. Understanding this association is important since reduction in ICD therapies during influenza season via use of influenza vaccination would benefit patients physically and psychologically. Methods Patients presenting to the Sunnybrook Health Sciences Center ICD clinic between September 1st, 2011 and November 31st, 2011 were asked to complete a survey evaluating their use of the influenza vaccine. The number of patients with any ICD therapy and the total number of ICD therapies in the six months before and the three months during the 2010–2011 influenza season were determined. Poisson regression analysis was employed to assess differences in the average number of ICD therapies received during the influenza season based on vaccine status (vaccinated vs. unvaccinated). The analysis was repeated after limiting the cohort to patients with a left ventricular ejection fraction ≤35%. Results A total of 229 patients completed the survey, 78% of whom received the influenza vaccine. Four patients had more than one ICD shock during the study period. Electrical storm was rare (n=2). A trend toward more ICD therapies (unadjusted incident rate ratio (IRR)=3.2; P=0.07) and appropriate ICD shocks (unadjusted IRR=9.0; P=0.17) was noted for unvaccinated compared to vaccinated patients. This association persisted when analysis was limited to patients with a left ventricular ejection fraction ≤35% (all ICD therapies: unadjusted IRR=5.8; P=0.045; adjusted IRR=2.6; P=0.33). No patient who received the influenza vaccine, and had a reduced ejection fraction, received an approprite ICD shock during influenza season (unadjusted P<0.002). Conclusion A trend toward more ICD therapies during influenza season was observed in patients who did not receive the influenza vaccine compared to those who did. The

  9. The prevention and control of avian influenza: The avian influenza coordinated agriculture project1

    PubMed Central

    Cardona, C.; Slemons, R.; Perez, D.

    2015-01-01

    The Avian Influenza Coordinated Agriculture Project (AICAP) entitled “Prevention and Control of Avian Influenza in the US” strives to be a significant point of reference for the poultry industry and the general public in matters related to the biology, risks associated with, and the methods used to prevent and control avian influenza. To this end, AICAP has been remarkably successful in generating research data, publications through an extensive network of university- and agency-based researchers, and extending findings to stakeholders. An overview of the highlights of AICAP research is presented. PMID:19276431

  10. Influenza epidemiology, vaccine coverage and vaccine effectiveness in sentinel Australian hospitals in 2013: the Influenza Complications Alert Network.

    PubMed

    Cheng, Allen C; Dwyer, Dominic E; Holmes, Mark; Irving, Lois B; Brown, Simon Ga; Waterer, Grant W; Korman, Tony M; Hunter, Cameron; Hewagama, Saliya; Friedman, Nadia D; Wark, Peter A; Simpson, Graham; Upham, John W; Bowler, Simon D; Senenayake, Sanjaya N; Kotsimbos, Tom C; Kelly, Paul M

    2014-06-01

    The National Influenza Program aims to reduce serious morbidity and mortality from influenza by providing public funding for vaccination to at-risk groups. The Influenza Complications Alert Network (FluCAN) is a sentinel hospital-based surveillance program that operates at 14 sites in all states and territories in Australia. This report summarises the epidemiology of hospitalisations with confirmed influenza, estimates vaccine coverage and influenza vaccine protection against hospitalisation with influenza during the 2013 influenza season. In this observational study, cases were defined as patients admitted to one of the sentinel hospitals, with influenza confirmed by nucleic acid testing. Controls were patients who had acute respiratory illnesses who were test-negative for influenza. Vaccine effectiveness was estimated as 1 minus the odds ratio of vaccination in case patients compared with control patients, after adjusting for known confounders. During the period 5 April to 31 October 2012, 631 patients were admitted with confirmed influenza at the 14 FluCAN sentinel hospitals. Of these, 31% were more than 65 years of age, 9.5% were Indigenous Australians, 4.3% were pregnant and 77% had chronic co-morbidities. Influenza B was detected in 30% of patients. Vaccination coverage was estimated at 81% in patients more than 65 years of age but only 49% in patients aged less than 65 years with chronic comorbidities. Vaccination effectiveness against hospitalisation with influenza was estimated at 50% (95% confidence interval: 33%, 63%, P<0.001). We detected a significant number of hospital admissions with confirmed influenza in a national observational study. Vaccine coverage was incomplete in at-risk groups, particularly non-elderly patients with medical comorbidities. Our results suggest that the seasonal influenza vaccine was moderately protective against hospitalisation with influenza in the 2013 season. PMID:25222208

  11. School-Located Influenza Vaccination Reduces Community Risk for Influenza and Influenza-Like Illness Emergency Care Visits

    PubMed Central

    Tran, Cuc H.; Sugimoto, Jonathan D.; Pulliam, Juliet R. C.; Ryan, Kathleen A.; Myers, Paul D.; Castleman, Joan B.; Doty, Randell; Johnson, Jackie; Stringfellow, Jim; Kovacevich, Nadia; Brew, Joe; Cheung, Lai Ling; Caron, Brad; Lipori, Gloria; Harle, Christopher A.; Alexander, Charles; Yang, Yang; Longini, Ira M.; Halloran, M. Elizabeth; Morris, J. Glenn; Small, Parker A.

    2014-01-01

    Background School-located influenza vaccination (SLIV) programs can substantially enhance the sub-optimal coverage achieved under existing delivery strategies. Randomized SLIV trials have shown these programs reduce laboratory-confirmed influenza among both vaccinated and unvaccinated children. This work explores the effectiveness of a SLIV program in reducing the community risk of influenza and influenza-like illness (ILI) associated emergency care visits. Methods For the 2011/12 and 2012/13 influenza seasons, we estimated age-group specific attack rates (AR) for ILI from routine surveillance and census data. Age-group specific SLIV program effectiveness was estimated as one minus the AR ratio for Alachua County versus two comparison regions: the 12 county region surrounding Alachua County, and all non-Alachua counties in Florida. Results Vaccination of ∼50% of 5–17 year-olds in Alachua reduced their risk of ILI-associated visits, compared to the rest of Florida, by 79% (95% confidence interval: 70, 85) in 2011/12 and 71% (63, 77) in 2012/13. The greatest indirect effectiveness was observed among 0–4 year-olds, reducing AR by 89% (84, 93) in 2011/12 and 84% (79, 88) in 2012/13. Among all non-school age residents, the estimated indirect effectiveness was 60% (54, 65) and 36% (31, 41) for 2011/12 and 2012/13. The overall effectiveness among all age-groups was 65% (61, 70) and 46% (42, 50) for 2011/12 and 2012/13. Conclusion Wider implementation of SLIV programs can significantly reduce the influenza-associated public health burden in communities. PMID:25489850

  12. Influenza-attributable burden in United Kingdom primary care.

    PubMed

    Fleming, D M; Taylor, R J; Haguinet, F; Schuck-Paim, C; Logie, J; Webb, D J; Lustig, R L; Matias, G

    2016-02-01

    Influenza is rarely laboratory-confirmed and the outpatient influenza burden is rarely studied due to a lack of suitable data. We used the Clinical Practice Research Datalink (CPRD) and surveillance data from Public Health England in a linear regression model to assess the number of persons consulting UK general practitioners (GP episodes) for respiratory illness, otitis media and antibiotic prescriptions attributable to influenza during 14 seasons, 1995-2009. In CPRD we ascertained influenza vaccination status in each season and risk status (conditions associated with severe influenza outcomes). Seasonal mean estimates of influenza-attributable GP episodes in the UK were 857 996 for respiratory disease including 68 777 for otitis media, with wide inter-seasonal variability. In an average season, 2·4%/0·5% of children aged <5 years and 1·3%/0·1% of seniors aged ⩾75 years had a GP episode for respiratory illness attributed to influenza A/B. Two-thirds of influenza-attributable GP episodes were estimated to result in prescription of antibiotics. These estimates are substantially greater than those derived from clinically reported influenza-like illness in surveillance programmes. Because health service costs of influenza are largely borne in general practice, these are important findings for cost-benefit assessment of influenza vaccination programmes. PMID:26168005

  13. Absolute Humidity and the Seasonality of Influenza (Invited)

    NASA Astrophysics Data System (ADS)

    Shaman, J. L.; Pitzer, V.; Viboud, C.; Grenfell, B.; Goldstein, E.; Lipsitch, M.

    2010-12-01

    Much of the observed wintertime increase of mortality in temperate regions is attributed to seasonal influenza. A recent re-analysis of laboratory experiments indicates that absolute humidity strongly modulates the airborne survival and transmission of the influenza virus. Here we show that the onset of increased wintertime influenza-related mortality in the United States is associated with anomalously low absolute humidity levels during the prior weeks. We then use an epidemiological model, in which observed absolute humidity conditions temper influenza transmission rates, to successfully simulate the seasonal cycle of observed influenza-related mortality. The model results indicate that direct modulation of influenza transmissibility by absolute humidity alone is sufficient to produce this observed seasonality. These findings provide epidemiological support for the hypothesis that absolute humidity drives seasonal variations of influenza transmission in temperate regions. In addition, we show that variations of the basic and effective reproductive numbers for influenza, caused by seasonal changes in absolute humidity, are consistent with the general timing of pandemic influenza outbreaks observed for 2009 A/H1N1 in temperate regions. Indeed, absolute humidity conditions correctly identify the region of the United States vulnerable to a third, wintertime wave of pandemic influenza. These findings suggest that the timing of pandemic influenza outbreaks is controlled by a combination of absolute humidity conditions, levels of susceptibility and changes in population mixing and contact rates.

  14. Influenza: Can we cope better with the unpredictable?

    PubMed Central

    Dos Santos, Gaël; Neumeier, Elisabeth; Bekkat-Berkani, Rafik

    2016-01-01

    Abstract Seasonal influenza vaccines are unique because they are regularly reformulated and prepared in anticipation of the upcoming influenza season. Selection of vaccine strains occurs in advance of the influenza season, allowing time for vaccine production. Influenza viruses constantly evolve, and mismatches between vaccine strains and circulating strains have occurred in the past, impacting on vaccine effectiveness. The public health impact of a mismatch depends on multiple factors including strain virulence and transmission dynamics, pre-existing population immunity to the drift strain, and cross-reactivity induced by vaccination. Influenza vaccine effectiveness thus varies unpredictably from year to year, and may differ across European and northern American regions. Here we highlight the unpredictability associated with influenza virus circulation and present a comprehensive picture of circulating influenza strains in the northern hemisphere as compared to WHO recommendations for vaccine strains over the last 15 y. In years when vaccine mismatch occurs, such as the 2014–15 influenza season, public health agencies continue to recommend influenza vaccination as the preferred means by which to protect against influenza and influenza-associated complications. Research is on-going to optimise strain selection and vaccine composition to improve effectiveness. PMID:26360135

  15. Influenza outbreaks during World Youth Day 2008 mass gathering.

    PubMed

    Blyth, Christopher C; Foo, Hong; van Hal, Sebastiaan J; Hurt, Aeron C; Barr, Ian G; McPhie, Kenneth; Armstrong, Paul K; Rawlinson, William D; Sheppeard, Vicky; Conaty, Stephen; Staff, Michael; Dwyer, Dominic E

    2010-05-01

    Influenza outbreaks during mass gatherings have been rarely described, and detailed virologic assessment is lacking. An influenza outbreak occurred during World Youth Day in Sydney, Australia, July 2008 (WYD2008). We assessed epidemiologic data and respiratory samples collected from attendees who sought treatment for influenza-like illness at emergency clinics in Sydney during this outbreak. Isolated influenza viruses were compared with seasonal influenza viruses from the 2008 influenza season. From 100 infected attendees, numerous strains were identified: oseltamivir-resistant influenza A (H1N1) viruses, oseltamivir-sensitive influenza A (H1N1) viruses, influenza A (H3N2) viruses, and strains from both influenza B lineages (B/Florida/4/2006-like and B/Malaysia/2506/2004-like). Novel viruses were introduced, and pre-WYD2008 seasonal viruses were amplified. Viruses isolated at mass gatherings can have substantial, complex, and unpredictable effects on community influenza activity. Greater flexibility by public health authorities and hospitals is required to appropriately manage and contain these outbreaks. PMID:20409371

  16. Knowledge about pandemic influenza preparedness among vulnerable migrants in Thailand.

    PubMed

    Hickey, Jason E; Gagnon, Anita J; Jitthai, Nigoon

    2016-03-01

    This study was designed to assess factors associated with a high level of knowledge about influenza among displaced persons and labor migrants in Thailand. We conducted a cross-sectional study of 797 documented and undocumented migrants thought to be vulnerable to influenza during the early stages of the 2009 H1N1 pandemic. Data were collected on socio-demographic factors, migration status, health information sources, barriers to accessing public healthcare services and influenza-related knowledge using a 201-item interviewer-assisted questionnaire. Among the different types of influenza, participants' awareness of avian influenza was greatest (81%), followed by H1N1 (78%), human influenza (61%) and pandemic influenza (35%). Logistic regression analyses identified 11 factors that significantly predicted a high level of knowledge about influenza. Six or more years of education completed [odds ratio (OR) 6.89 (95% confidence interval (CI) 3.58-13.24)] and recent participation in an influenza prevention activity [OR 5.27 (95% CI 2.78-9.98)] were the strongest predictors. Recommendations to aid public health efforts toward pandemic mitigation and prevention include increasing accessibility of education options for migrants and increasing frequency and accessibility of influenza prevention activities, such as community outreach and meetings. Future research should seek to identify which influenza prevention activities and education materials are most effective. PMID:25204452

  17. Isolation of Single-Stranded DNA Aptamers That Distinguish Influenza Virus Hemagglutinin Subtype H1 from H5

    PubMed Central

    Yim, Sanggyu; Jeong, Yong-Joo

    2015-01-01

    Surface protein hemagglutinin (HA) mediates the binding of influenza virus to host cell receptors containing sialic acid, facilitating the entry of the virus into host cells. Therefore, the HA protein is regarded as a suitable target for the development of influenza virus detection devices. In this study, we isolated single-stranded DNA (ssDNA) aptamers binding to the HA1 subunit of subtype H1 (H1-HA1), but not to the HA1 subunit of subtype H5 (H5-HA1), using a counter-systematic evolution of ligands by exponential enrichment (counter-SELEX) procedure. Enzyme-linked immunosorbent assay and surface plasmon resonance studies showed that the selected aptamers bind tightly to H1-HA1 with dissociation constants in the nanomolar range. Western blot analysis demonstrated that the aptamers were binding to H1-HA1 in a concentration-dependent manner, yet were not binding to H5-HA1. Interestingly, the selected aptamers contained G-rich sequences in the central random nucleotides region. Further biophysical analysis showed that the G-rich sequences formed a G-quadruplex structure, which is a distinctive structure compared to the starting ssDNA library. Using flow cytometry analysis, we found that the aptamers did not bind to the receptor-binding site of H1-HA1. These results indicate that the selected aptamers that distinguish H1-HA1 from H5-HA1 can be developed as unique probes for the detection of the H1 subtype of influenza virus. PMID:25901739

  18. Epidemiology of Hospital Admissions with Influenza during the 2013/2014 Northern Hemisphere Influenza Season: Results from the Global Influenza Hospital Surveillance Network

    PubMed Central

    Puig-Barberà, Joan; Natividad-Sancho, Angels; Trushakova, Svetlana; Sominina, Anna; Pisareva, Maria; Ciblak, Meral A.; Badur, Selim; Yu, Hongjie; Cowling, Benjamin J.; El Guerche-Séblain, Clotilde; Mira-Iglesias, Ainara; Kisteneva, Lidiya; Stolyarov, Kirill; Yurtcu, Kubra; Feng, Luzhao; López-Labrador, Xavier; Burtseva, Elena

    2016-01-01

    Background The Global Influenza Hospital Surveillance Network was established in 2012 to obtain valid epidemiologic data on hospital admissions with influenza-like illness. Here we describe the epidemiology of admissions with influenza within the Northern Hemisphere sites during the 2013/2014 influenza season, identify risk factors for severe outcomes and complications, and assess the impact of different influenza viruses on clinically relevant outcomes in at-risk populations. Methods Eligible consecutive admissions were screened for inclusion at 19 hospitals in Russia, Turkey, China, and Spain using a prospective, active surveillance approach. Patients that fulfilled a common case definition were enrolled and epidemiological data were collected. Risk factors for hospitalization with laboratory-confirmed influenza were identified by multivariable logistic regression. Findings 5303 of 9507 consecutive admissions were included in the analysis. Of these, 1086 were influenza positive (534 A(H3N2), 362 A(H1N1), 130 B/Yamagata lineage, 3 B/Victoria lineage, 40 untyped A, and 18 untyped B). The risk of hospitalization with influenza (adjusted odds ratio [95% confidence interval]) was elevated for patients with cardiovascular disease (1.63 [1.33–2.02]), asthma (2.25 [1.67–3.03]), immunosuppression (2.25 [1.23–4.11]), renal disease (2.11 [1.48–3.01]), liver disease (1.94 [1.18–3.19], autoimmune disease (2.97 [1.58–5.59]), and pregnancy (3.84 [2.48–5.94]). Patients without comorbidities accounted for 60% of admissions with influenza. The need for intensive care or in-hospital death was not significantly different between patients with or without influenza. Influenza vaccination was associated with a lower risk of confirmed influenza (adjusted odds ratio = 0.61 [0.48–0.77]). Conclusions Influenza infection was detected among hospital admissions with and without known risk factors. Pregnancy and underlying comorbidity increased the risk of detecting influenza

  19. Replication and transmission of influenza viruses in Japanese quail

    PubMed Central

    Makarova, Natalia V.; Ozaki, Hiroishi; Kida, Hiroshi; Webster, Robert G.; Perez, Daniel R.

    2015-01-01

    Quail have emerged as a potential intermediate host in the spread of avian influenza A viruses in poultry in Hong Kong. To better understand this possible role, we tested the replication and transmission in quail of influenza A viruses of all 15 HA subtypes. Quail supported the replication of at least 14 subtypes. Influenza A viruses replicated predominantly in the respiratory tract. Transmission experiments suggested that perpetuation of avian influenza viruses in quail requires adaptation. Swine influenza viruses were isolated from the respiratory tract of quail at low levels. There was no evidence of human influenza A or B virus replication. Interestingly, a human–avian recombinant containing the surface glycoprotein genes of a quail virus and the internal genes of a human virus replicated and transmitted readily in quail; therefore, quail could function as amplifiers of influenza virus reassortants that have the potential to infect humans and/or other mammalian species. PMID:12788625

  20. Protective effects of phillyrin against influenza A virus in vivo.

    PubMed

    Qu, Xin-Yan; Li, Qing-Jun; Zhang, Hui-Min; Zhang, Xiao-Juan; Shi, Peng-Hui; Zhang, Xiu-Juan; Yang, Jing; Zhou, Zhe; Wang, Sheng-Qi

    2016-07-01

    Influenza A virus infection represents a great threat to public health. However, owing to side effects and the emergence of resistant virus strains, the use of currently available anti-influenza drugs may be limited. In order to identify novel anti-influenza drugs, we investigated the antiviral effects of phillyrin against influenza A virus infection in vivo. The mean survival time, lung index, viral titers, influenza hemagglutinin (HA) protein and serum cytokines levels, and histopathological changes in lung tissue were examined. Administration of phillyrin at a dose of 20 mg/kg/day for 3 days significantly prolonged the mean survival time, reduced the lung index, decreased the virus titers and interleukin-6 levels, reduced the expression of HA, and attenuated lung tissue damage in mice infected with influenza A virus. Taken together, these data showed that phillyrin had potential protective effects against infection caused by influenza A virus. PMID:27323762

  1. Influenza B vaccine lineage selection—An optimized trivalent vaccine

    PubMed Central

    Mosterín Höpping, Ana; Fonville, Judith M.; Russell, Colin A.; James, Sarah; Smith, Derek J.

    2016-01-01

    Epidemics of seasonal influenza viruses cause considerable morbidity and mortality each year. Various types and subtypes of influenza circulate in humans and evolve continuously such that individuals at risk of serious complications need to be vaccinated annually to keep protection up to date with circulating viruses. The influenza vaccine in most parts of the world is a trivalent vaccine, including an antigenically representative virus of recently circulating influenza A/H3N2, A/H1N1, and influenza B viruses. However, since the 1970s influenza B has split into two antigenically distinct lineages, only one of which is represented in the annual trivalent vaccine at any time. We describe a lineage selection strategy that optimizes protection against influenza B using the standard trivalent vaccine as a potentially cost effective alternative to quadrivalent vaccines. PMID:26896685

  2. Oseltamivir for influenza infection in children: risks and benefits.

    PubMed

    Esposito, Susanna; Principi, Nicola

    2016-01-01

    Influenza is a common disease affecting many children each year. In a number of cases, particularly in children <2 years old and in those with severe chronic underlying disease, influenza can be complicated by lower respiratory tract infections, acute otitis media, rhinosinusitis, febrile seizures, dehydration or encephalopathy. Oseltamivir is the influenza virus drug that is most commonly studied in children for both the treatment and prevention of influenza. To avoid the risk that children with mild influenza or patients suffering from different viral infections receive oseltamivir, oseltamivir treatment should be recommended only in severe influenza cases, especially if confirmed by reliable laboratory tests. However, therapy must be initiated considering the risk of complications and the presence of severe clinical manifestations at age- and weight-appropriate doses. Because the vaccine remains the best option for preventing influenza and its complications, prophylaxis using oseltamivir should only be considered in select patients. PMID:26616633

  3. Inhibitors of influenza viruses replication: a patent evaluation (WO2013019828).

    PubMed

    Xie, Yuanchao; Song, Weiguo; Xiao, Weidong; Gu, Changjuan; Xu, Wenfang

    2013-11-01

    A series of compounds incorporating two aromatic heterocycles were prepared as inhibitors of influenza virus replication in the patent. Some of them presented potent activity against influenza virus in Madin-Darby canine kidney (MDCK) cells and in influenza therapeutic mouse model. These compounds in the patent were also defined to be pharmaceutically acceptable salts and pharmaceutical compositions that were claimed to be useful for treating influenza. In view of the threat of influenza pandemic, it is necessary to discover new anti-influenza drugs. Although there is a lack of essential biological data and the molecular mechanisms are not clear, these compounds with potent antiviral activity stand for a new type of anti-influenza agents and deserve further studies. PMID:23967861

  4. Evidence for a heritable predisposition to death due to influenza.

    PubMed

    Albright, Frederick S; Orlando, Patricia; Pavia, Andrew T; Jackson, George G; Cannon Albright, Lisa A

    2008-01-01

    Animal model studies and human epidemiological studies have shown that some infectious diseases develop primarily in individuals with an inherited predisposition. A heritable contribution to the development of severe influenza virus infection (i.e., that which results in death) has not previously been hypothesized or tested. Evidence for a heritable contribution to death due to influenza was examined using a resource consisting of a genealogy of the Utah population linked to death certificates in Utah over a period of 100 years. The relative risks of death due to influenza were estimated for the relatives of 4,855 individuals who died of influenza. Both close and distant relatives of individuals who died of influenza were shown to have a significantly increased risk of dying of influenza, consistent with a combination of shared exposure and genetic effects. These data provide strong support for a heritable contribution to predisposition to death due to influenza. PMID:18171280

  5. Liposome-Based Adjuvants for Subunit Vaccines: Formulation Strategies for Subunit Antigens and Immunostimulators

    PubMed Central

    Tandrup Schmidt, Signe; Foged, Camilla; Smith Korsholm, Karen; Rades, Thomas; Christensen, Dennis

    2016-01-01

    The development of subunit vaccines has become very attractive in recent years due to their superior safety profiles as compared to traditional vaccines based on live attenuated or whole inactivated pathogens, and there is an unmet medical need for improved vaccines and vaccines against pathogens for which no effective vaccines exist. The subunit vaccine technology exploits pathogen subunits as antigens, e.g., recombinant proteins or synthetic peptides, allowing for highly specific immune responses against the pathogens. However, such antigens are usually not sufficiently immunogenic to induce protective immunity, and they are often combined with adjuvants to ensure robust immune responses. Adjuvants are capable of enhancing and/or modulating immune responses by exposing antigens to antigen-presenting cells (APCs) concomitantly with conferring immune activation signals. Few adjuvant systems have been licensed for use in human vaccines, and they mainly stimulate humoral immunity. Thus, there is an unmet demand for the development of safe and efficient adjuvant systems that can also stimulate cell-mediated immunity (CMI). Adjuvants constitute a heterogeneous group of compounds, which can broadly be classified into delivery systems or immunostimulators. Liposomes are versatile delivery systems for antigens, and they can carefully be customized towards desired immune profiles by combining them with immunostimulators and optimizing their composition, physicochemical properties and antigen-loading mode. Immunostimulators represent highly diverse classes of molecules, e.g., lipids, nucleic acids, proteins and peptides, and they are ligands for pattern-recognition receptors (PRRs), which are differentially expressed on APC subsets. Different formulation strategies might thus be required for incorporation of immunostimulators and antigens, respectively, into liposomes, and the choice of immunostimulator should ideally be based on knowledge regarding the specific PRR

  6. Liposome-Based Adjuvants for Subunit Vaccines: Formulation Strategies for Subunit Antigens and Immunostimulators.

    PubMed

    Tandrup Schmidt, Signe; Foged, Camilla; Korsholm, Karen Smith; Rades, Thomas; Christensen, Dennis

    2016-01-01

    The development of subunit vaccines has become very attractive in recent years due to their superior safety profiles as compared to traditional vaccines based on live attenuated or whole inactivated pathogens, and there is an unmet medical need for improved vaccines and vaccines against pathogens for which no effective vaccines exist. The subunit vaccine technology exploits pathogen subunits as antigens, e.g., recombinant proteins or synthetic peptides, allowing for highly specific immune responses against the pathogens. However, such antigens are usually not sufficiently immunogenic to induce protective immunity, and they are often combined with adjuvants to ensure robust immune responses. Adjuvants are capable of enhancing and/or modulating immune responses by exposing antigens to antigen-presenting cells (APCs) concomitantly with conferring immune activation signals. Few adjuvant systems have been licensed for use in human vaccines, and they mainly stimulate humoral immunity. Thus, there is an unmet demand for the development of safe and efficient adjuvant systems that can also stimulate cell-mediated immunity (CMI). Adjuvants constitute a heterogeneous group of compounds, which can broadly be classified into delivery systems or immunostimulators. Liposomes are versatile delivery systems for antigens, and they can carefully be customized towards desired immune profiles by combining them with immunostimulators and optimizing their composition, physicochemical properties and antigen-loading mode. Immunostimulators represent highly diverse classes of molecules, e.g., lipids, nucleic acids, proteins and peptides, and they are ligands for pattern-recognition receptors (PRRs), which are differentially expressed on APC subsets. Different formulation strategies might thus be required for incorporation of immunostimulators and antigens, respectively, into liposomes, and the choice of immunostimulator should ideally be based on knowledge regarding the specific PRR

  7. Genetics and complementation of Haemophilus influenzae mutants deficient in adenosine 5'-triphosphate-dependent nuclease.

    PubMed Central

    Kooistra, J; Small, G D; Setlow, J K; Shapanka, R

    1976-01-01

    Eight different mutations in Haemophilus influenzae leading to deficiency in adenosine 5'-triphosphate (ATP)-dependent nuclease have been investigated in strains in which the mutations of the originally mutagenized strains have been transferred into the wild type. Sensitivity to mitomycin C and deoxycholate and complementation between extracts and deoxyribonucleic acid (DNA)-dependent ATPase activity have been measured. Genetic crosses have provided information on the relative position of the mutations on the genome. There are three complementation groups, corresponding to three genetic groups. The strains most sensitive to mitomycin and deoxycholate, derived from mutants originally selected on the basis of sensitivity to mitomycin C or methyl methanesulfonate, are in one group. Apparently all these sensitive strains lack DNA-dependent ATPase activity, as does a strain intermediate in sensitivity to deoxycholate, which is the sole representative of another group. There are four strains that are relatively resistant to deoxycholate and mitomycin C, and all of these contain the ATPase activity. Three of these are in the same genetic and complementation group, whereas the other incongruously belongs in the same group as the sensitive strains. It is postulated that there are three cistrons in H. influenzae that code for the three known subunits of the ATP-dependent nuclease. PMID:177397

  8. Super short membrane-active lipopeptides inhibiting the entry of influenza A virus.

    PubMed

    Wu, Wenjiao; Wang, Jingyu; Lin, Dongguo; Chen, Linqing; Xie, Xiangkun; Shen, Xintian; Yang, Qingqing; Wu, Qiuyi; Yang, Jie; He, Jian; Liu, Shuwen

    2015-10-01

    Influenza A viruses (IAV) are significant pathogens that result in millions of human infections and impose a substantial health and economic burdens worldwide. Due to the limited anti-influenza A therapeutics available and the emergence of drug resistant viral strains, it is imperative to develop potent anti-IAV agents with different mode of action. In this study, by applying a pseudovirus based screening approach, two super short membrane-active lipopeptides of C12-KKWK and C12-OOWO were identified as effective anti-IAV agents with IC50 value of 7.30±1.57 and 8.48±0.74 mg/L against A/Puerto Rico/8/34 strain, and 6.14±1.45 and 7.22±0.67 mg/L against A/Aichi/2/68 strain, respectively. The mechanism study indicated that the anti-IAV activity of these peptides would result from the inhibition of virus entry by interacting with HA2 subunit of hemagglutinin (HA). Thus, these peptides may have potentials as lead peptides for the development of new anti-IAV therapeutics to block the entry of virus into host cells. PMID:26092189

  9. New Insight into Metal Ion-Driven Catalysis of Nucleic Acids by Influenza PA-Nter

    PubMed Central

    Kotlarek, Daria; Worch, Remigiusz

    2016-01-01

    PA subunit of influenza RNA-dependent RNA polymerase deserves constantly increasing attention due to its essential role in influenza life cycle. N-terminal domain of PA (PA-Nter) harbors endonuclease activity, which is indispensable in viral transcription and replication. Interestingly, existing literature reports on in vitro ion preferences of the enzyme are contradictory. Some show PA-Nter activity exclusively with Mn2+, whereas others report Mg2+ as a natural cofactor. To clarify it, we performed a series of experiments with varied ion concentrations and substrate type. We observed cleavage in the presence of both ions, with a slight preference for manganese, however PA-Nter activity highly depended on the amount of residual, co-purified ions. Furthermore, to quantify cleavage reaction rate, we applied fluorescence cross-correlation spectroscopy (FCCS), providing highly sensitive and real-time monitoring of single molecules. Using nanomolar ssDNA in the regime of enzyme excess, we estimated the maximum reaction rate at 0.81± 0.38 and 1.38± 0.34 nM/min for Mg2+ and Mn2+, respectively. However, our calculations of PA-Nter ion occupancy, based on thermodynamic data, suggest Mg2+ to be a canonical metal in PA-Nter processing of RNA in vivo. Presented studies constitute a step toward better understanding of PA-Nter ion-dependent activity, which will possibly contribute to new successful inhibitor design in the future. PMID:27300442

  10. Production of Influenza Virus HA1 Harboring Native-Like Epitopes by Pichia pastoris.

    PubMed

    Lin, Qingshan; Yang, Kunyu; He, Fangping; Jiang, Jie; Li, Tingting; Chen, Zhenqin; Li, Rui; Chen, Yixin; Li, Shaowei; Zhao, Qinjian; Xia, Ningshao

    2016-08-01

    The outbreak of the H5N1 highly pathogenic avian influenza which exhibits high variation had brought a serious threat to the safety of humanity. To overcome this high variation, hemagglutinin-based recombinant subunit vaccine with rational design has been considered as a substitute for traditional virion-based vaccine development. Here, we expressed HA1 part of the hemagglutinin protein using the Pichia pastoris expression system and attained a high yield of about 120 mg/L through the use of fed-batch scalable fermentation. HA1 protein in the culture supernatant was purified using two-step ion-exchange chromatography. The resultant HA1 protein was homogeneous in solution in a glycosylated form, as confirmed by endoglycosidase H treatment. Sedimentation velocity tests, silver staining of protein gels, and immunoblotting were used for verification. The native HA1 reacted well with conformational, cross-genotype, neutralizing monoclonal antibodies, whereas a loss of binding activity was noted with the denatured HA1 form. Moreover, the murine anti-HA1 serum exhibited a virus-capture capability in the hemagglutination inhibition assay, which suggests that HA1 harbors native-like epitopes. In conclusion, soluble HA1 was efficiently expressed and purified in this study. The functional glycosylated protein will be an alternative for the development of recombinant protein-based influenza vaccine. PMID:27040529

  11. Influenza leaves a TRAIL to pulmonary edema.

    PubMed

    Brauer, Rena; Chen, Peter

    2016-04-01

    Influenza infection can cause acute respiratory distress syndrome (ARDS), leading to poor disease outcome with high mortality. One of the driving features in the pathogenesis of ARDS is the accumulation of fluid in the alveoli, which causes severe pulmonary edema and impaired oxygen uptake. In this issue of the JCI, Peteranderl and colleagues define a paracrine communication between macrophages and type II alveolar epithelial cells during influenza infection where IFNα induces macrophage secretion of TRAIL that causes endocytosis of Na,K-ATPase by the alveolar epithelium. This reduction of Na,K-ATPase expression decreases alveolar fluid clearance, which in turn leads to pulmonary edema. Inhibition of the TRAIL signaling pathway has been shown to improve lung injury after influenza infection, and future studies will be needed to determine if blocking this pathway is a viable option in the treatment of ARDS. PMID:26999598

  12. Parent preferences for pediatric influenza vaccine attributes.

    PubMed

    Flood, Emuella M; Ryan, Kellie J; Rousculp, Matthew D; Beusterien, Kathleen M; Divino, Victoria M; Block, Stan L; Hall, Matthew C; Mahadevia, Parthiv J

    2011-04-01

    Influenza vaccine is available as an intramuscular injection or an intranasal spray for eligible children. This study was conducted to examine parents' preferences for influenza vaccine attributes and the attributes' relative importance regarding the vaccination of their children. A quantitative Web survey was administered to 500 parents of children aged 2 to 12 years. The survey included general preference questions and conjoint (trade-off) questions. Parents most frequently selected efficacy, risk of temporary side effects, and physician recommendation as important vaccine attributes from a provided list (92%, 75%, and 59%, respectively). For attributes selected as important, parents rated the importance of the attribute; the highest mean importance ratings were given to efficacy, presence of mercury-containing preservative, and physician recommendation.The highest relative importance ratings in the conjoint section were given to efficacy and presence of mercury-containing preservative. Parental education on influenza vaccine efficacy and safety may help to improve pediatric vaccination rates. PMID:21196417

  13. Pandemic influenza: implications for occupational medicine

    PubMed Central

    Journeay, W Shane; Burnstein, Matthew D

    2009-01-01

    This article reviews the biological and occupational medicine literature related to H5N1 pandemic influenza and its impact on infection control, cost and business continuity in settings outside the health care community. The literature on H5N1 biology is reviewed including the treatment and infection control mechanisms as they pertain to occupational medicine. Planning activity for the potential arrival of pandemic avian influenza is growing rapidly. Much has been published on the molecular biology of H5N1 but there remains a paucity of literature on the occupational medicine impacts to organizations. This review summarizes some of the basic science surrounding H5N1 influenza and raises some key concerns in pandemic planning for the occupational medicine professional. Workplaces other than health care settings will be impacted greatly by an H5N1 pandemic and the occupational physician will play an essential role in corporate preparation, response, and business continuity strategies. PMID:19549302

  14. Recent zoonoses caused by influenza A viruses.

    PubMed

    Alexander, D J; Brown, I H

    2000-04-01

    Influenza is a highly contagious, acute illness which has afflicted humans and animals since ancient times. Influenza viruses are part of the Orthomyxoviridae family and are grouped into types A, B and C according to antigenic characteristics of the core proteins. Influenza A viruses infect a large variety of animal species, including humans, pigs, horses, sea mammals and birds, occasionally producing devastating pandemics in humans, such as in 1918, when over twenty million deaths occurred world-wide. The two surface glycoproteins of the virus, haemagglutinin (HA) and neuraminidase (NA), are the most important antigens for inducing protective immunity in the host and therefore show the greatest variation. For influenza A viruses, fifteen antigenically distinct HA subtypes and nine NA subtypes are recognised at present; a virus possesses one HA and one NA subtype, apparently in any combination. Although viruses of relatively few subtype combinations have been isolated from mammalian species, all subtypes, in most combinations, have been isolated from birds. In the 20th Century, the sudden emergence of antigenically different strains in humans, termed antigenic shift, has occurred on four occasions, as follows, in 1918 (H1N1), 1957 (H2N2), 1968 (H3N2) and 1977 (H1N1), each resulting in a pandemic. Frequent epidemics have occurred between the pandemics as a result of gradual antigenic change in the prevalent virus, termed antigenic drift. Currently, epidemics occur throughout the world in the human population due to infection with influenza A viruses of subtypes H1N1 and H3N2 or with influenza B virus. The impact of these epidemics is most effectively measured by monitoring excess mortality due to pneumonia and influenza. Phylogenetic studies suggest that aquatic birds could be the source of all influenza A viruses in other species. Human pandemic strains are thought to have emerged through one of the following three mechanisms: genetic reassortment (occurring as a

  15. Innate immune evasion strategies of influenza viruses

    PubMed Central

    Hale, Benjamin G; Albrecht, Randy A; García-Sastre, Adolfo

    2010-01-01

    Influenza viruses are globally important human respiratory pathogens. These viruses cause seasonal epidemics and occasional worldwide pandemics, both of which can vary significantly in disease severity. The virulence of a particular influenza virus strain is partly determined by its success in circumventing the host immune response. This article briefly reviews the innate mechanisms that host cells have evolved to resist virus infection, and outlines the plethora of strategies that influenza viruses have developed in order to counteract such powerful defences. The molecular details of this virus–host interplay are summarized, and the ways in which research in this area is being applied to the rational design of protective vaccines and novel antivirals are discussed. PMID:20020828

  16. The light subunit of system bo,+ is fully functional in the absence of the heavy subunit

    PubMed Central

    Reig, Núria; Chillarón, Josep; Bartoccioni, Paola; Fernández, Esperanza; Bendahan, Annie; Zorzano, Antonio; Kanner, Baruch; Palacín, Manuel; Bertran, Joan

    2002-01-01

    The heteromeric amino acid transporters are composed of a type II glycoprotein and a non-glycosylated polytopic membrane protein. System bo,+ exchanges dibasic for neutral amino acids. It is composed of rBAT and bo,+AT, the latter being the polytopic membrane subunit. Mutations in either of them cause malfunction of the system, leading to cystinuria. bo,+AT-reconstituted systems from HeLa or MDCK cells catalysed transport of arginine that was totally dependent on the presence of one of the bo,+ substrates inside the liposomes. rBAT was essential for the cell surface expression of bo,+AT, but it was not required for reconstituted bo,+AT transport activity. No system bo,+ transport was detected in liposomes derived from cells expressing rBAT alone. The reconstituted bo,+AT showed kinetic asymmetry. Expressing the cystinuria-specific mutant A354T of bo,+AT in HeLa cells together with rBAT resulted in defective arginine uptake in whole cells, which was paralleled by the reconstituted bo,+AT activity. Thus, subunit bo,+AT by itself is sufficient to catalyse transmembrane amino acid exchange. The polytopic subunits may also be the catalytic part in other heteromeric transporters. PMID:12234930

  17. Epitopes from two soybean glycinin subunits antigenic in pigs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: Glycinin is a seed storage protein in soybean (Glycine max) that is allergenic in pigs. Glycinin is a hexamer composed of subunits consisting of a basic and acidic portion joined by disulfide bridges. There are 5 glycinin subunits designated Gy1-Gy5. Results: Twenty seven out of 30 pi...

  18. The Development and Institutionalization of Subunit Power in Organizations.

    ERIC Educational Resources Information Center

    Boeker, Warren

    1989-01-01

    Examines the effects of founding events on the evolution of subunit importance in the semiconductor industry from 1958 to 1985. Distributions of power and subunit importance represent not only influences of current conditions, but also vestiges of earlier events, including the institution's founding. Includes 55 references. (MLH)

  19. Proteopedia Entry: The Large Ribosomal Subunit of "Haloarcula Marismortui"

    ERIC Educational Resources Information Center

    Decatur, Wayne A.

    2010-01-01

    This article presents a "Proteopedia" page that shows the refined version of the structure of the "Haloarcula" large ribosomal subunit as solved by the laboratories of Thomas Steitz and Peter Moore. The landmark structure is of great impact as it is the first atomic-resolution structure of the highly conserved ribosomal subunit which harbors…

  20. Geranyl diphosphate synthase large subunit, and methods of use

    DOEpatents

    Croteau, Rodney B.; Burke, Charles C.; Wildung, Mark R.

    2001-10-16

    A cDNA encoding geranyl diphosphate synthase large subunit from peppermint has been isolated and sequenced, and the corresponding amino acid sequence has been determined. Replicable recombinant cloning vehicles are provided which code for geranyl diphosphate synthase large subunit). In another aspect, modified host cells are provided that have been transformed, transfected, infected and/or injected with a recombinant cloning vehicle and/or DNA sequence encoding geranyl diphosphate synthase large subunit. In yet another aspect, the present invention provides isolated, recombinant geranyl diphosphate synthase protein comprising an isolated, recombinant geranyl diphosphate synthase large subunit protein and an isolated, recombinant geranyl diphosphate synthase small subunit protein. Thus, systems and methods are provided for the recombinant expression of geranyl diphosphate synthase.

  1. Modulation of Kv4.3 current by accessory subunits.

    PubMed

    Deschênes, Isabelle; Tomaselli, Gordon F

    2002-09-25

    Kv4.3 encodes the pore-forming subunit of the cardiac transient outward potassium current (I(to)). hKv4.3-encoded current does not fully replicate cardiac I(to), suggesting a functionally significant role for accessory subunits. KChIP2 associates with Kv4.3 and modifies hKv4.3-encoded currents but does not replicate native I(to). We examined the effect of several ancillary subunits expressed in the heart on hKv4.3-encoded currents. Remarkably, the ancillary subunits Kvbeta(3), minK, MiRP-1, the Na channel beta(1) and KChIP2 increased the density and modified the gating of hKv4.3 current. hKv4.3 promiscuously assembles with ancillary subunits in vitro, functionally modifying the encoded currents; however, the physiological significance is uncertain. PMID:12297301

  2. Antimicrobial Resistance in Haemophilus influenzae

    PubMed Central

    Tristram, Stephen; Jacobs, Michael R.; Appelbaum, Peter C.

    2007-01-01

    Haemophilus influenzae is a major community-acquired pathogen causing significant morbidity and mortality worldwide. Meningitis and bacteremia due to type b strains occur in areas where the protein-conjugated type b vaccine is not in use, whereas nontypeable strains are major causes of otitis media, sinusitis, acute exacerbations of chronic bronchitis, and pneumonia. Antibiotic resistance in this organism is more diverse and widespread than is commonly appreciated. Intrinsic efflux resistance mechanisms limit the activity of the macrolides, azalides, and ketolides. β-Lactamase production is highly prevalent worldwide and is associated with resistance to ampicillin and amoxicillin. Strains with alterations in penicillin binding proteins, particularly PBP3 (β-lactamase negative ampicillin resistant and β-lactamase positive amoxicillin-clavulanate resistant), are increasing in prevalence, particularly in Japan, with increasing resistance to ampicillin, amoxicillin, amoxicillin-clavulanate, and many cephalosporins, limiting the efficacy of expanded-spectrum cephalosporins against meningitis and of many oral cephalosporins against other diseases. Most strains remain susceptible to the carbapenems, which are not affected by penicillin binding protein changes, and the quinolones. The activity of many oral agents is limited by pharmacokinetics achieved with administration by this route, and the susceptibility of isolates based on pharmacokinetic and pharmacodynamic parameters is reviewed. PMID:17428889

  3. Future directions for the European influenza reference laboratory network in influenza surveillance.

    PubMed

    Goddard, N; Rebelo-de-Andrade, H; Meijer, A; McCauley, J; Daniels, R; Zambon, M

    2015-01-01

    By defining strategic objectives for the network of influenza laboratories that have national influenza centre status or national function within European Union Member States, Iceland and Norway, it is possible to align their priorities in undertaking virological surveillance of influenza. This will help maintain and develop the network to meet and adapt to new challenges over the next 3-5 years and underpin a longer-term strategy over 5-10 years. We analysed the key activities undertaken by influenza reference laboratories in Europe and categorised them into a framework of four key strategic objectives areas: enhancing laboratory capability, ensuring laboratory capacity, providing emergency response and translating laboratory data into information for public health action. We make recommendations on the priority areas for future development. PMID:26250071

  4. Temporal Patterns of Influenza A and B in Tropical and Temperate Countries: What Are the Lessons for Influenza Vaccination?

    PubMed Central

    Caini, Saverio; Andrade, Winston; Badur, Selim; Balmaseda, Angel; Barakat, Amal; Bella, Antonino; Bimohuen, Abderrahman; Brammer, Lynnette; Bresee, Joseph; Bruno, Alfredo; Castillo, Leticia; Ciblak, Meral A.; Clara, Alexey W.; Cohen, Cheryl; Cutter, Jeffery; Daouda, Coulibaly; de Lozano, Celina; De Mora, Domenica; Dorji, Kunzang; Emukule, Gideon O.; Fasce, Rodrigo A.; Feng, Luzhao; Ferreira de Almeida, Walquiria Aparecida; Guiomar, Raquel; Heraud, Jean-Michel; Holubka, Olha; Huang, Q. Sue; Kadjo, Herve A.; Kiyanbekova, Lyazzat; Kosasih, Herman; Kusznierz, Gabriela; Lara, Jenny; Li, Ming; Lopez, Liza; Mai Hoang, Phuong Vu; Pessanha Henriques, Cláudio Maierovitch; Matute, Maria Luisa; Mironenko, Alla; Moreno, Brechla; Mott, Joshua A.; Njouom, Richard; Nurhayati; Ospanova, Akerke; Owen, Rhonda; Pebody, Richard; Pennington, Kate; Puzelli, Simona; Quynh Le, Mai thi; Razanajatovo, Norosoa Harline; Rodrigues, Ana; Rudi, Juan Manuel; Tzer Pin Lin, Raymond; Venter, Marietjie; Vernet, Marie-Astrid; Wangchuk, Sonam; Yang, Juan; Yu, Hongjie; Zambon, Maria; Schellevis, François; Paget, John

    2016-01-01

    Introduction Determining the optimal time to vaccinate is important for influenza vaccination programmes. Here, we assessed the temporal characteristics of influenza epidemics in the Northern and Southern hemispheres and in the tropics, and discuss their implications for vaccination programmes. Methods This was a retrospective analysis of surveillance data between 2000 and 2014 from the Global Influenza B Study database. The seasonal peak of influenza was defined as the week with the most reported cases (overall, A, and B) in the season. The duration of seasonal activity was assessed using the maximum proportion of influenza cases during three consecutive months and the minimum number of months with ≥80% of cases in the season. We also assessed whether co-circulation of A and B virus types affected the duration of influenza epidemics. Results 212 influenza seasons and 571,907 cases were included from 30 countries. In tropical countries, the seasonal influenza activity lasted longer and the peaks of influenza A and B coincided less frequently than in temperate countries. Temporal characteristics of influenza epidemics were heterogeneous in the tropics, with distinct seasonal epidemics observed only in some countries. Seasons with co-circulation of influenza A and B were longer than influenza A seasons, especially in the tropics. Discussion Our findings show that influenza seasonality is less well defined in the tropics than in temperate regions. This has important implications for vaccination programmes in these countries. High-quality influenza surveillance systems are needed in the tropics to enable decisions about when to vaccinate. PMID:27031105

  5. 76 FR 78658 - Webinar Overview of the National Vaccine Advisory Committee Healthcare Personnel Influenza...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-19

    ... Influenza Vaccination Subgroup's Draft Report and Draft Recommendations for Achieving the Healthy People 2020 Annual Coverage Goals for Influenza Vaccination in Healthcare Personnel AGENCY: National Vaccine... of the National Vaccine Advisory Committee (NVAC), Healthcare Personnel Influenza...

  6. 76 FR 58466 - Request for Comments on World Health Organization Pandemic Influenza Preparedness Framework

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-21

    ... influenza preparedness via the Federal Register on September 14, 2010; 75 FR 55776-55777. The Department of... International Trade Administration Request for Comments on World Health Organization Pandemic Influenza... the World Health Organization Pandemic Influenza Preparedness Framework (...

  7. Representations of influenza and influenza-like illness in the community - a qualitative study

    PubMed Central

    2013-01-01

    Background There is little information regarding lay-people's representations of influenza and influenza-like illness in their day-to-day lives. An insight into these views may aid our understanding of community attitudes regarding official recommendations for its prevention. Methods This was a qualitative research. Semi-structured face-to-face interviews were conducted with 40 French participants from the community, and from five different locations. Questions elicited the participants' representations of onset of flu and influenza-like illness, as well as their views on what can/should be done to deal with symptoms and their personal experience with flu and flu-like symptoms. Results Thematic content analyses allowed us to identify five main themes: the presence of a clear continuum between influenza-like illness and flu; a description of flu as a very contagious disease; flu as being benign, except in "frail people", which the respondents never considered themselves to be; interruption of daily activities, which could be considered pathognomonic for influenza for most subjects; self-medication as the main current practice, and requests for healthcare mainly to confirm an auto-diagnosis. Conclusions There was a large homogeneity in the representation of flu. There was also a gap between people's representations (i.e., a continuum from having a "cold" to having "influenza") and scientific knowledge (i.e., a distinction between "true" influenza and influenza-like illnesses based on the existence of a confirmatory virological diagnosis). This gap raises issues for current campaigns for flu prevention, as these may not be congruent with the representation of flu being responsible for interrupting daily activities while also being seen as a non-severe disease, as well as the perception that flu is only a risk to "frail people" though no participants considered themselves to be "frail". PMID:23347756

  8. Elicitation of broadly neutralizing influenza antibodies in animals with previous influenza exposure.

    PubMed

    Wei, Chih-Jen; Yassine, Hadi M; McTamney, Patrick M; Gall, Jason G D; Whittle, James R R; Boyington, Jeffrey C; Nabel, Gary J

    2012-08-15

    The immune system responds to influenza infection by producing neutralizing antibodies to the viral surface protein, hemagglutinin (HA), which regularly changes its antigenic structure. Antibodies that target the highly conserved stem region of HA neutralize diverse influenza viruses and can be elicited through vaccination in animals and humans. Efforts to develop universal influenza vaccines have focused on strategies to elicit such antibodies; however, the concern has been raised that previous influenza immunity may abrogate the induction of such broadly protective antibodies. We show here that prime-boost immunization can induce broadly neutralizing antibody responses in influenza-immune mice and ferrets that were previously infected or vaccinated. HA stem-directed antibodies were elicited in mice primed with a DNA vaccine and boosted with inactivated vaccine from H1N1 A/New Caledonia/20/1999 (1999 NC) HA regardless of preexposure. Similarly, gene-based vaccination with replication-defective adenovirus 28 (rAd28) and 5 (rAd5) vectors encoding 1999 NC HA elicited stem-directed neutralizing antibodies and conferred protection against unmatched 1934 and 2007 H1N1 virus challenge in influenza-immune ferrets. Indeed, previous exposure to certain strains could enhance immunogenicity: The strongest HA stem-directed immune response was observed in ferrets previously infected with a divergent 1934 H1N1 virus. These findings suggest that broadly neutralizing antibodies against the conserved stem region of HA can be elicited through vaccination despite previous influenza exposure, which supports the feasibility of developing stem-directed universal influenza vaccines for humans. PMID:22896678

  9. Live attenuated influenza viruses produced in a suspension process with avian AGE1.CR.pIX cells

    PubMed Central

    2012-01-01

    Background Current influenza vaccines are trivalent or quadrivalent inactivated split or subunit vaccines administered intramuscularly, or live attenuated influenza vaccines (LAIV) adapted to replicate at temperatures below body temperature and administered intranasally. Both vaccines are considered safe and efficient, but due to differences in specific properties may complement each other to ensure reliable vaccine coverage. By now, licensed LAIV are produced in embryonated chicken eggs. In the near future influenza vaccines for human use will also be available from adherent MDCK or Vero cell cultures, but a scalable suspension process may facilitate production and supply with vaccines. Results We evaluated the production of cold-adapted human influenza virus strains in the duck suspension cell line AGE1.CR.pIX using a chemically-defined medium. One cold-adapted A (H1N1) and one cold-adapted B virus strain was tested, as well as the reference strain A/PR/8/34 (H1N1). It is shown that a medium exchange is not required for infection and that maximum virus titers are obtained for 1 × 10-6 trypsin units per cell. 1 L bioreactor cultivations showed that 4 × 106 cells/mL can be infected without a cell density effect achieving titers of 1 × 108 virions/mL after 24 h. Conclusions Overall, this study demonstrates that AGE1.CR.pIX cells support replication of LAIV strains in a chemically-defined medium using a simple process without medium exchanges. Moreover, the process is fast with peak titers obtained 24 h post infection and easily scalable to industrial volumes as neither microcarriers nor medium replacements are required. PMID:23110398

  10. Method for the detection of a polypeptide subunit in the presence of a quaternary protein containing the subunit

    SciTech Connect

    Wands, J.R.; Ozturk, M.; Bellet, D.

    1990-06-12

    This patent describes a method for the determination of a free protein subunit of hCG in a sample containing intact quaternary hCG. It comprises: contacting the sample with a first monoclonal antibody which is bound to a carrier, wherein the first monoclonal antibody binds epitopic determinants bindable only on the free protein subunit; incubating the components for a period of time and under conditions sufficient to form an immune complex between the free protein subunit, the first monoclonal antibody, and the carrier; separating the carrier from the sample; adding to the carrier a detectably labeled second monoclonal antibody, wherein the second monoclonal antibody binds epitopic determinants bindable on both the free protein subunit and the intact quaternary hCG; separating the carrier from the liquid phase; and determining the detectably labeled second monoclonal antibody in the carrier or in the liquid phase, which is a measure of the amount of the free protein subunit in the sample.

  11. Hemagglutinin and neuraminidase containing virus-like particles produced in HEK-293 suspension culture: An effective influenza vaccine candidate.

    PubMed

    Venereo-Sanchez, Alina; Gilbert, Renald; Simoneau, Melanie; Caron, Antoine; Chahal, Parminder; Chen, Wangxue; Ansorge, Sven; Li, Xuguang; Henry, Olivier; Kamen, Amine

    2016-06-17

    Virus-like particles (VLPs) constitute a promising alternative as influenza vaccine. They are non-replicative particles that mimic the morphology of native viruses which make them more immunogenic than classical subunit vaccines. In this study, we propose HEK-293 cells in suspension culture in serum-free medium as an efficient platform to produce large quantities of VLPs. For this purpose, a stable cell line expressing the main influenza viral antigens hemagglutinin (HA) and neuraminidase (NA) (subtype H1N1) under the regulation of a cumate inducible promoter was developed (293HA-NA cells). The production of VLPs was evaluated by transient transfection of plasmids encoding human immunodeficiency virus (HIV) Gag or M1 influenza matrix protein. To facilitate the monitoring of VLPs production, Gag was fused to the green fluorescence protein (GFP). The transient transfection of the gag containing plasmid in 293HA-NA cells increased the release of HA and NA seven times more than its counterpart transfected with the M1 encoding plasmid. Consequently, the production of HA-NA containing VLPs using Gag as scaffold was evaluated in a 3-L controlled stirred tank bioreactor. The VLPs secreted in the culture medium were recovered by ultracentrifugation on a sucrose cushion and ultrafiltered by tangential flow filtration. Transmission electron micrographs of final sample revealed the presence of particles with the average typical size (150-200nm) and morphology of HIV-1 immature particles. The concentration of the influenza glycoproteins on the Gag-VLPs was estimated by single radial immunodiffusion and hemagglutination assay for HA and by Dot-Blot for HA and NA. More significantly, intranasal immunization of mice with influenza Gag-VLPs induced strong antigen-specific mucosal and systemic antibody responses and provided full protection against a lethal intranasal challenge with the homologous virus strain. These data suggest that, with further optimization and characterization

  12. Gel-based chemical cross-linking analysis of 20S proteasome subunit-subunit interactions in breast cancer.

    PubMed

    Song, Hai; Xiong, Hua; Che, Jing; Xi, Qing-Song; Huang, Liu; Xiong, Hui-Hua; Zhang, Peng

    2016-08-01

    The ubiquitin-proteasome system plays a pivotal role in breast tumorigenesis by controlling transcription factors, thus promoting cell cycle growth, and degradation of tumor suppressor proteins. However, breast cancer patients have failed to benefit from proteasome inhibitor treatment partially due to proteasome heterogeneity, which is poorly understood in malignant breast neoplasm. Chemical crosslinking is an increasingly important tool for mapping protein three-dimensional structures and proteinprotein interactions. In the present study, two cross-linkers, bis (sulfosuccinimidyl) suberate (BS(3)) and its water-insoluble analog disuccinimidyl suberate (DSS), were used to map the subunit-subunit interactions in 20S proteasome core particle (CP) from MDA-MB-231 cells. Different types of gel electrophoresis technologies were used. In combination with chemical cross-linking and mass spectrometry, we applied these gel electrophoresis technologies to the study of the noncovalent interactions among 20S proteasome subunits. Firstly, the CP subunit isoforms were profiled. Subsequently, using native/SDSPAGE, it was observed that 0.5 mmol/L BS(3) was a relatively optimal cross-linking concentration for CP subunit-subunit interaction study. 2-DE analysis of the cross-linked CP revealed that α1 might preinteract with α2, and α3 might pre-interact with α4. Moreover, there were different subtypes of α1α2 and α3α4 due to proteasome heterogeneity. There was no significant difference in cross-linking pattern for CP subunits between BS(3) and DSS. Taken together, the gel-based characterization in combination with chemical cross-linking could serve as a tool for the study of subunit interactions within a multi-subunit protein complex. The heterogeneity of 20S proteasome subunit observed in breast cancer cells may provide some key information for proteasome inhibition strategy. PMID:27465334

  13. The 1918 influenza pandemic: Lessons for 2009 and the future

    PubMed Central

    Morens, David M.; Taubenberger, Jeffery K.; Harvey, Hillery A.; Memoli, Matthew J.

    2011-01-01

    The 1918 to 1919 H1N1 influenza pandemic is among the most deadly events in recorded human history, having killed an estimated 50 to 100 million persons. Recent H5N1 avian influenza epizootics associated with sporadic human fatalities have heightened concern that a new influenza pandemic, one at least as lethal as that of 1918, could be developing. In early 2009, a novel pandemic H1N1 influenza virus appeared, but it has not exhibited unusually high pathogenicity. Nevertheless, because this virus spreads globally, some scientists predict that mutations will increase its lethality. Therefore, to accurately predict, plan, and respond to current and future influenza pandemics, we must first better-understand the events and experiences of 1918. Although the entire genome of the 1918 influenza virus has been sequenced, many questions about the pandemic it caused remain unanswered. In this review, we discuss the origin of the 1918 pandemic influenza virus, the pandemic’s unusual epidemiologic features and the causes and demographic patterns of fatality, and how this information should impact our response to the current 2009 H1N1 pandemic and future pandemics. After 92 yrs of research, fundamental questions about influenza pandemics remain unanswered. Thus, we must remain vigilant and use the knowledge we have gained from 1918 and other influenza pandemics to direct targeted research and pandemic influenza preparedness planning, emphasizing prevention, containment, and treatment. PMID:20048675

  14. Antigenic Distance Measurements for Seasonal Influenza Vaccine Selection

    PubMed Central

    Cai, Zhipeng; Zhang, Tong; Wan, Xiu-Feng

    2011-01-01

    Influenza vaccination is one of the major options to counteract the effects of influenza diseases. Selection of an effective vaccine strain is the key to the success of an effective vaccination program since vaccine protection can only be achieved when the selected influenza vaccine strain matches the antigenic variants causing future outbreaks. Identification of an antigenic variant is the first step to determine whether vaccine strain needs to be updated. Antigenic distance derived from immunological assays, such as hemagglutination inhibition, is commonly used to measure the antigenic closeness between circulating strains and the current influenza vaccine strain. Thus, consensus on an explicit and robust antigenic distance measurement is critical in influenza surveillance. Based on the current seasonal influenza surveillance procedure, we propose and compare three antigenic distance measurements, including Average antigenic distance (A-distance), Mutual antigenic distance (M-distance), and Largest antigenic distance (L-distance). With the assistance of influenza antigenic cartography, our simulation results demonstrated that M-distance is a robust influenza antigenic distance measurement. Experimental results on both simulation and seasonal influenza surveillance data demonstrate that M-distance can be effectively utilized in influenza vaccine strain selection. PMID:22063385

  15. A homogeneous biochemiluminescent assay for detection of influenza

    NASA Astrophysics Data System (ADS)

    Hui, Kwok Min; Li, Xiao Jing; Pan, Lu; Li, X. J.

    2015-05-01

    Current methods of rapid detection of influenza are based on detection of the nucleic acids or antigens of influenza viruses. Since influenza viruses constantly mutate leading to appearance of new strains or variants of viruses, these detection methods are susceptible to genetic changes in influenza viruses. Type A and B influenza viruses contain neuraminidase, an essential enzyme for virus replication which enables progeny influenza viruses leave the host cells to infect new cells. Here we describe an assay method, the homogeneous biochemiluminescent assay (HBA), for rapid detection of influenza by detecting viral neuraminidase activity. The assay mimics the light production process of a firefly: a viral neuraminidase specific substrate containing a luciferin moiety is cleaved in the presence of influenza virus to release luciferin, which becomes a substrate to firefly luciferase in a light production system. All reagents can be formulated in a single reaction mix so that the assay involves only one manual step, i.e., sample addition. Presence of Type A or B influenza virus in the sample leads to production of strong, stable and easily detectable light signal, which lasts for hours. Thus, this influenza virus assay is suitable for use in point-of-care settings.

  16. [Detection of local influenza outbreaks and role of virological diagnostics].

    PubMed

    Schweiger, B; Buda, S

    2013-01-01

    For many years, the Working Group on Influenza (AGI) has been the most important influenza surveillance system in Germany. An average sample of the population is covered by both syndromic and virological surveillance, which provides timely data regarding the onset and course of the influenza wave as well as its burden of disease. However, smaller influenza outbreaks cannot be detected by the AGI sentinel system. This is achieved by the information reported by the mandatory notification system (Protection Against Infection Act, IfSG), which serves as the second pillar of the national influenza surveillance. Approaches to recognize such outbreaks are based either on reported influenza virus detection and subsequent investigations by local health authorities or by notification of an accumulation of respiratory diseases or nosocomial infections and subsequent laboratory investigations. In this context, virological diagnostics plays an essential role. This has been true particularly for the early phase of the 2009 pandemic, but generally timely diagnostics is essential for the identification of outbreaks. Regarding potential future outbreaks, it is also important to keep an eye on animal influenza viruses that have repeatedly infected humans. This mainly concerns avian influenza viruses of the subtypes H5, H7, and H9 as well as porcine influenza viruses for which a specific PCR has been established at the National Influenza Reference Centre. An increased incidence of respiratory infections, both during and outside the season, should always encourage virological laboratory diagnostics to be performed as a prerequisite of further extensive investigations and an optimal outbreak management. PMID:23275953

  17. Stargazin is an AMPA receptor auxiliary subunit.

    PubMed

    Vandenberghe, Wim; Nicoll, Roger A; Bredt, David S

    2005-01-11

    AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptors mediate fast excitatory synaptic transmission in brain and underlie aspects of synaptic plasticity. Numerous AMPA receptor-binding proteins have been implicated in AMPA receptor trafficking and anchoring. However, the relative contributions of these proteins to the composition of native AMPA receptor complexes in brain remain uncertain. Here, we use blue native gel electrophoresis to analyze the composition of native AMPA receptor complexes in cerebellar extracts. We identify two receptor populations: a functional form that contains the transmembrane AMPA receptor-regulatory protein stargazin and an apo-form that lacks stargazin. Limited proteolysis confirms assembly of stargazin with a large proportion of native AMPA receptors. In contrast, other AMPA receptor-interacting proteins, such as synapse-associated protein 97, glutamate receptor-interacting protein 1, protein kinase Calpha binding protein, N-ethylmaleimide-sensitive fusion protein, AP2, and protein 4.1N, do not show significant association with AMPA receptor complexes on native gels. These data identify stargazin as an auxiliary subunit for a neurotransmitter-gated ion channel. PMID:15630087

  18. Replication and transcription activities of ribonucleoprotein complexes reconstituted from avian H5N1, H1N1pdm09 and H3N2 influenza A viruses.

    PubMed

    Ngai, Karry L K; Chan, Martin C W; Chan, Paul K S

    2013-01-01

    Avian influenza viruses pose a serious pandemic threat to humans. Better knowledge on cross-species adaptation is important. This study examined the replication and transcription efficiency of ribonucleoprotein complexes reconstituted by plasmid co-transfection between H5N1, H1N1pdm09 and H3N2 influenza A viruses, and to identify mutations in the RNA polymerase subunit that affect human adaptation. Viral RNA polymerase subunits PB1, PB2, PA and NP derived from influenza viruses were co-expressed with pPolI-vNP-Luc in human cells, and with its function evaluated by luciferase reporter assay. A quantitative RT-PCR was used to measure vRNA, cRNA, and mRNA levels for assessing the replication and transcription efficiency. Mutations in polymerase subunit were created to identify signature of increased human adaptability. H5N1 ribonucleoprotein complexes incorporated with PB2 derived from H1N1pdm09 and H3N2 viruses increased the polymerase activity in human cells. Furthermore, single amino acid substitutions at PB2 of H5N1 could affect polymerase activity in a temperature-dependent manner. By using a highly sensitive quantitative reverse transcription-polymerase chain reaction, an obvious enhancement in replication and transcription activities of ribonucleoproteins was observed by the introduction of lysine at residue 627 in the H5N1 PB2 subunit. Although less strongly in polymerase activity, E158G mutation appeared to alter the accumulation of H5N1 RNA levels in a temperature-dependent manner, suggesting a temperature-dependent mechanism in regulating transcription and replication exists. H5N1 viruses can adapt to humans either by acquisition of PB2 from circulating human-adapted viruses through reassortment, or by mutations at critical sites in PB2. This information may help to predict the pandemic potential of newly emerged influenza strains, and provide a scientific basis for stepping up surveillance measures and vaccine production. PMID:23750226

  19. Autocatalytic processing of m-AAA protease subunits in mitochondria.

    PubMed

    Koppen, Mirko; Bonn, Florian; Ehses, Sarah; Langer, Thomas

    2009-10-01

    m-AAA proteases are ATP-dependent proteolytic machines in the inner membrane of mitochondria which are crucial for the maintenance of mitochondrial activities. Conserved nuclear-encoded subunits, termed paraplegin, Afg3l1, and Afg3l2, form various isoenzymes differing in their subunit composition in mammalian mitochondria. Mutations in different m-AAA protease subunits are associated with distinct neuronal disorders in human. However, the biogenesis of m-AAA protease complexes or of individual subunits is only poorly understood. Here, we have examined the processing of nuclear-encoded m-AAA protease subunits upon import into mitochondria and demonstrate autocatalytic processing of Afg3l1 and Afg3l2. The mitochondrial processing peptidase MPP generates an intermediate form of Afg3l2 that is matured autocatalytically. Afg3l1 or Afg3l2 are also required for maturation of newly imported paraplegin subunits after their cleavage by MPP. Our results establish that mammalian m-AAA proteases can act as processing enzymes in vivo and reveal overlapping activities of Afg3l1 and Afg3l2. These findings might be of relevance for the pathogenesis of neurodegenerative disorders associated with mutations in different m-AAA protease subunits. PMID:19656850

  20. Both subunits of ADP-glucose pyrophosphorylase are regulatory.

    PubMed

    Cross, Joanna M; Clancy, Maureen; Shaw, Janine R; Greene, Thomas W; Schmidt, Robert R; Okita, Thomas W; Hannah, L Curtis

    2004-05-01

    The allosteric enzyme ADP-Glc pyrophosphorylase (AGPase) catalyzes the synthesis of ADP-Glc, a rate-limiting step in starch synthesis. Plant AGPases are heterotetramers, most of which are activated by 3-phosphoglyceric acid (3-PGA) and inhibited by phosphate. The objectives of these studies were to test a hypothesis concerning the relative roles of the two subunits and to identify regions in the subunits important in allosteric regulation. We exploited an Escherichia coli expression system and mosaic AGPases composed of potato (Solanum tuberosum) tuber and maize (Zea mays) endosperm subunit fragments to pursue this objective. Whereas potato and maize subunits have long been separated by speciation and evolution, they are sufficiently similar to form active mosaic enzymes. Potato tuber and maize endosperm AGPases exhibit radically different allosteric properties. Hence, comparing the kinetic properties of the mosaics to those of the maize endosperm and potato tuber AGPases has enabled us to identify regions important in regulation. The data herein conclusively show that both subunits are involved in the allosteric regulation of AGPase. Alterations in the small subunit condition drastically different allosteric properties. In addition, extent of 3-PGA activation and extent of 3-PGA affinity were found to be separate entities, mapping to different regions in both subunits. PMID:15122037

  1. RNA polymerase II subunit composition, stoichiometry, and phosphorylation.

    PubMed Central

    Kolodziej, P A; Woychik, N; Liao, S M; Young, R A

    1990-01-01

    RNA polymerase II subunit composition, stoichiometry, and phosphorylation were investigated in Saccharomyces cerevisiae by attaching an epitope coding sequence to a well-characterized RNA polymerase II subunit gene (RPB3) and by immunoprecipitating the product of this gene with its associated polypeptides. The immunopurified enzyme catalyzed alpha-amanitin-sensitive RNA synthesis in vitro. The 10 polypeptides that immunoprecipitated were identical in size and number to those previously described for RNA polymerase II purified by conventional column chromatography. The relative stoichiometry of the subunits was deduced from knowledge of the sequence of the subunits and from the extent of labeling with [35S]methionine. Immunoprecipitation from 32P-labeled cell extracts revealed that three of the subunits, RPB1, RPB2, and RPB6, are phosphorylated in vivo. Phosphorylated and unphosphorylated forms of RPB1 could be distinguished; approximately half of the RNA polymerase II molecules contained a phosphorylated RPB1 subunit. These results more precisely define the subunit composition and phosphorylation of a eucaryotic RNA polymerase II enzyme. Images PMID:2183013

  2. Prokaryotic and eukaryotic RNA polymerases have homologous core subunits.

    PubMed Central

    Sweetser, D; Nonet, M; Young, R A

    1987-01-01

    Eukaryotic RNA polymerases are complex aggregates whose component subunits are functionally ill-defined. The gene that encodes the 140,000-dalton subunit of Saccharomyces cerevisiae RNA polymerase II was isolated and studied in detail to obtain clues to the protein's function. This gene, RPB2, exists in a single copy in the haploid genome. Disruption of the gene is lethal to the yeast cell. RPB2 encodes a protein of 138,750 daltons, which contains sequences implicated in binding purine nucleotides and zinc ions and exhibits striking sequence homology with the beta subunit of Escherichia coli RNA polymerase. These observations suggest that the yeast and the E. coli subunit have similar roles in RNA synthesis, as the beta subunit contains binding sites for nucleotide substrates and a portion of the catalytic site for RNA synthesis. The subunit homologies reported here, and those observed previously with the largest RNA polymerase subunit, indicate that components of the prokaryotic RNA polymerase "core" enzyme have counterparts in eukaryotic RNA polymerases. PMID:3547406

  3. [Influenza surveillance in five consecutive seasons during post pandemic period: results from National Influenza Center, Turkey].

    PubMed

    Altaş, Ayşe Başak; Bayrakdar, Fatma; Korukluoğlu, Gülay

    2016-07-01

    Influenza surveillance provides data about the characteristics of influenza activity, types, sub-types and antigenic properties of the influenza viruses in circulation in a region. Surveillance also provides for the preparation against potential influenza pandemics with the identification of the genetic properties of viruses and the mutant strains that could pose a threat. In this study, data in the scope of national influenza surveillance carried out by National Influenza Center, Turkey for five consecutive influenza seasons between 2010-2015, following the A(H1N1)pdm09 virus pandemic, have been presented and evaluated. A total of 15.149 respiratory samples, including 8.894 sentinel and 6.255 non-sentinel specimens, during 2010-2015 influenza seasons, within the periods between September and May, were evaluated in our center. All samples were tested using real-time reverse transcriptase PCR (rRT-PCR) for the presence of influenza virus types and subtypes. Within the sentinel influenza surveillance, the samples that were detected negative for influenza viruses, have also been tested for the other respiratory viruses (respiratory syncytial virus, rhinoviruses, paramyxoviruses, coronaviruses) using the same technique. Further analysis, including virus isolation by cell culture inoculation and antigenic characterization by hemagglutination inhibiton test were performed for the samples found positive for influenza A and B viruses. Selected representative virus isolates have been sent to WHO reference laboratory for the sequence analysis. In the study, influenza virus positivity rates detected for all of the samples (sentinel+non-sentinel) were as follows; 34% (779/2316) in 2010-11 season; 25% (388/1554) in 2011-12; 20% (696/3541) in 2012-13; 23% (615/2678) in 2013-14; and 26% (1332/5060) in 2014-15. When all the samples were considered for influenza A and B viruses, the positivity rates for the seasons of 2010-11; 2011-12; 2012-13; 2013-14; 2014-15 were determined as

  4. Issuance of Patient Reminders for Influenza Vaccination by US-Based Primary Care Physicians During the First Year of Universal Influenza Vaccination Recommendations

    PubMed Central

    Harris, Katherine M.

    2014-01-01

    To estimate the number of physician-reported influenza vaccination reminders during the 2010–2011 influenza season, the first influenza season after universal vaccination recommendations for influenza were introduced, we interviewed 493 members of the Physicians Consulting Network. Patient vaccination reminders are a highly effective means of increasing influenza vaccination; nonetheless, only one quarter of the primary care physicians interviewed issued influenza vaccination reminders during the first year of universal vaccination recommendations, highlighting the need to improve office-based promotion of influenza vaccination. PMID:24825233

  5. Virological analysis of fatal influenza cases in the United Kingdom during the early wave of influenza in winter 2010/11.

    PubMed

    Ellis, J; Galiano, M; Pebody, R; Lackenby, A; Thompson, C; Bermingham, A; McLean, E; Zhao, H; Bolotin, S; Dar, O; Watson, J M; Zambon, M

    2011-01-01

    The 2010/11 winter influenza season is underway in the United Kingdom, with co-circulation of influenza A(H1N1)2009 (antigenically similar to the current 2010/11 vaccine strain), influenza B (mainly B/Victoria/2/87 lineage, similar to the 2010/11 vaccine strain) and a few sporadic influenza A(H3N2) viruses. Clinical influenza activity has been increasing. Severe illness, resulting in hospitalisation and deaths, has occurred in children and young adults and has predominantly been associated with influenza A(H1N1)2009, but also influenza B viruses. PMID:21223836

  6. Haemophilus influenzae type b (Hib) Vaccine

    MedlinePlus

    ... influenzae type b (Hib) disease is a serious disease caused by bacteria. It usually affects children under 5 years old. It can also affect adults with certain medical conditions.Your child can get Hib disease by being around other children or adults who ...

  7. Pathobiology of avian influenza in domestic ducks

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Domestic ducks are an important source of food and income in many parts of the world. The susceptibility of domestic ducks to avian influenza (AI) viruses varies depending on many factors, including the species and the age of the ducks, the virus strain, and management practices. Although wild wat...

  8. Stability of influenza vaccine coated onto microneedles

    PubMed Central

    Choi, Hyo-Jick; Yoo, Dae-Goon; Bondy, Brian J.; Quan, Fu-Shi; Compans, Richard W.; Kang, Sang-Moo; Prausnitz, Mark R.

    2012-01-01

    A microneedle patch coated with vaccine simplifies vaccination by using a patch-based delivery method and targets vaccination to the skin for superior immunogenicity compared to intramuscular injection. Previous studies of microneedles have demonstrated effective vaccination using freshly prepared microneedles, but the issue of long-term vaccine stability has received only limited attention. Here, we studied the long-term stability of microneedles coated with whole inactivated influenza vaccine guided by the hypothesis that crystallization and phase separation of the microneedle coating matrix damages influenza vaccine coated onto microneedles. In vitro showed that the vaccine lost stability as measured by hemagglutination activity in proportion to the degree of coating matrix crystallization and phase separation. Transmission electron microscopy similarly showed damaged morphology of the inactivated virus vaccine associated with crystallization. In vivo assessment of immune response and protective efficacy in mice further showed reduced vaccine immunogenicity after influenza vaccination using microneedles with crystallized or phase-separated coatings. This work shows that crystallization and phase separation of the dried coating matrix are important factors affecting long-term stability of influenza vaccine-coated microneedles. PMID:22361098

  9. Viral vectors for avian influenza vaccines

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Prior to 2003, vaccines against avian influenza (AI) had limited, individual country or regional use in poultry. In late 2003, H5N1 high pathogenicity (HP) AI spread from China to multiple Southeast Asian countries, and to Europe during 2005 and Africa during 2006, challenging governments and all p...

  10. Preventing drug resistance in severe influenza

    NASA Astrophysics Data System (ADS)

    Dobrovolny, Hana; Deecke, Lucas

    2015-03-01

    Severe, long-lasting influenza infections are often caused by new strains of influenza. The long duration of these infections leads to an increased opportunity for the emergence of drug resistant mutants. This is particularly problematic for new strains of influenza since there is often no vaccine, so drug treatment is the first line of defense. One strategy for trying to minimize drug resistance is to apply periodic treatment. During treatment the wild-type virus decreases, but resistant virus might increase; when there is no treatment, wild-type virus will hopefully out-compete the resistant virus, driving down the number of resistant virus. We combine a mathematical model of severe influenza with a model of drug resistance to study emergence of drug resistance during a long-lasting infection. We apply periodic treatment with two types of antivirals: neuraminidase inhibitors, which block release of virions; and adamantanes, which block replication of virions. We compare the efficacy of the two drugs in reducing emergence of drug resistant mutants and examine the effect of treatment frequency on the emergence of drug resistant mutants.

  11. Rapid molecular diagnostic tools for avian influenza

    Technology Transfer Automated Retrieval System (TEKTRAN)

    An accurate and early diagnosis of a foreign animal disease is crucial for rapid control and eradication of an outbreak in a country previously free of the disease. Historically many animal diseases have been controlled based solely on clinical signs of disease. However with avian influenza virus ...

  12. Colleges and Universities Pandemic Influenza Planning Checklist

    ERIC Educational Resources Information Center

    Centers for Disease Control and Prevention, 2006

    2006-01-01

    In the event of an influenza pandemic, colleges and universities will play an integral role in protecting the health and safety of students, employees and their families. The Department of Health and Human Services (HHS) and the Centers for Disease Control and Prevention (CDC) have developed this checklist as a framework to assist colleges and…

  13. The changing face of swine influenza virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    "Flu" in pigs has been known for 90 years and on the surface it may appear as though little has changed. We still suspect flu when a high percentage of pigs have a sudden onset of barking cough, especially during temperature fluctuations in the fall or spring. However, the influenza viruses responsi...

  14. Avian influenza vaccines and vaccination for poultry

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Vaccines against avian influenza (AI) have had more limited use in poultry than vaccines against other poultry diseases such as Newcastle disease (ND) and infectious bronchitis, and have been used more commonly in the developing world. Over the past 40 years, AI vaccines have been primarily based o...

  15. Avian influenza vaccines and therapies for poultry

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Vaccines have been used in avian influenza (AI) control programs to prevent, manage or eradicate AI from poultry and other birds. The best protection is produced from the humoral response against the hemagglutinin (HA) protein. A variety of vaccines have been developed and tested under experimenta...

  16. Zanamivir in the treatment of influenza.

    PubMed

    Fleming, Douglas M

    2003-05-01

    Influenza is a common illness, affecting many people every winter, with a considerable impact on mortality, hospital admissions, healthcare utilisation and sickness absence from work and school. Influenza management is currently focused on annual vaccinations for those in certain risk groups. Risk is determined by age and chronic illness, particularly diabetes, chronic respiratory and cardiac disease, and persons immunocompromised from disease or concomitant therapy. Amantadine (and in some countries, rimantadine is available but has not been widely used, because it is only effective against influenza A infections. The use of amantadines for treatment has been associated with the rapid emergence of resistant viruses capable of transmission, compromising its potential as a prophylactic, as well as a treatment. Side effects are well recognised and are a particular problem in the most vulnerable elderly populations, where dose restriction is necessary and prior knowledge of creatinine clearance desirable. The potential market for a new influenza treatment is large and the potential role of neuraminidase inhibitors in addressing this market has been covered in several review articles [1-4]. This review reports on the introduction of zanamivir (Relenza) to the market with particular reference to experience in the UK. PMID:12740002

  17. Haemophilus influenzae Disease (Including Hib) Complications

    MedlinePlus

    ... Z Index MENU CDC A-Z SEARCH A B C D E F G H I J K L M N O P Q R S T U V W X Y Z # Start of Search Controls Search Form Controls Search The CDC Cancel Submit Search The CDC Haemophilus influenzae Disease (Including Hib) Note: Javascript is disabled or ...

  18. Influenza neuraminidase as a vaccine antigen

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The neuraminidase protein of influenza viruses is a surface glycoprotein that has enzymatic activity to remove sialic acid, the viral receptor, from both viral and host proteins. The removal of sialic acid from viral proteins plays a key role in the release of the virus from the cell by preventing ...

  19. Computational Approaches to Influenza Surveillance: Beyond Timeliness

    PubMed Central

    Nsoesie, Elaine O.; Brownstein, John S.

    2015-01-01

    Several digital data sources and systems have been advanced for use in augmenting traditional influenza surveillance systems. Although timeliness is one of the main advantage of these tools, there are several other recognizable uses and potential impact of these systems on the public and global public health. PMID:25766284

  20. Effect of Travel on Influenza Epidemiology

    PubMed Central

    Rimmelzwaan, Guus F.; van den Hoek, Anneke; Sonder, Gerard J.B.

    2013-01-01

    To assess the attack and incidence rates for influenza virus infections, during October 2006–October 2007 we prospectively studied 1,190 adult short-term travelers from the Netherlands to tropical and subtropical countries. Participants donated blood samples before and after travel and kept a travel diary. The samples were serologically tested for the epidemic strains during the study period. The attack rate for all infections was 7% (86 travelers) and for influenza-like illness (ILI), 0.8%. The incidence rate for all infections was 8.9 per 100 person-months and for ILI, 0.9%. Risk factors for infection were birth in a non-Western country, age 55–64 years, and ILI. In 15 travelers with fever or ILI, influenza virus infection was serologically confirmed; 7 of these travelers were considered contagious or incubating the infection while traveling home. Given the large number of travelers to (sub)tropical countries, travel-related infection most likely contributes to importation and further influenza spread worldwide. PMID:23735636

  1. Clinical and laboratory diagnosis of influenza.

    PubMed

    Rodrigo, Carlos; Méndez, Maria

    2012-01-01

    The clinical diagnosis of influenza can be very difficult or rather easy depending on the circumstances. It's easy when the epidemiological context is appropriate; the patient is a school kid or a teenager, and the symptoms are typical. On the other hand, it is hard when it fails to match any of the above premises, the more imformation that is missing, the more difficult it becomes. The symptomatology is correlated with age; therefore, typical clinical manifestations are only referred from 3-4 y old: rhinitis, fever with or without chills, cough, headache, joint and muscle pain and malaise. The patient often says he/she "feels sick" but his/her general condition is not at all serious. A rapid influenza diagnosis has been shown to reduce unnecessary test and antibiotics in pediatric patients and allows rational use of antivirals, early discharge from emergency departments and hospital wards, appropriate infection control measures and cohorting of infected patients. Tests that yield results in a timely manner that can influence clinical management are recommended to guide patient care. Results of testing should take into account the a priori likelihood of influenza infection based on the patient's signs and symptoms, the sensitivity and specificity of the test used, and information on circulation of influenza in the community. Failing to use the option of microbiological diagnosis when appropriate is a missed opportunity that can generate anxiety without justification, avoid unnecessarily antibiotics, omit antiviral therapy when convenient, and a teaching possibility. PMID:22251993

  2. Influenza Type A Viruses and Subtypes

    MedlinePlus

    ... virus infection of humans, such as with Asian-origin highly pathogenic avian influenza A (H5N1) viruses currently circulating among poultry in Asia and the Middle East have been reported in 16 countries, often resulting in severe pneumonia with approximately 60% ...

  3. A Defective Interfering Influenza RNA Inhibits Infectious Influenza Virus Replication in Human Respiratory Tract Cells: A Potential New Human Antiviral.

    PubMed

    Smith, Claire M; Scott, Paul D; O'Callaghan, Christopher; Easton, Andrew J; Dimmock, Nigel J

    2016-01-01

    Defective interfering (DI) viruses arise during the replication of influenza A virus and contain a non-infective version of the genome that is able to interfere with the production of infectious virus. In this study we hypothesise that a cloned DI influenza A virus RNA may prevent infection of human respiratory epithelial cells with infection by influenza A. The DI RNA (244/PR8) was derived by a natural deletion process from segment 1 of influenza A/PR/8/34 (H1N1); it comprises 395 nucleotides and is packaged in the DI virion in place of a full-length genome segment 1. Given intranasally, 244/PR8 DI virus protects mice and ferrets from clinical influenza caused by a number of different influenza A subtypes and interferes with production of infectious influenza A virus in cells in culture. However, evidence that DI influenza viruses are active in cells of the human respiratory tract is lacking. Here we show that 244/PR8 DI RNA is replicated by an influenza A challenge virus in human lung diploid fibroblasts, bronchial epithelial cells, and primary nasal basal cells, and that the yield of challenge virus is significantly reduced in a dose-dependent manner indicating that DI influenza virus has potential as a human antiviral. PMID:27556481

  4. A Defective Interfering Influenza RNA Inhibits Infectious Influenza Virus Replication in Human Respiratory Tract Cells: A Potential New Human Antiviral

    PubMed Central

    Smith, Claire M.; Scott, Paul D.; O’Callaghan, Christopher; Easton, Andrew J.; Dimmock, Nigel J.

    2016-01-01

    Defective interfering (DI) viruses arise during the replication of influenza A virus and contain a non-infective version of the genome that is able to interfere with the production of infectious virus. In this study we hypothesise that a cloned DI influenza A virus RNA may prevent infection of human respiratory epithelial cells with infection by influenza A. The DI RNA (244/PR8) was derived by a natural deletion process from segment 1 of influenza A/PR/8/34 (H1N1); it comprises 395 nucleotides and is packaged in the DI virion in place of a full-length genome segment 1. Given intranasally, 244/PR8 DI virus protects mice and ferrets from clinical influenza caused by a number of different influenza A subtypes and interferes with production of infectious influenza A virus in cells in culture. However, evidence that DI influenza viruses are active in cells of the human respiratory tract is lacking. Here we show that 244/PR8 DI RNA is replicated by an influenza A challenge virus in human lung diploid fibroblasts, bronchial epithelial cells, and primary nasal basal cells, and that the yield of challenge virus is significantly reduced in a dose-dependent manner indicating that DI influenza virus has potential as a human antiviral. PMID:27556481

  5. Influenza Surveillance and Incidence in a Rural Area in China during the 2009/2010 Influenza Pandemic

    PubMed Central

    Zhang, Ying; Li, Lin; Dong, Xiaochun; Kong, Mei; Gao, Lu; Dong, Xiaojing; Xu, Wenti

    2014-01-01

    Background Most influenza surveillance is based on data from urban sentinel hospitals; little is known about influenza activity in rural communities. We conducted influenza surveillance in a rural region of China with the aim of detecting influenza activity in the 2009/2010 influenza season. Methods The study was conducted from October 2009 to March 2010. Real-time polymerase chain reaction was used to confirm influenza cases. Over-the-counter (OTC) drug sales were daily collected in drugstores and hospitals/clinics. Space-time scan statistics were used to identify clusters of ILI in community. The incidence rate of ILI/influenza was estimated on the basis of the number of ILI/influenza cases detected by the hospitals/clinics. Results A total of 434 ILI cases (3.88% of all consultations) were reported; 64.71% of these cases were influenza A (H1N1) pdm09. The estimated incidence rate of ILI and influenza were 5.19/100 and 0.40/100, respectively. The numbers of ILI cases and OTC drug purchases in the previous 7 days were strongly correlated (Spearman rank correlation coefficient [r] = 0.620, P = 0.001). Four ILI outbreaks were detected by space-time permutation analysis. Conclusions This rural community surveillance detected influenza A (H1N1) pdm09 activity and outbreaks in the 2009/2010 influenza season and enabled estimation of the incidence rate of influenza. It also provides a scientific data for public health measures. PMID:25542003

  6. Influenza vaccine effectiveness in preventing inpatient and outpatient cases in a season dominated by vaccine-matched influenza B virus

    PubMed Central

    Martínez-Baz, Iván; Navascués, Ana; Pozo, Francisco; Chamorro, Judith; Albeniz, Esther; Casado, Itziar; Reina, Gabriel; Cenoz, Manuel García; Ezpeleta, Carmen; Castilla, Jesús

    2015-01-01

    Studies that have evaluated the influenza vaccine effectiveness (VE) to prevent laboratory-confirmed influenza B cases are uncommon, and few have analyzed the effect in preventing hospitalized cases. We have evaluated the influenza VE in preventing outpatient and hospitalized cases with laboratory-confirmed influenza in the 2012–2013 season, which was dominated by a vaccine-matched influenza B virus. In the population covered by the Navarra Health Service, all hospitalized patients with influenza-like illness (ILI) and all ILI patients attended by a sentinel network of general practitioners were swabbed for influenza testing, and all were included in a test-negative case-control analysis. VE was calculated as (1-odds ratio)×100. Among 744 patients tested, 382 (51%) were positive for influenza virus: 70% for influenza B, 24% for A(H1N1)pdm09, and 5% for A(H3N2). The overall estimate of VE in preventing laboratory-confirmed influenza was 63% (95% confidence interval (CI): 34 to 79), 55% (1 to 80) in outpatients and 74% (33 to 90) in hospitalized patients. The VE was 70% (41 to 85) against influenza B and 43% (−45 to 78) against influenza A. The VE against virus B was 87% (52 to 96) in hospitalized patients and 56% in outpatients (−5 to 81). Adjusted comparison of vaccination status between inpatient and outpatient cases with influenza B did not show statistically significant differences (odds ratio: 1.13; p = 0.878). These results suggest a high protective effect of the vaccine in the 2012–2013 season, with no differences found for the effect between outpatient and hospitalized cases. PMID:25996366

  7. Mutations in GABAA receptor subunits associated with genetic epilepsies.

    PubMed

    Macdonald, Robert L; Kang, Jing-Qiong; Gallagher, Martin J

    2010-06-01

    Mutations in inhibitory GABAA receptor subunit genes (GABRA1, GABRB3, GABRG2 and GABRD) have been associated with genetic epilepsy syndromes including childhood absence epilepsy (CAE), juvenile myoclonic epilepsy (JME), pure febrile seizures (FS), generalized epilepsy with febrile seizures plus (GEFS+), and Dravet syndrome (DS)/severe myoclonic epilepsy in infancy (SMEI). These mutations are found in both translated and untranslated gene regions and have been shown to affect the GABAA receptors by altering receptor function and/or by impairing receptor biogenesis by multiple mechanisms including reducing subunit mRNA transcription or stability, impairing subunit folding, stability, or oligomerization and by inhibiting receptor trafficking. PMID:20308251

  8. Simple sequence repeats in Haemophilus influenzae.

    PubMed

    Power, Peter M; Sweetman, W A; Gallacher, N J; Woodhall, M R; Kumar, G A; Moxon, E R; Hood, D W

    2009-03-01

    Simple sequence repeat (SSRs) of DNA are subject to high rates of mutation and are important mediators of adaptation in Haemophilus influenzae. Previous studies of the Rd KW20 genome identified the primacy of tetranucleotide SSRs in mediating phase variation (the rapid reversible switching of gene expression) of surface exposed structures such as lipopolysaccharide. The recent sequencing of the genomes of multiple strains of H. influenzae allowed the comparison of the SSRs (repeat units of one to nine nucleotides in length) in detail across four complete H. influenzae genomes and then comparison with a further 12 genomes when they became available. The SSR loci were broadly classified into three groups: (1) those that did not vary; (2) those for which some variation between strains was observed but this could not be linked to variation of gene expression; and (3) those that both varied and were located in regions consistent with mediating phase variable gene expression. Comparative analysis of 988 SSR associated loci confirmed that tetranucleotide repeats were the major mediators of phase variation and extended the repertoire of known tetranucleotide SSR loci by identifying ten previously uncharacterised tetranucleotide SSR loci with the potential to mediate phase variation which were unequally distributed across the H. influenzae pan-genome. Further, analysis of non-tetranucleotide SSR in the 16 strains revealed a number of mononucleotide, dinucleotide, pentanucleotide, heptanucleotide, and octanucleotide SSRs which were consistent with these tracts mediating phase variation. This study substantiates previous findings as to the important role that tetranucleotide SSRs play in H. influenzae biology. Two Brazilian isolates showed the most variation in their complement of SSRs suggesting the possibility of geographic and phenotypic influences on SSR distribution. PMID:19095084

  9. Evaluation of the limit of detection of the BD Veritor™ system flu A+B test and two rapid influenza detection tests for influenza virus.

    PubMed

    Peters, Timothy R; Blakeney, Elizabeth; Vannoy, Lauren; Poehling, Katherine A

    2013-02-01

    We evaluated the limits of detection of 3 rapid influenza diagnostic tests-BD Veritor™ System for Flu A+B, Binax NOW® Influenza A+B, and QuickVue® Influenza-for influenza strains circulating in 2010-2012. Limits of detection varied by influenza strain, with Veritor™ Flu A+B test showing the lowest limit of detection for all strains. PMID:23219228

  10. Conserved Features of the PB2 627 Domain Impact Influenza Virus Polymerase Function and Replication

    PubMed Central

    Kirui, James; Bucci, Michael D.; Poole, Daniel S.

    2014-01-01

    ABSTRACT Successful replication of influenza virus requires the coordinated expression of viral genes and replication of the genome by the viral polymerase, composed of the subunits PA, PB1, and PB2. Polymerase activity is regulated by both viral and host factors, yet the mechanisms of regulation and how they contribute to viral pathogenicity and tropism are poorly understood. To characterize these processes, we created a series of mutants in the 627 domain of the PB2 subunit. This domain contains a conserved “P[F/P]AAAPP” sequence motif and the well-described amino acid 627, whose identity regulates host range. A lysine present at position 627 in most mammalian viral isolates creates a basic face on the domain surface and confers high-level activity in humans compared to the glutamic acid found at this position in avian isolates. Mutation of the basic face or the P[F/P]AAAPP motif impaired polymerase activity, assembly of replication complexes, and viral replication. Most of these residues are required for general polymerase activity, whereas PB2 K586 and R589 were preferentially required for function in human versus avian cells. Thus, these data identify residues in the 627 domain and other viral proteins that regulate polymerase activity, highlighting the importance of the surface charge and structure of this domain for virus replication and host adaptation. IMPORTANCE Influenza virus faces barriers to transmission across species as it emerges from its natural reservoir in birds to infect mammals. The viral polymerase is an important regulator of this process and undergoes discrete changes to adapt to replication in mammals. Many of these changes occur in the polymerase subunit PB2. Here we describe the systematic analysis of a key region in PB2 that controls species-specific polymerase activity. We report the importance of conserved residues that contribute to the overall charge of the protein as well as those that likely affect protein structure. These

  11. Physical and immunogenic stability of spray freeze-dried influenza vaccine powder for pulmonary delivery: comparison of inulin, dextran, or a mixture of dextran and trehalose as protectants.

    PubMed

    Murugappan, Senthil; Patil, Harshad P; Kanojia, Gaurav; ter Veer, Wouter; Meijerhof, Tjarko; Frijlink, Henderik W; Huckriede, Anke; Hinrichs, Wouter L J

    2013-11-01

    One of the advantages of dry influenza vaccines over conventional liquid influenza vaccines is that they can be used for alternative routes of administration. Previous studies showed that spray freeze-drying is an excellent technique to prepare vaccine containing powders for pulmonary delivery (J.P. Amorij, V. Saluja, A.H. Petersen, W.L.J. Hinrichs, A. Huckriede, H.W. Frijlink, Pulmonary delivery of an inulin-stabilized influenza subunit vaccine prepared by spray-freeze drying induces systemic, mucosal humoral as well as cell-mediated immune responses in BALB/c mice, Vaccine 25 (2007) 8707-8717; S.A. Audouy, G. van der Schaaf, W.L.J. Hinrichs, H.W. Frijlink, J. Wilschut, A. Huckriede. Development of a dried influenza whole inactivated virus vaccine for pulmonary immunization, Vaccine (2011)). The aim of this study was to investigate the physical and immunogenic stability of spray freeze-dried whole inactivated virus influenza vaccine prepared by using inulin, dextran, and a mixture of dextran and trehalose as protectants. Physical and biochemical characteristics of the vaccine powder were maintained at temperatures up to 30 °C for 3 months. In addition, in vivo data indicate that also, the immunogenic properties of the vaccine were maintained under these storage conditions. On the other hand, in vivo results also revealed that subtle changes in powder characteristics were induced during storage at 30 °C. However, laser diffraction measurements showed that problems associated with these subtle changes can be overcome by using dry powder inhalers with an efficient powder dispersing capacity. PMID:23933147

  12. Development of Framework for Assessing Influenza Virus Pandemic Risk

    PubMed Central

    Burke, Stephen A.; Cox, Nancy J.

    2015-01-01

    Although predicting which influenza virus subtype will cause the next pandemic is not yet possible, public health authorities must continually assess the pandemic risk associated with animal influenza viruses, particularly those that have caused infections in humans, and determine what resources should be dedicated to mitigating that risk. To accomplish this goal, a risk assessment framework was created in collaboration with an international group of influenza experts. Compared with the previously used approach, this framework, named the Influenza Risk Assessment Tool, provides a systematic and transparent approach for assessing and comparing threats posed primarily by avian and swine influenza viruses. This tool will be useful to the international influenza community and will remain flexible and responsive to changing information. PMID:26196098

  13. Influenza and the use of oseltamivir in children.

    PubMed

    Çiftçi, Ergin; Karbuz, Adem; Kendirli, Tanıl

    2016-06-01

    Influenza is an infectious disease which causes significant morbidity and mortality. In the USA, approximately 200 000 hospital admissions and 36 000 deaths occur annualy due to severe influenza infections. Although influenza often causes a simple respiratory infection, it sometimes causes disorders affecting several organs including the lung, heart, brain, liver and muscles or serious life-threatening primary viral or secondary bacterial pneumonia. Currently, oseltamivir is the most important and effective drug for severe influenza infections. Severe influenza infections can be controlled and related deaths may be prevented with initiation of this drug especially within first 2 days. Oseltamivir is usually well tolerated and its most commonly reported side effect is related with the gastrointestinal system. In conclusion, the course of influenza changes in a positive direction and the rates of complications and mortality significantly reduce in patients in whom oseltamivir treatment is initiated as soon as possible. PMID:27489462

  14. Origin of the European avian-like swine influenza viruses.

    PubMed

    Krumbholz, Andi; Lange, Jeannette; Sauerbrei, Andreas; Groth, Marco; Platzer, Matthias; Kanrai, Pumaree; Pleschka, Stephan; Scholtissek, Christoph; Büttner, Mathias; Dürrwald, Ralf; Zell, Roland

    2014-11-01

    The avian-like swine influenza viruses emerged in 1979 in Belgium and Germany. Thereafter, they spread through many European swine-producing countries, replaced the circulating classical swine H1N1 influenza viruses, and became endemic. Serological and subsequent molecular data indicated an avian source, but details remained obscure due to a lack of relevant avian influenza virus sequence data. Here, the origin of the European avian-like swine influenza viruses was analysed using a collection of 16 European swine H1N1 influenza viruses sampled in 1979-1981 in Germany, the Netherlands, Belgium, Italy and France, as well as several contemporaneous avian influenza viruses of various serotypes. The phylogenetic trees suggested a triple reassortant with a unique genotype constellation. Time-resolved maximum clade credibility trees indicated times to the most recent common ancestors of 34-46 years (before 2008) depending on the RNA segment and the method of tree inference. PMID:25073465

  15. Prevention, diagnosis, and treatment of influenza: current and future options.

    PubMed

    Poehling, K A; Edwards, K M

    2001-02-01

    Because influenza significantly affects the health of children, this review describes the current and future options for preventing, diagnosing, and treating influenza infections. Currently, the inactivated influenza vaccine is recommended for prevention of influenza; however, the live, attenuated, intranasal influenza vaccine is a potential future option. For diagnosis, viral culture is the gold standard, although four rapid diagnostic tests are available for more immediate results. The impetus for rapid results is the availability of effective antiviral agents indicated for early influenza infection. The four currently approved antiviral agents are amantadine, rimantadine, zanamivir [Relenza, Glaxo Wellcome, Inc., Research Triangle Park, NC] and oseltamivir [Tamiflu, Roche Pharmaceuticals, Nutley, NJ]. The indications, benefits, side effects and ages for which each drug is approved are reviewed. PMID:11176246

  16. Advances in the Diagnosis and Management of Influenza.

    PubMed

    Jefferson, Tom

    2002-06-01

    Vaccines are the mainstay of influenza prevention. In the treatment of a likely or certain case of influenza, ion channel inhibitors (amantadine and rimantadine) and neuraminidase inhibitors (oseltamivir and zanamivir) can be effective in reducing the duration of illness in adults. In the absence of a likely or certain influenza diagnosis, ion channel inhibitors or neuramindase inhibitors have lower effectiveness, and symptom relief becomes the rationale for treatment of influenza-like illness. Because both influenza and influenza-like illness are self-limiting, safety of interventions is paramount, especially in children. Echinacea extracts, steam, chicken soup, ipatropium bromide, and oxymetazoline in adults are the interventions that appear to have the best empirical evidence. PMID:12015912

  17. Confined animal feeding operations as amplifiers of influenza.

    PubMed

    Saenz, Roberto A; Hethcote, Herbert W; Gray, Gregory C

    2006-01-01

    Influenza pandemics occur when a novel influenza strain, often of animal origin, becomes transmissible between humans. Domestic animal species such as poultry or swine in confined animal feeding operations (CAFOs) could serve as local amplifiers for such a new strain of influenza. A mathematical model is used to examine the transmission dynamics of a new influenza virus among three sequentially linked populations: the CAFO species, the CAFO workers (the bridging population), and the rest of the local human population. Using parameters based on swine data, simulations showed that when CAFO workers comprised 15-45% of the community, human influenza cases increased by 42-86%. Successful vaccination of at least 50% of CAFO workers cancelled the amplification. A human influenza epidemic due to a new virus could be locally amplified by the presence of confined animal feeding operations in the community. Thus vaccination of CAFO workers would be an effective use of a pandemic vaccine. PMID:17187567

  18. Influenza virus vaccine for neglected hosts: horses and dogs.

    PubMed

    Na, Woonsung; Yeom, Minjoo; Yuk, Huijoon; Moon, Hyoungjoon; Kang, Bokyu; Song, Daesub

    2016-07-01

    This study provides information regarding vaccine research and the epidemiology of influenza virus in neglected hosts (horses and dogs). Equine influenza virus (EIV) causes a highly contagious disease in horses and other equids, and outbreaks have occurred worldwide. EIV has resulted in costly damage to the horse industry and has the ability of cross the host species barrier from horses to dogs. Canine influenza is a virus of equine or avian origin and infects companion animals that live in close contact with humans; this results in possible exposure to the seasonal epizootic influenza virus. There have been case reports of genetic reassortment between human and canine influenza viruses, which results in high virulence and the ability of transmission to ferrets. This emphasizes the need for vaccine research on neglected hosts to update knowledge on current strains and to advance technology for controlling influenza outbreaks for public health. PMID:27489801

  19. Edible bird's nest extract inhibits influenza virus infection.

    PubMed

    Guo, Chao-Tan; Takahashi, Tadanobu; Bukawa, Wakoto; Takahashi, Noriko; Yagi, Hirokazu; Kato, Koichi; Hidari, Kazuya I-P Jwa; Miyamoto, Daisei; Suzuki, Takashi; Suzuki, Yasuo

    2006-07-01

    Edible bird's nest (EBN) is the nest of the swift that is made from its saliva. Although EBN has been widely used for enhancing immunocompetence, its antiviral efficacy has not been studied in detail. We found that EBN extract could strongly inhibit infection with influenza viruses in a host range-independent manner when it was hydrolyzed with Pancreatin F. Western blotting assay showed that the EBN extract bound to influenza virus. Furthermore, EBN extract could neutralize the infection of MDCK cells with influenza viruses and inhibit hemagglutination of influenza viruses to erythrocytes, but it could not inhibit the activity of influenza virus sialidase. Fluorometric HPLC indicated that the major molecular species of sialic acid in EBN is N-acetylneuraminic acid. The results suggest that EBN is a safe and valid natural source for the prevention of influenza viruses. PMID:16581142

  20. The preventive and therapeutic potential of natural polyphenols on influenza.

    PubMed

    Bahramsoltani, Roodabeh; Sodagari, Hamid Reza; Farzaei, Mohammad Hosein; Abdolghaffari, Amir Hossein; Gooshe, Maziar; Rezaei, Nima

    2016-01-01

    Influenza virus belongs to orthomyxoviridae family. This virus is a major public health problems, with high rates of morbidity and mortality. Despite a wide range of pharmacotherapeutic choices inhibiting specific sequences of pathological process of influenza, developing more effective therapeutic options is an immediate challenge. In this paper, a comprehensively review of natural polyphenolic products used worldwide for the management of influenza infection is presented. Cellular and molecular mechanisms of the natural polyphenols on influenza infection including suppressing virus replication cycle, viral hemagglutination, viral adhesion and penetration into the host cells, also intracellular transductional signaling pathways have been discussed in detail. Based on cellular, animal, and human evidence obtained from several studies, the current paper demonstrates that natural polyphenolic compounds possess potential effects on both prevention and treatment of influenza, which can be used as adjuvant therapy with conventional chemical drugs for the management of influenza and its complications. PMID:26567957