Dissertations / Theses on the topic 'Influenza B virus'
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1
Pavan, Carmen M. "Influenza B virus : segment 7 gene expression." Thesis, McGill University, 1989. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=55673.
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Rowley, Kathryn Victoria. "Genetic manipulation of influenza B virus segment 6." Thesis, University of Reading, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.314321.
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MAENO, KOICHIRO. "Replication of Influenza B Virus: Biological Functions of Viral Neuraminidase." Nagoya University School of Medicine, 1994. http://hdl.handle.net/2237/15935.
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Tsang, Chi-ho, and 曾志豪. "A multi-probe quantitative PCR assay for genotyping of influenza B virus." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2012. http://hub.hku.hk/bib/B49828599.
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Influenza B virus contributes to a significant portion of influenza disease burden in men. It is structurally similar and replicates in the same manner as the influenza A virus, leading to a comparable clinical presentation between the two viral species. Since 1977, influenza B has caused seasonal epidemics around the world together with A/H1N1 and A/H3N2 subtypes, and has a strong affinity to affect children of school age and young adults.
In the 1980s, two antigenically distinct lineages of influenza B virus emerged, one being the B/Yamagata lineage and the other known as B/Victoria lineage. The most significant antigenic difference between the two is located in the HA1 domain of the viral hemagglutinin. Host immunity is not shared between the two viral lineages. Therefore, the global prevalence of the two influenza B lineages is closely monitored by the World Health Organization in order to decide which viral lineage to include in the annual trivalent influenza vaccines.
Surprisingly, the current methods used in influenza B viral surveillance and lineage discrimination have not seen much technical advancement in nearly 25 years since the emergence of two viral lineages. The current study presents a novel, asymmetric real-time PCR assay which is able to determine the viral lineage in addition to detecting the presence of influenza B virus in clinical specimens.
Asymmetric PCR is performed by deliberately limiting the amount of primers in one side of a PCR reaction. This significantly affects the replication efficiency and sensitivity of the PCR reaction, but at the same time facilitates target sequence detection by hybridization probes, due to an increased number of single stranded products in the reaction. Nevertheless, the use of asymmetric PCR has been avoided in the past. The recent introduction of linear-after-the-exponential (LATE) PCR refines the method by adjusting melting temperature of PCR primers so that TmLimiting – TmExcess ≥ 0°C. The modification is shown to raise the efficiency of asymmetric PCR to those of symmetric PCR, as well as allowing more relaxed criteria for PCR primer and probe design.
In the current asymmetric assay, pan-influenza B primers and probes targeting Victoria and Yamagata linage specific regions of the influenza B HA were evaluated against a similar symmetric influenza B assay published by the World Health Organization. HA plasmid standards and 155 clinical specimens were tested by both assays, in which the two had intra-assay CV% of less than 5%. Albeit the efficiency and sensitivity of WHO published assay was slightly higher, LATE-PCR based assay performed influenza B detection and genotyping simultaneously with the use of hydrolysis probes. The overall sensitivity/ specificity of the genotyping assay are 96.81%/100% while the WHO recommended assay is at 98.94%/100% for influenza B detection. The LATE-PCR based genotyping assay also successfully genotyped 89 out of 94 clinical specimens.
In conclusion, the influenza B genotyping assay evaluated in this study performed favorably and could serve as an alternative to cumbersome viral culture methods to aid in high-throughput global influenza surveillance.published_or_final_version
Microbiology
Master
Master of Medical Sciences
5
Huang, Kuan-Ying. "B cell and antibody responses to influenza A virus in human." Thesis, University of Oxford, 2011. http://ora.ox.ac.uk/objects/uuid:3c24c905-15e2-4547-944e-e1a46a6aacd0.
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Neutralising antibodies and antigen-specific B cells are important for protection against influenza A virus. However, the antigenic evolution of influenza A viruses has made a continuing challenge to the design of vaccine and the public health. The ability to generate cross-reactive response against influenza remains unclear in human. It is important to explore the antibody and B cell repertoire at single cell level. The pandemic H1N1 and seasonal influenza vaccine induced robust antibody response in adults. However, pre- or co-vaccination with the seasonal vaccine led to a significantly reduced antibody response to pandemic H1N1 virus. Whether this interference has impact on subsequent infection rates remains undetermined. There observed substantial cross-reactive antibody response upon vaccination, as measured by HI, MN and B cell ELISpot assays. The antibody recognizing conserved proteins could be the main component of cross-reactivity against influenza A strains and subtypes. A significant expansion of influenza-specific MBC was observed after infection. Crossreactive response was also noted in the MBC response. Importantly, a robust early-phase ASC response was detected in the peripheral blood upon influenza vaccination or infection. The size of ASC response significantly correlated with serum HI, MN and anti-HA IgG titre three weeks after vaccination. The sequence analysis revealed that early-phase ASC accumulated high level of somatic mutations on Ig variable region and affinity maturation, as well as anti-influenza mAb, which suggested their origin from pre-existing MBC. Eight anti-influenza mAb were made from early-phase ASC, including one high-titre virus-neutralising HA1-specific, two other HA1-specific, one cross-reactive HA2-specific, and four cross-reactive NP-specific antibodies, indicating of the broad diversity of ASC repertoire. In conclusion, this study demonstrated the properties of antibody and B cell responses to influenza A virus at serological, cellular and sequence level. The virus-neutralising and cross-reactive mAb derived from ASC could have therapeutic potential and their analysis might direct the vaccine design in the near future.
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Schneider, Jana [Verfasser]. "Charakterisierung nuklearer Funktionen des Nichtstrukturproteins von Influenza-B-Virus / Jana Schneider." Berlin : Freie Universität Berlin, 2009. http://d-nb.info/1023665859/34.
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Boyden, Alexander Wiser. "Influenza A virus induces regulated T cell-driven B cell responses." Diss., University of Iowa, 2012. https://ir.uiowa.edu/etd/3432.
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Protection from influenza A virus (IAV) challenge requires switched, high affinity Abs derived from long-lived memory B cells and plasma cells. These subsets are generated in germinal centers (GCs), hallmark structures of T helper cell-driven B cell immunity. A full understanding of the acute and persistent GC B cell reaction following respiratory IAV infection is lacking, as is the characterization of IAV-induced T follicular helper (TFH) cells that support GCs. Additionally, it remains unclear as to whether IAV-induced GC B cells are subject to control by regulatory T cells (Tregs). To address this, GC B cell and TFH cell responses were analyzed in mice following pulmonary challenge with IAV. Studies demonstrated that marked GC reactions were induced in lung-draining lymph nodes (dLNs), lung, spleen and nasal-associated lymphoid tissue (NALT), although the magnitude, kinetics, and isotype switching patterns of the response was site-specific, and largely depended on the magnitude of IAV-induced TFH cell populations. TFH cell magnitude peaked prior to that of GC B cells in all tissues, and TFH cells purified from dLNs generated IL-21 and IFN-gamma upon activation, although CD4+CXCR5- T effector cells produced higher levels of all cytokines. IgA+ GC B cells were infrequent in most sites, but composed a significant subset of the switched GC population in NALT. Further, splenectomized mice withstood a lethal recall challenge, suggesting the spleen to be unnecessary for long-term protection. Additionally, GC B cell populations were analyzed at distal time points to assess the understudied, persistent GC B cell response after IAV infection. Our analysis demonstrated that persistent GC B cell populations in mouse lungs directly correlated with infectious dose, pathogenicity of the virus, as well as the presence of long-term CD4+ T cell help. Finally, experiments showed that Tregs contribute to the control of GCs induced in the spleen by IAV challenge. This was demonstrated by a marked increase in the number of total and switched GC B cell numbers when Tregs were either depleted or disrupted in vivo proximal to IAV exposure.
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INOUE, HIROMASA, and ARIFUMI KUNO. "Antigenic Analysis of Influenza B Virus Isolated from the Epidemic in 1973." Nagoya University School of Medicine, 1985. http://hdl.handle.net/2237/17471.
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Wang, Xiaohui, and 王晓辉. "The role of IL-17A in modulating B cell response during influenza virus infection." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2014. http://hdl.handle.net/10722/208035.
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Interleukin-17A (IL-17A)is an important pro-inflammatory cytokine that plays a critical role in host defenses against diverse pathogens. Studies have shown that IL-17Aplays protective role against sub-lethal H1 and H3 subtypes influenza infections, but it is unclear about the role of IL-17A in the highly pathogenic H5N1 and lethal H1N1 influenza virus infection. B cell is an important effector cell type in anti-influenza immunity. Although roles of B cell in influenza infection have been extensively investigated, it is unclear whether and how IL-17AregulatesB cell response during influenza infection.
I examined the role of IL-17A against influenza infection by challengingIL-17A knockout (KO) and wild-type (WT) mice with highly pathogenic H5N1 and lethal H1N1 influenza viruses. Following challenge, IL-17AKO mice exhibited significantly lower survival rate, profoundly reduced body weight, more severe tissue damage and higher viral burden in the lung tissues. These evidences suggest that IL-17Aplays a protective role in lethal influenza infection.
To study whether IL-17Amodulates B cell response against influenza, I found that both B-1a and B-2 cells were detected in the lung tissue and pulmonary draining lymph node, Mediastinal lymph node (MedLN),as early as 2days post-infection. Meanwhile, B-1a cells predominantly contributed to the early virus-specific IgM in the respiratory tract. However, virus-specific IgM markedly reduced in IL-17A KO mice when compared with WT controls. Adoptive transfer of B-1a cells or B-1a cell-derived antibodies conferred protection in IL-17A KO mice. These results demonstrate that IL-17A plays a critical role in modulating early antibody production of B-1a cells against lethal influenza infection.
To further elucidate how IL-17A regulates B-1a cell response, I observed that B-1a cells migrated into MedLN and lung tissues during infection and underwent plasmacytic differentiation with increased antibody production in airways. IL-17A deficiency impaired these processes of B-1a cells, while intra-nasally instillation of IL-17A restored B-1a cell response by promoting both B-1a cell migration and plasmacytic differentiation. By inducing blimp-1 expression in B-1a cells in an NF-κB dependent pathway, IL-17A directly promoted plasmacytic differentiation of B-1a cells both in vivo and in vitro. Furthermore, chromatin immuno-precipitation analysis confirmed that NF-κB directly bound to the promoter of blimp-1 gene and promoted blimp-1 expression in B-1a cells following IL-17A stimulation.
To determine the functional significance of IL-17A signaling in modulating B cell response against influenza infection, I first uncovered markedly reduced B cell response, predominantly B-1a cell response in IL-17A KO mice, showing reduced local migration and impaired plasmacytic differentiation in the early stage of infection. Next, intra-nasal administration of IL-17A into IL-17A KO mice significantly restored this B-1a cell response. Moreover, I detected expression of IL-17A receptor in B-1a cells. IL-17A treatment could promote antibody production from B-1a cells by inducing blimp-1 expression in an NF-κB dependent pathway.
Taken together, these findings identify a novel role of IL-17A in actingas an immune modulator of B cell response against influenza infection, which will contribute to a fuller understanding of B cell biology and anti-viral response in host defense.published_or_final_version
Pathology
Doctoral
Doctor of Philosophy
10
Audsley, Jennifer M., and jennifer audsley@med monash edu au. "Alternative Approaches In The Preparation And Growth Of Influenza B Vaccine Viruses." RMIT University. Applied Sciences, 2008. http://adt.lib.rmit.edu.au/adt/public/adt-VIT20080414.141937.
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Influenza B viruses are a significant cause of disease and influenza B antigens are present in all human vaccines. Achieving suitable yields of seed viruses is often difficult for vaccine manufacturers. With influenza A viruses increases in yields have been achieved by the preparation of reassortants between a high-yielding donor strain and an epidemic strain. However, reassortment of influenza B viruses for the preparation of seeds has not been usually undertaken due to the lack suitable donor strains. Such an approach, which formed the basis of this thesis, could improve vaccine yields, lower costs and introduce a further element of predictability to vaccine manufacture. Potential donor strains were prepared from B/Lee/40 (B/Lee) by two approaches involving the selection of stable cold- and high- temperature mutants. Initial passaging was undertaken in specific-pathogen-free (SPF) chicken embryo kidney (CEK) cultures and later passage in SPF embryonated chicken eggs. Both approaches were successful, although a smaller number of viable progeny could be isolated from plaques obtained at 38aC. Potential donor strains, isolated by selection at either 25 or 38aC and plaque-purified in SPF CEK cultures, were tested for haemagglutinin and infectious titre, in comparison with the original parental strain by three methods, and for differences in antigenicity by cross-haemagglutination-inhibition tests. Potential donor strains selected at temperatures of 25aC (C25) and 38aC (H38) produced haemagglutination titres of 320 units/50ÝL and infectivities of 8.57 and 8.39 50% egg infectious doses, respectively, when grown in eggs at the permissive temperature (34aC). Reassorting experiments using the B/Lee-derived potential donor strains C25 and H38 and the epidemic strain, B/Johannesburg/5/99 (B/Johannesburg), showed that the preparation of reassortant progeny with both epidemic strain HA and NA was difficult. Only 1/24 of the resulting reassortants possessed both the HA and NA of the epidemic strain. None of the reassortant progeny produced in reassorting experiments using C25 and H38 and the epidemic strain B/Panama/45/90 (B/Panama) possessed the desired 6:2 gene constellation (i.e. genes for the two surface antigens of the epidemic strain and the remainder from the donor strain). The infectious titre of selected progeny from the reassortment experiments were determined by three methods and compared with their respective epidemic parents. Yields of several influenza B epidemic strains and potential donor strains were measured after growth in Madin-Darby canine kidney (MDCK) cells prepared in serum-containing (SC) and animal- and human-derived protein-free (AHPF) media. Optimal multiplicities of infection were determined for B/Panama, B/Johannesburg and C25 in MDCK cultures grown in SC medium. A series of experiments were then undertaken to determine the maximum virus yields in MDCK cells grown in SC medium, followed by a further experiment using C25, B/Panama, B/Johannesburg, and selected reassortants after preparation in AHPF medium. Cell culture yields from 5/6 viruses grown in MDCK cells prepared in AHPF medium were higher than in cells prepared in SC medium and approached those obtained in eggs.
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Reiche, Sven, Yamen Dwai, Bianca M. Bussmann, Susanne Horn, Michael Sieg, and Christian Jassoy. "High inter-individual diversity of point mutations, insertions, and deletions in human influenza virus nucleoprotein-specific memory B cells." Universitätsbibliothek Leipzig, 2015. http://nbn-resolving.de/urn:nbn:de:bsz:15-qucosa-172324.
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The diversity of virus-specific antibodies and of B cells among different individuals is unknown. Using single-cell cloning of antibody genes, we generated recombinant human monoclonal antibodies from influenza nucleoprotein-specific memory B cells in four adult humans with and without preceding influenza vaccination. We examined the diversity of the antibody repertoires and found that NP-specific B cells used numerous immunoglobulin genes. The heavy chains (HCs) originated from 26 and the kappa light chains (LCs) from 19 different germ line genes. Matching HC and LC chains gave rise to 43 genetically distinct
antibodies that bound influenza NP. The median lengths of the CDR3 of the HC, kappa and lambda LC were 14, 9 and 11 amino acids, respectively. We identified changes at 13.6% of the amino acid positions in the V gene of the antibody heavy chain, at 8.4 % in the kappa and at 10.6 % in the lambda V gene. We identified somatic insertions or deletions in 8.1% of the variable genes. We also found several small groups of clonal relatives that were highly diversified. Our findings demonstrate broadly diverse memory B cell repertoires for the influenza nucleoprotein. We found extensive variation within individuals with a high number of point mutations, insertions, and deletions, and extensive clonal diversification. Thus, structurally conserved proteins can elicit broadly diverse and highly mutated B-cell responses.
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Sherry, Lee. "Investigating the antiviral activity of the interferon-inducible GTPase MxA against influenza viruses." Thesis, University of St Andrews, 2016. http://hdl.handle.net/10023/8072.
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The interferon (IFN) system forms an essential part of the innate immune response, up-regulating hundreds of IFN-stimulated genes (ISGs) in response to viral infection. A key protein in this response is the human myxovirus resistance protein MxA, an IFN-induced GTPase with broad-spectrum antiviral activity, capable of inhibiting many RNA and DNA viruses. One of the most studied antiviral effects of MxA is the inhibition of influenza A virus replication, yet the molecular mechanism of antiviral activity is still unknown. Influenza A viruses are inhibited by MxA at two distinct stages of viral replication; during viral entry and following primary transcription of viral mRNAs. The antiviral effects of MxA during viral entry are highly dependent on IFN, however activity exerted after primary transcription can occur in the absence of IFN. This study provides evidence that MxA exerts its antiviral activity at these two stages of viral replication through distinct mechanisms, and outlines a potential model of MxA antiviral activity following primary transcription. A potential third antiviral mechanism of MxA is proposed based on the findings that MxA is able to regulate cellular lipid metabolism, thereby potentially affecting virion composition. Mutational analysis of MxA highlights the significance of GTPase activity to the antiviral effects of MxA, while also demonstrating that natural single nucleotide polymorphisms in MxA have the potential to severely impair or prevent antiviral activity. Finally, this thesis shows for the first time that MxA exhibits antiviral activity against influenza B viruses. Overall this thesis provides new information illustrating how MxA provides potent antiviral activity against influenza viruses. Such information is vitally important as understanding the molecular basis of how proteins such as MxA function against many human pathogens is fundamentally important in our efforts to create better long-term treatment options for all viral diseases.
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Ng, Hoi-yee Iris, and 吳凱怡. "Serological diagnosis of influenza B virus infection in pigs : a comparison of the hemagglutination inhibition assay and the cell-based ELISA assay." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2013. http://hdl.handle.net/10722/193797.
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Background
Swine influenza virus (SIV) was first isolated in the United States in 1930 and was thereafter widely reported in many countries. Most SIVs that have been identified are influenza A viruses. There was no report of influenza B viruses isolated in swine. Seroepidemiological study in UK has shown a low seroprevalence of influenza B antibody in pigs. The primary serological test used to detect influenza antibody is the hemagglutination inhibition (HI)test. Enzyme-linked immunosorbent assay (ELISA) are also available commercially for detection of antibodies against influenza A viruses but not for the detection of influenza B antibodies.
Objectives
1) To examine the prevalence of influenza B antibodies in pig sera sampled at the abattoir in Hong Kong.
2) To develop the cell-based ELISA assay for the detection of antibodies against influenza A and B viruses.
3) To compare the cell-based ELISA assays with three commercial ELISA kits, namely the IDVet ID Screen influenza A antibody competition ELISA, the IDEXX Influenza A Ab test and the IDEXX AI MultiS-Screen Ab test using swine sera.
4) To test swine sera using the influenza B cell-based ELISA assay to complement data on swine seroprevalence obtained with HI tests.
Methods
The first part of this study involved HI screening of 4643 pig sera from 2009 to 2012. These sera were tested for the presence of antibodies against B/Brisbane/60/2008 and B/Wisconsin/1/2010whichrepresent the B/Victoria and B/Yamagata lineages respectively.
The second part of this study involved the development and performance evaluation of the cell-based ELISA assays. The cell-based ELISA assays were developed using influenza virus infected cells as the capture antigens and fluorescence-labelled anti-IgG antibody as the detection antibody. The viruses that were used to prepare the assays were A/California/04/2009, B/Brisbane/60/2008 and B/Wisconsin/1/2010. All three cell-based ELISA assays were tested with WHO reference sera and swine sera and the results were analyzed using paired t-test and receiver operating characteristic analysis. In addition, the results of the influenza A cell-based ELISA assay were compared with the commercial ELISA assay using Fisher’s exact two-tailed test, Pearson’s correlation analysis and Bland-Altman plot.
Results
A low prevalence (0.28%; 95%CI: 0.16%-0.47%) of influenza B antibody was observed inthe swine sera samples. The seroprevalence for B/Victoria was higher than that of B/Yamagatain 2010to2012. Co-existence of B/Victoria and B/Yamagata antibodies were found in the swine population during 2010 and 2011.
The influenza A cell-based ELISA was found to have low sensitivity (64.1%;95%CI: 52.4%-74.4%) and high specificity (94.7%; 95%CI:80.9%-99.1%) when compared with the commercial ELISA assays. In contrast, using HI as the reference test influenza B cell-based ELISA prepared using B/Wisconsin/1/2010 infected cells were shown to have high sensitivity (92.31%; 95%CI:64.0%-99.8%) but low specificity (63.16%;95%CI:38.4%-83.7%) in detection of influenza B antibodies in swine sera.
Conclusion
Sporadic transmission of influenza B virus may occur in swine but there is no evidence for efficient and sustained transmission of the virus between them. Cell-based ELISA assay prepared with B/Wisconsin/1/2010 may be considered as an alternative screening testprior to HI subtyping.published_or_final_version
Public Health
Master
Master of Public Health
14
Wurzer, Walter. "Die Rolle des Transkriptionsfaktors NF-kB [NF-kappa-B] in Influenza-A-Virus-infizierten Zellen." [S.l.] : [s.n.], 2003. http://deposit.ddb.de/cgi-bin/dokserv?idn=968366732.
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Yuan, Weiming. "Novel anti-interferon mechanism : influenza B virus both induces and blocks the activity of the ubiquitin-like ISG15 protein /." Full text (PDF) from UMI/Dissertation Abstracts International, 2000. http://wwwlib.umi.com/cr/utexas/fullcit?p9992947.
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Turnbull, Matthew Luke. "The role of the NS segment of Influenza A virus in setting host range and pathogenicity." Thesis, University of Edinburgh, 2017. http://hdl.handle.net/1842/25468.
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Influenza A virus (IAV) circulates in waterfowl, causing mostly asymptomatic infections. IAV can undergo host adaptation and evolve to cause significant disease and mortality in domestic poultry and mammals, applying an enormous socio-economic burden on society. Sporadically, IAV causes global pandemics in man due to its zoonotic nature, and this can result in millions of deaths worldwide during a single outbreak. Host adaptation of IAV is an incompletely understood phenomenon, but is known to involve both host and viral determinants. It is essential to improve the understanding of the factors governing host range and pathogenicity of avian IAV, especially given the absence of a universal influenza vaccine and a limited weaponry of effective antiviral compounds. This study set out to improve the understanding of host adaptation of avian IAV, focussing on segment 8 (NS segment) of the virus genome. The NS segment of non-chiropteran IAV circulates as two phylogenetically distinct clades – the ‘A-’ and ‘B-alleles’. The A-allele is found in avian and mammalian viruses, but the B-allele is considered to be almost exclusively avian. This might result from one or both of the major NS gene products (NS1 and NEP) being non-functional in mammalian host cells, or from an inability of segment 8 RNA to package into mammalian-adapted strains. To investigate this, the NS segments from a panel of avian A- and B-allele strains were introduced into human H1N1 and H3N2 viruses by reverse genetics. A- and B-allele reassortant viruses replicated equally well in a variety of mammalian cell types in vitro. Surprisingly, the consensus B-allele segment 8 out-competed an A-allele counterpart when reassortant H1N1 viruses were co-infected, with the parental WT segment 8 being most fit in this system. A- and B-allele NS1 proteins were equally efficient at blocking the mammalian IFN response both in the context of viral infection and in transfection-based reporter assays. Consensus A- and B-allele H1N1 viruses also caused disease in mice and replicated to high virus titre in the lung. Interestingly, the B-allele virus induced more weight-loss than the A-allele, although the parental WT virus was most pathogenic in vivo. To re-address the hypothesis that B-allele NS genes really are avian-restricted, the relative rates of independent Aves to Mammalia incursion events of A- and B-allele lineage IAV strains was estimated and compared using phylogenetic analyses of all publically available segment 8 sequences. 32 A-allele introduction events were estimated compared to 6 B-allele incursions, however the total number of avian Aallele sequences outnumbered B-allele sequences by over 3.5 to 1, and the relative rates of introduction were not significantly different across the two lineages suggesting no bias against avian B-allele NS segments entering mammalian hosts in nature. Therefore, this study provides evidence that avian B-allele NS genes are not attenuating in mammalian hosts and are able to cause severe disease. Thus, this lineage of IAV genes, previously assumed to be avian-restricted, should be considered when assessing zoonotic potential and pandemic risk of circulating avian IAVs.
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Sadewasser, Anne [Verfasser]. "Aktivitäten des Nichtstrukturproteins 1 bei der Vermehrung von Influenza B Virus in humanen Zellen / Anne Sadewasser." Berlin : Freie Universität Berlin, 2014. http://d-nb.info/1049189639/34.
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Goldman, Lea Nichole. "Kinetics and phenotype of the draining lymph node and pulmonary B cell response to an influenza A virus-like particle vaccine." Thesis, University of Iowa, 2013. https://ir.uiowa.edu/etd/4634.
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Influenza A virus (IAV) infection is a serious respiratory disease associated with significant morbidity and mortality worldwide. Annual vaccination is the most effective way to prevent infection and its potentially severe complications; however, the vaccines currently offered have several drawbacks that limit its availability and protective efficacy. Influenza virus-like particles (VLPs), which lack viral genetic material and are non-infectious, represent a promising vaccine candidate. Previous reports have shown VLPs are more immunogenic than subunit or recombinant proteins, and confer protection upon lethal challenge. A critical component of this protection is mediated by influenza HA-specific neutralizing Abs produced by memory B cells and plasma cells, the cellular products of the germinal center (GC) reaction. While preliminary studies have examined the humoral immune response to VLP vaccination, the current study is the first to characterize the GC response in secondary and tertiary lymphoid tissues. Mice were vaccinated with influenza VLPs using three immunization routes: subcutaneous (s.c.), intramuscular (i.m.), and intranasal (i.n.) and the GC response was assessed over time. Robust GC reactions were induced in the dLNs regardless of vaccination route, though the largest response was generated with VLPs s.c. The pattern of isotype expression was remarkably similar between routes, with IgM+ and IgG2+ B cells representing the majority of the GC B cell population. Mucosal immune responses in the upper (nasal) and lower (lung) airway were measured in mice vaccinated i.n. Marked GC reactions were induced in the nasal-associated lymphoid tissue (NALT), while the pulmonary response was relatively modest and short-lived compared to infection with IAV. Within the GC B cell population, IgM+ and IgG2+ B cells made up the majority, similar to the dLN response. Importantly, the pattern of isotype expression induced by VLPs mimicked the response induced by natural IAV infection, and suggests that VLPs contain the necessary innate immune agonists to induce a TH1 biased response.
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Dhenni, Rama B. S. "Role of Granzyme B in the Susceptibility to Secondary Bacterial Infection after Viral Infection." University of Cincinnati / OhioLINK, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1460446984.
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Kemdirim, Stella C. "Molecular cloning of the polymerase genes of influenza B virus : complete nucleotide sequence of the virus genome RNA segment encoding the PBI protein." Thesis, McGill University, 1986. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=65397.
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Zacharias, Zeb Ralph. "Induction and maintenance of diverse humoral and cellular immune responses following influenza A virus infection and vaccination." Diss., University of Iowa, 2018. https://ir.uiowa.edu/etd/6669.
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Influenza A virus (IAV) is a major cause of serious respiratory illness worldwide, leading to approximately 5 million severe cases and 500,000 deaths per year. Given the disease severity, associated economic costs, and recent appearance of novel IAV strains, there is a renewed interest in developing novel and efficacious “universal” IAV vaccination strategies as well as therapeutic remedies. Previous studies from our laboratory have concentrated on IAV-specific CD8 T cell-mediated protection against IAV infection as IAV-specific CD8 T cells are needed for efficient clearance of virus. Recent studies highlight that immunizations capable of generating local (i.e., nasal mucosa and lung) tissue-resident memory T and B cells in addition to systemic immunity offer the greatest protection against future IAV encounters. Current IAV vaccines are designed to largely stimulate IAV-specific antibodies, but do not generate the lung-resident memory T and B cells induced during IAV infections. In order to effectively generate lung-resident memory populations, it is believed a local antigen depot is needed as tissue-resident memory formation is enhanced by the presence of local antigen. Recently, polyanhydride nanoparticles have been demonstrated to slowly release their contents at the site of inoculation serving as an antigen depot. However, the ability of an intranasal vaccination with polyanhydride nanoparticles to induce IAV-specific lung-resident immune responses and provide protection against subsequent IAV infection has not been determined.
Here, I report on the intranasal administration of a biocompatible polyanhydride nanoparticle-based IAV vaccine (IAV-nanovax). IAV-nanovax is capable of providing protection against subsequent homologous and heterologous IAV infections in both inbred and outbred populations. My findings demonstrate that vaccination with IAV-nanovax promotes the induction of germinal center B cells within the lungs that are associated with both systemic IAV-specific IgG as well as local lung IAV-specific IgG and IgA antibodies. Furthermore, intranasal IAV-nanovax vaccination leads to a significant increase in IAV-specific CD4 and CD8 T cells within the lung vasculature as well as in the lung tissue. Most importantly, my studies demonstrate that IAV-nanovax induced lung-resident IAV-specific CD4 and CD8 T cells express canonical tissue-resident memory markers.
This dissertation further explores a novel regulation pathway previously identified by our laboratory where plasmacytoid dendritic cells (pDCs) eliminate IAV-specific CD8 T cells early during high-dose and high-pathogenic IAV infections in a FasL:Fas (pDCs:CD8 T cell) dependent manner. However, recent studies suggest that B cells are the predominate lymphocyte to express FasL in mice. Here, I demonstrate that FasLpos B cells greatly outnumber FasLpos pDC within the lung draining lymph nodes (dLNs) during IAV infections. Interestingly, my results demonstrate the presence of two subsets, CD11cpos and CD11cneg, of FasL-expressing B cells that differentially influence the IAV-specific CD8 T cell response during high-dose IAV infections. While CD11cneg B cells kill IAV-specific CD8 T cells, contributing to lethality during high-dose IAV infections, CD11cpos B cells may instead be protective.
In addition to the negative impacts of high-dose IAV infections, I also demonstrate that chronic ethanol (EtOH) consumption detrimentally impacts existing IAV-specific CD8 T cell memory responses. Here, my results reveal that chronic EtOH consumption causes a numerical loss in existing IAV-specific CD8 T cell memory responses. This numerical loss in existing IAV-specific CD8 T cell memory is associated with a reduction in cytotoxic activity within the lungs as well as an increase in morbidity and mortality during a secondary IAV challenge.
Together, the results presented herein demonstrate the ability of a novel polyanhydride nanovaccine to induce robust pulmonary IAV-specific T and B cell responses and further our understanding of factors that can negatively impact IAV-specific CD8 T cells as well as protection against IAV infection. Overall these findings highlight the importance of IAV-specific CD8 T cells, as well as CD4 T cells and B cells, in providing protection against IAV infections.
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Fage, Clément. "Étude de la résistance des virus influenza B contemporains aux inhibiteurs de la neuraminidase et son impact sur le fitness viral." Doctoral thesis, Université Laval, 2019. http://hdl.handle.net/20.500.11794/36444.
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Les virus influenza ont toujours eu un impact considérable sur l’humanité. Les virus influenza B (IB) ont longtemps été négligés et sous-estimés par rapport aux virus influenza A (IA). Ils ne représentent que 10 à 20% des infections annuelles par les virus influenza, mais peuvent devenir majoritaire certaines années et entrainer des symptômes similaires à ceux des virus IA. Les inhibiteurs de la neuraminidase (INA) sont les principaux traitements disponibles contre les virus influenza. Cependant, à la suite de mutations, certains virus influenza ont développé des mécanismes de résistance limitant dangereusement les options thérapeutiques. Actuellement, très peu de souches résistantes sont isolées en clinique car le fitness de ces virus résistants, c’est-à-dire leur capacité à se répliquer et se transmettre, est altéré. Or, il a été montré que des virus IA peuvent améliorer leur fitness et propager le phénotype de résistance. L’objectif de ce projet de thèse est de mieux comprendre la résistance des virus influenza B et son impact sur le fitness viral afin de mieux prévenir l’émergence de souches résistantes. Nous avons, dans un premier temps, étudié la résistance des virus influenza A et B au peramivir, le plus récent des INA. Nous avons confirmé que cette molécule est hautement active contre les souches saisonnières A et B. De plus, elle conserve une activité antivirale in vitro contre certaines souches virales ayant une sensibilité réduite ou hautement réduite contre d’autres INA (l’oseltamivir et le zanamivir). Dans un second temps, nous avons étudié le fitness de virus influenza B contemporains résistants in vitro et chez la souris. Nous avons montré que certains virus influenza B, ayant un phénotype de résistance croisée, peuvent maintenir un fitness similaire à celui du virus sauvage in vitro et in vivo. De plus, nous avons pu décrire et analyser un nouveau mécanisme de résistance chez les virus influenza B observé chez un cas clinique. Ces résultats soulignent la dangerosité de notre dépendance aux INA et nous encouragent à faire évoluer les stratégies thérapeutiques.
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Goka, Edward Anthony Chilongo. "Influenza A viruses dual and multiple infections with other respiratory viruses and risk of hospitalization and mortality." Thesis, University of Manchester, 2014. https://www.research.manchester.ac.uk/portal/en/theses/influenza-a-viruses-dual-and-multiple-infections-with-other-respiratory-viruses-and-risk-of-hospitalization-and-mortality(256eb122-a52a-4276-8dc1-28b5a2cc6662).html.
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Introduction: Epidemiological studies have indicated that 5-38% of influenza like illnesses (ILI) develop into severe disease due to, among others, factors such as; underlying chronic diseases, age, pregnancy, and viral mutations. There are suggestions that dual or multiple virus infections may affect disease severity. This study investigated the association between co-infection between influenza A viruses and other respiratory viruses and disease severity. Methodology: Datum for samples from North West England tested between January 2007 and June 2012 was analysed for patterns of co-infection between influenza A viruses and ten respiratory viruses. Risk of hospitalization to a general ward ICU or death in single versus mixed infections was assessed using multiple logistic regression models. Results: One or more viruses were identified in 37.8% (11,715/30,975) of samples, of which 10.4% (1,214) were mixed infections and 89.6% (10,501) were single infections. Among patients with influenza A(H1N1)pdm09, co-infections occurred in 4.7% (137⁄2,879) vs. 6.5% (59⁄902) in those with seasonal influenza A virus infection. In general, patients with mixed respiratory virus infections had a higher risk of admission to a general ward (OR: 1.43, 95% CI: 1.2 – 1.7, p = <0.0001) than those with a single infection. Co-infection between seasonal influenza A viruses and influenza B virus was associated with a significant increase in the risk of admission to ICU/ death (OR: 22.0, 95% CI: 2.21 – 219.8 p = 0.008). RSV/seasonal influenza A viruses co-infection also associated with increased risk but this was not statistically significant. For the pandemic influenza A(H1N1)pdm09 virus, RSV and AdV co-infection increased risk of hospitalization to a general ward, whereas Flu B increased risk of admission to ICU/ death, but none of these were statistically significant. Considering only single infections, RSV and hPIV1-3 increased risk of admission to a general ward (OR: 1.49, 95% CI: 1.28 – 1.73, p = <0.0001 and OR: 1.34, 95% CI: 1.003 – 1.8, p = 0.05) and admission to ICU/ death (OR: 1.5, 95% CI: 1.20 – 2.0, p = <0.0001 and OR: 1.60, 95% CI: 1.02 – 2.40, p = 0.04). Conclusion: Co-infection is a significant predictor of disease outcome; there is insufficient public health data on this subject as not all samples sent for investigation of respiratory virus infection are tested for all respiratory viruses. Integration of testing for respiratory viruses’ co-infections into routine clinical practice and R&D on integrated drugs and vaccines for influenza A&B, RSV, and AdV, and development of multi-target diagnostic tests is encouraged.
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Williams, Jonathan K., Alexander A. Shcherbakov, Jun Wang, and Mei Hong. "Protonation equilibria and pore-opening structure of the dual-histidine influenza B virus M2 transmembrane proton channel from solid-state NMR." AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC, 2017. http://hdl.handle.net/10150/626055.
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The influenza A and B viruses are the primary cause of seasonal flu epidemics. Common to both viruses is the M2 protein, a homotetrameric transmembrane proton channel that acidifies the virion after endocytosis. Although influenza A M2 (AM2) and B M2 (BM2) are functional analogs, they have little sequence homology, except for a conserved HXXXW motif, which is responsible for proton selectivity and channel gating. Importantly, BM2contains a second titratable histidine, His-27, in the tetrameric transmembrane domain that forms a reverse WXXXH motif with the gating tryptophan. To understand how His-27 affects the proton conduction property of BM2, we have used solid-state NMR to characterize the pH-dependent structure and dynamics of His-27. In cholesterol-containing lipid membranes mimicking the virus envelope, N-15 NMR spectra show that the His-27 tetrad protonates with higher pKa values than His-19, indicating that the solvent-accessible His-27 facilitates proton conduction of the channel by increasing the proton dissociation rates of His-19. AM2is inhibited by the amantadine class of antiviral drugs, whereas BM2 has no known inhibitors. Wemeasured the N-terminal interhelical separation of the BM2 channel using fluorinated Phe-5. The interhelical F-19-F-19 distances show a bimodal distribution of a short distance of 7 angstrom and a long distance of 15-20 angstrom, indicating that the phenylene rings do not block small-molecule entry into the channel pore. These results give insights into the lack of amantadine inhibition of BM2 and reveal structural diversities in this family of viral proton channels.
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Tissot, Alice. "Caractérisation Structurale et Biochimique de la Nucléoprotéine des virus grippaux de type A, B et D." Thesis, Université Grenoble Alpes (ComUE), 2017. http://www.theses.fr/2017GREAV014/document.
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Le virus de la grippe est un virus à ARN négatif appartenant à la famille des Orthomyxoviridae qui se compose de 7 membres dont les virus influenza A, B, C et D. Le génome viral comprend 7 à 8 particules ribonucléoprotéiques (RNP) au sein desquelles l’ARN viral (ARNv) est recouvert de multiples copies de nucléoprotéines (NP) et est associé à l’ARN polymérase virale via ses extrémités 3’ et 5’. Au cours de ce travail de thèse, nous nous sommes tout d’abord focalisés sur l’étude biochimique de NP A et NP B et avons pu mettre en évidence des comportements différents en ce qui concerne leurs propriétés d’oligomérisation en présence ou en absence d’ARN et en fonction de la concentration en sel. Pour la première fois nous avons pu observer une structure similaire aux RNP mais reconstituée uniquement à partir de NP A et d’un ARN de 12 nucléotides. Nous avons pu formuler l’hypothèse que 12 nucléotides de l’ARN serait fixés à la NP avec une forte affinité tandis que le reste de l’ARN fixerait la NP avec une affinité beaucoup plus faible. En parallèle nous avons résolu la structure cristallographique de la nucléoprotéine de la grippe de type D et réaliser la caractérisation de son interaction avec l’importine-α7 humaine. Enfin nous avons étudié la fixation de l’ARN sur NP D et mis en évidence l’importance de l’extrémité C-terminale dans le processus de fixation à l’ARN. Ces informations ont permis de formuler de nouvelles hypothèses quant au fonctionnement du virus de la grippe et permettre d’inscrire ce projet de thèse dans une dynamique globale de lutte contre ce virusInfluenza virus is a negative RNA virus belongs to the Orthomyxoviridae family which consists of 7 members including influenza viruses A, B, C and D. The viral genome comprises 7 to 8 ribonucleoprotein particles (RNP) in which the viral RNA (vRNA) is coated with multiple copies of nucleoproteins (NP) and is associated with the viral RNA polymerase by its 3 'and 5' ends. In this thesis, we first focused on the biochemical study of NP A and NP B and we demonstrate that there are different behaviors with regard to their oligomerization properties in the presence or absence of RNA and as a function of the salt concentration. For the first time we were able to observe a structure very similar to RNP which was reconstituted only from NP A and a 12 nucleotide RNA. Thus, we formulate the hypothesis that 12 nucleotides of the RNA would bind NP with a very strong affinity while the rest of the RNA would bind NP with a lower affinity. In parallel, we solved the crystallographic structure of the nucleoprotein of influenza D virus and we characterized its interaction with human importin-α7. Finally, we studied the binding of RNA on NP D and we demonstrated the importance of the C-terminal end in the RNA binding process. This thesis project made it possible to formulate new hypotheses concerning the functioning of the influenza virus and to include this thesis project in a global dynamic of combating the influenza virus
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Baumruck, Andreas [Verfasser], Alesia [Akademischer Betreuer] Tietze, and Harald [Akademischer Betreuer] Kolmar. "Chemical synthesis of membrane-associated peptides: A model study on influenza virus B protein BM2(1-51) / Andreas Baumruck ; Alesia Tietze, Harald Kolmar." Darmstadt : Universitäts- und Landesbibliothek Darmstadt, 2020. http://d-nb.info/1210644908/34.
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Baumruck, Andreas [Verfasser], Alesia Akademischer Betreuer] Tietze, and Harald [Akademischer Betreuer] [Kolmar. "Chemical synthesis of membrane-associated peptides: A model study on influenza virus B protein BM2(1-51) / Andreas Baumruck ; Alesia Tietze, Harald Kolmar." Darmstadt : Universitäts- und Landesbibliothek Darmstadt, 2020. http://d-nb.info/1210644908/34.
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Burmeister, Wilhelm Pascal. "Détermination de la structure de la neuraminidase du virus de la grippe B/Beijing/1/87 par cristallographie aux rayons X." Grenoble 1, 1992. http://www.theses.fr/1992GRE10138.
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Nous avons determine la structure de la neuraminidase du virus de la grippe souche b par la methode des derives lourds. Elle a ete affinee jusqu'a une resolution de 2. 2 a. La structure est tres similaire a celle de la neuraminidase des souches a. Deux sites de liaison de calcium, un sur l'axe d'ordre 4 du tetramere et un par sous-unite, ont ete identifies. Le premier site est capable de lier une variete de differents ions, comme l'analyse aux rayons x des cristaux dans lesquels nous avions fait diffuser des ions, l'a montre. Le deuxieme site montre toujours une pleine occupation par un ion calcium. La presence de calcium est necessaire a la stabilite de la neuraminidase. A basse concentration de calcium, on observe une denaturation irreversible qui depend de la temperature et de la concentration en calcium. L'etude cristallographique des complexes neuraminidase-acide sialique a revele les residus du site actif et leurs interactions avec l'acide sialique. L'acide sialique se trouve dans une conformation bateau contrairement a sa conformation chaise habituelle. En general, on observe une espece plane dans le site actif, qui a ete interpretee comme un ion oxocarbonium ou comme l'espece acide 2,3-dehydro-2-deoxy-n-acetyl neuraminique. Se basant sur cette observation, nous proposons un mecanisme d'action de la neuraminidase par distortion du substrat
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Gravel, Emilie. "Hepsine et matriptase activent l’hémagglutinine des virus influenza A et B et leur inhibition représente une nouvelle stratégie thérapeutique n’entraînant pas le développement de résistance." Mémoire, Université de Sherbrooke, 2016. http://hdl.handle.net/11143/9464.
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Résumé: Chaque année, les épidémies saisonnières d’influenza causent de 3 à 5 millions de cas sévères de maladie, entraînant entre 250 000 et 500 000 décès mondialement. Seulement deux classes d’antiviraux sont actuellement commercialisées pour traiter cette infection respiratoire : les inhibiteurs de la neuraminidase, tels que l’oseltamivir (Tamiflu) et les inhibiteurs du canal ionique M2 (adamantanes). Toutefois, leur utilisation est limitée par l’apparition rapide de résistance virale. Il est donc d’un grand intérêt de développer de nouvelles stratégies thérapeutiques pour le traitement de l’influenza. Le virus influenza dépend de l’activation de sa protéine de surface hémagglutinine (HA) pour être infectieux. L’activation a lieu par clivage protéolytique au sein d’une séquence d’acides aminés conservée. Ce clivage doit être effectué par une enzyme de l’hôte, étant donné que le génome du virus ne code pour aucune protéase. Pour les virus infectant l’humain, plusieurs études ont montré le potentiel de protéases à sérine transmembranaires de type II (TTSP) à promouvoir la réplication virale : TMPRSS2, TMPRSS4, HAT, MSPL, Desc1 et matriptase, identifiée récemment par notre équipe (Beaulieu, Gravel et al., 2013), activent l’HA des virus influenza A (principalement H1N1 et H3N2). Toutefois, il existe peu d’information sur le clivage de l’HA des virus influenza B, et seulement TMPRSS2 et HAT ont été identifiées comme étant capables d’activer ce type de virus. Les travaux de ce projet de maîtrise visaient à identifier d’autres TTSP pouvant activer l’HA de l’influenza B. L’efficacité de clivage par la matriptase, hepsine, HAT et Desc1 a été étudiée et comparée entre ces TTSP. Ces quatre protéases s’avèrent capables de cliver l’HA de l’influenza B in vitro. Cependant, seul le clivage par matriptase, hepsine et HAT promeut la réplication virale. De plus, ces TTSP peuvent aussi supporter la réplication de virus influenza A. Ainsi, l’utilisation d’un inhibiteur de TTSP, développé en collaboration avec notre laboratoire, permet de bloquer significativement la réplication virale dans les cellules épithéliales bronchiques humaines Calu-3. Cet inhibiteur se lie de façon covalente et lentement réversible au site actif de la TTSP par un mécanisme slow tight-binding. Puisque cet inhibiteur cible une composante de la cellule hôte, et non une protéine virale, il n’entraîne pas le développement de résistance après 15 passages des virus en présence de l’inhibiteur dans les cellules Calu-3. L’inhibition des TTSP activatrices d’HA dans le système respiratoire humain représente donc une nouvelle stratégie thérapeutique pouvant mener au développement d’antiviraux efficaces contre l’influenza.Abstract: Seasonal influenza epidemics cause between 3 and 5 millions severe cases of disease, leading to 250 000 to 500 000 deaths worldwide. Only two classes of drugs are currently available to treat influenza infections: neuraminidase inhibitors, such as oseltamivir (Tamiflu) and M2 channel inhibitors (adamantanes). However, the use of these antivirals is restricted by rapid emergence of viral resistance. It is therefore of great interest to develop new therapeutic strategies for the treatment of influenza disease. The influenza virus requires activation of its surface protein hemagglutinin (HA) to become infectious. This activation is achieved by proteolytic cleavage in a highly conserved amino acid sequence of the protein. Host cell proteases are responsible for this cleavage since the viral genome doesn’t encode any protease. For viruses that infect humans, many studies have shown the potential of type II transmembrane serine proteases (TTSP) to promote viral replication: TMPRSS2, TMPRSS4, HAT, MSPL, Desc1 and matriptase, recently identified by our team (Beaulieu, Gravel et al., 2013), activate HA of influenza A viruses (mainly H1N1 and H3N2). However, little is known about cleavage of influenza B virus HA, and only TMPRSS2 and HAT have been identified as being capable of activating this type of virus. This project aimed to identify other TTSPs able to activate influenza B HA. Cleavage efficacies of matriptase, hepsin, HAT and Desc1 were studied and compared. These four proteases were shown to be able to cleave influenza B HA using in vitro assays. However, only cleavage by matriptase, hepsin and HAT promoted viral replication. Moreover, these TTSPs also supported the replication of influenza A viruses. Thus, the use of a slow, tight-binding inhibitor (developed in collaboration with our laboratory) that binds to the TTSP active site, forming a covalent and reversible bond, significantly blocked viral replication in human bronchial epithelial Calu-3 cells. Since this inhibitor targets a host cell component, instead of a viral protein, viruses did not develop resistance after 15 passages in presence of the inhibitor in Calu-3 cells. Thus, inhibition of HA-activating TTSPs in the human respiratory tract represents a novel therapeutic strategy against influenza.
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Hestin, Marc. "Etude clinique de la grippe b : a propos de cinq observations." Université Louis Pasteur (Strasbourg) (1971-2008), 1987. http://www.theses.fr/1987STR1M263.
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YELSCH, PHILIPPE. "Influence des virus du sida sur les profils serologiques des sujets infectes par le virus de l'hepatite." Limoges, 1989. http://www.theses.fr/1989LIMO0177.
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Mäkelä, M. (Mira). "Influenssa A- ja B-virus sekä käytössä olevat influenssarokotteet ja kehitteillä olevat universaalit influenssarokotteet." Bachelor's thesis, University of Oulu, 2018. http://urn.fi/URN:NBN:fi:oulu-201804201511.
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Influenssa A- ja B-virukset ovat negatiivisäikeisiä RNA-viruksia, joiden genomi on segmentoitunut kahdeksaan osaan. Influenssa A-virus voidaan luokitella alatyyppeihin kalvoglykoproteiinien: hemagglutiniinin (HA) ja neuraminidaasin (NA) avulla. Influenssavirukset aiheuttavat kausittaisia epidemioita sekä ajoittain odottamattomia pandemioita. Kausi-influenssaepidemiat aiheutuvat kahdesta influenssa A-viruksen alatyypistä (H1N1 ja H3N2) sekä kahdesta influenssa B-viruksen linjasta (Yamagata ja Victoria). Influenssaviruksilta voi suojautua rokotteen avulla, jonka tehokkuus vaihtelee 60–90 % välillä. Tällä hetkellä käytössä olevia kausi-influenssarokotteita ovat trivalenttinen influenssarokote (TIV), LAIV-rokote sekä syksyllä 2018 Suomessa käyttöön otettava nelivalenttinen influenssarokote (QIV). Kehitteillä olevat universaalit influenssarokotteet pyrkivät antamaan mahdollisimman laajan ja kestävän suojan influenssaviruksia vastaan. Nämä universaalit influenssarokotteet ovat keskittyneet aktivoimaan spesifisten vasta-aineiden tuotantoa mm. HA:a, NA:a sekä M2-ionikanavia vastaan. Lisäksi kehitteillä on T-soluvastetta aktivoiva universaali influenssarokote.
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Przewlocki, Grzegorz. "Influence du murabutide sur la réponse immunitaire à des antigènes naturels et synthétiques du virus de l'hépatite B." Paris 6, 1986. http://www.theses.fr/1986PA066135.
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Eschlimann, Marine. "Influence de la variabilité des protéines d’enveloppe du virus de l’hépatite B sur l’évolution de l’infection évaluée par la persistance de l’antigène HBs." Thesis, Université de Lorraine, 2017. http://www.theses.fr/2017LORR0133/document.
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L’hépatite B chronique touche environ 257 millions de personnes dans le monde. La perte de l’antigène HBs (AgHBs), marqueur de guérison fonctionnelle, n’est que très rarement observée, même sous traitement antiviral (3-16 %). Les protéines d’enveloppe du virus de l’hépatite B (VHB), formant l’AgHBs, sont très variables et cruciales pour le pouvoir infectieux du virus de l’hépatite B (VHB) et la physiopathologie. Nous avons émis l’hypothèse que cette variabilité pourrait expliquer, au moins partiellement, l’évolution de l’infection par le VHB, évaluée par la clairance de l’AgHBs, chez des patients traités ou non par analogues nucléos(t)idiques anti-VHB. Chez 29 patients infectés par différents génotypes du VHB (A, C et D), présentant différents profils cliniques (infection aigüe ou chronique, co-infection VHB/VIH) et thérapeutiques, une très grande variabilité des protéines d’enveloppe du VHB a été mise en évidence. Chez ces patients, la persistance de l’AgHBs était corrélée avec la présence de mutations et délétions localisées dans des régions des protéines d’enveloppe virale jouant un rôle important dans la reconnaissance du virus par le système immunitaire. Ces résultats renforcent l’hypothèse que l’étude des protéines d’enveloppe du VHB pourrait mettre en évidence des signatures moléculaires influençant le fitness du VHB et par conséquent l’évolution clinique de la maladie liée à l’infection par le VHBChronic hepatitis B affects about 257 million people worldwide. The loss of HBS antigen (HBsAg), a marker of the functional cure, is very rarely observed, even on anti-HBV treatment (3-16%). The hepatitis B virus (HBV) envelope proteins (HBsAg) are highly variable and crucial for the viral infectivity and pathogeny. We hypothesized that the HBV variability in the envelope proteins could explain, at least partially, the evolution of HBV infection, evaluated by HBsAg clearance, in patients treated or not by anti-HBV nucleos(t)idic analogues. For 29 patients infected with different HBV genotypes (A, C and D), presenting different clinical profiles (acute or chronic infection, HBV/HIV co-infection) and therapies, a very high variability of HBV envelope proteins was observed. In these patients, the persistence of HBsAg was correlated with the presence of mutations and deletions located in areas that play a key role in the viral recognition by the immune system. These results reinforce the hypothesis that the study of HBV envelope proteins could highlight molecular signatures influencing HBV fitness which would subsequently modify the clinical evolution of HBV-related disease
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Finkernagel, Malin [Verfasser]. "Influence of vitamin D on the hepatitis B virus life cycle in different genotypes / Malin Finkernagel." Mainz : Universitätsbibliothek Mainz, 2017. http://d-nb.info/1124025464/34.
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Velay, Aurélie. "Influence des protéines d’enveloppe du virus de l’hépatite B sur la disparition de l’antigène HBs circulant lors du traitement de l’hépatite chronique B par analogues nucléos(t)idiques : mécanismes moléculaires impliqués et développement d’un traitement immunomodulateur à base d’anticorps monoclonaux." Thesis, Université de Lorraine, 2015. http://www.theses.fr/2015LORR0284/document.
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L'hépatite B chronique reste un problème majeur de santé publique. Sous traitement par analogues nucléos(t)idiques (NUCs), l'objectif thérapeutique ultime est la clairance de l'antigène (Ag) HBs. Nous avons étudié l'influence de la variabilité des protéines d'enveloppe, impliquées dans l'entrée cellulaire du virus et cibles de la réponse immune, sur la clairance de l'Ag HBs. Des patients traités par NUCs ayant obtenu une clairance de l'Ag HBs (resolvers) ont été appariés à des non-resolver. Deux mutations combinées sT125M/sP127T, caractéristiques des non-resolver, étaient associées à une baisse de l'antigénicité prédite. L'analyse par séquençage haut débit montrait une plus grande variabilité du gène S chez les non resolver. Des tests fonctionnels portant sur des particules virales mutées en sT125M et sP127T sont en cours. Ces données moléculaires sont en faveur de l'existence de "motifs" spécifiques dans le gène S associés à la persistance de l'Ag HBs sous traitement par NUCsHepatitis B virus (HBV)-related chronic infection remains difficult to eradicate. On treatment by nucleos(t)ide analogues (NUCs), HBs Antigen (Ag) clearance is the ultimate but difficult therapeutic goal. Our aim was to investigate how variability of HBV envelope protein, crucial in viral cellular entry and targeted by host immune response, could play a role in HBsAg clearance. HBV chronically infected patients, treated by NUCs with HBsAg clearance (resolver) were matched with patients without HBsAg clearance (non resolver). Combined mutations sT125M/sP127T, associated with HBsAg persistence, displayed a lower predicted antigenicity. Ultra Deep Sequencing of S gene showed a higher variability in non resolver. Functional assays on viral particles including sT125M and sP127T mutations versus reference particles are in progress. As a conclusion, molecular features observed in non NR argue in favor of a different pattern in HBV S characteristics according to variable NUCs efficiency
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Przewlocki, Grzegorz. "Influence du murabutide sur la réponse immunitaire à des antigènes naturels et synthétiques du virus de l'hépatite B." Grenoble 2 : ANRT, 1986. http://catalogue.bnf.fr/ark:/12148/cb37600494n.
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Mohr, Christina [Verfasser]. "Influence of hepatitis B virus surface protein variants associated with antiviral resistance on viral assembly and secretion of hepatitis B and hepatitis D viruses / Christina Mohr." Gießen : Universitätsbibliothek, 2014. http://d-nb.info/1068540001/34.
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Mohamed, Ajayeb Dakhelallah. "The influence of HLA in chronic hepatitis B and C and analysis of a new subtype of hepatitis C virus." Thesis, Imperial College London, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.243795.
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Sohlberg, Ebba. "Immune maturation in early childhood and the influence of herpesvirus infections." Doctoral thesis, Stockholms universitet, Institutionen för molekylär biovetenskap, Wenner-Grens institut, 2013. http://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-93034.
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The quality of immune responses develops from birth into adulthood and in the context of the host microbial environment. The aim of this work was to study immune maturation during childhood, and how this process can be affected by the common herpesviruses; Epstein-Barr virus (EBV) and cytomegalovirus (CMV). In paper I we studied monocytes, an important cell type for immunity in the newborn. We showed that the neonatal monocyte subsets exist in similar frequencies as adult subsets, and have a potent capacity for pro-inflammatory cytokine production. In paper II, III and IV we studied the effects of EBV and CMV infections on immune cell function in children. In paper II we found that monocyte-induced NK-cell production of IFN-γ, and plasma IFN-γ levels, were decreased in 2-year old EBV- and/or CMV-seropositive children and mostly so in co-infected children. In paper III we found that in 5-year old children, EBV and CMV co-infection was associated with the highest levels of differentiated NKG2C+ NK cells. CMV+ children had higher plasma IFN-γ and IL-15 levels and higher NK-cell cytotoxic capacity. In vitro PBMC systems showed elevated frequencies of NKG2C+ NK cells in the presence of EBV-infected cells. In paper IV we showed that a child’s age and subsequent capacity for anti-viral cytokine production affects in vitro EBV infection in terms of B-cell proliferation and B-cell acquisition of memory phenotype. PBMC from CMV+ children had lower EBV-induced accumulation of switched memory B cells, which was connected to high prevalence of CD57+CD8+ T cells and IFN-γ production. Taken together, this thesis work shows that monocyte subsets at birth can give potent functional responses and that latency with EBV and CMV has a significant effect on the differentiation process and functional capacity of anti-viral effector cells during childhood. This in turn could affect responses to related or unrelated infections or even to non-invasive antigens such as allergens.At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 3: Manuscript. Paper 4: Manuscript.
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Boudou, Valérie. "Synthèse et propriétés biologiques de Bêta-pentofurano-nucléosides de l'adénine d'énantiomérie non naturelle L : influence des substituants et des configurations en position(s) 2' et/ou 3'." Montpellier 2, 1997. http://www.theses.fr/1997MON20185.
Full textAbstract:
Afin de parvenir a de nouveaux composes antiviraux, plus actifs et moins toxiques que ceux actuellement utilises en clinique humaine, nous avons axe notre travail vers la synthese et l'etude d'analogues nucleosidiques de l'adenine, d'anomerie et d'enantiomerie non naturelle l. Le premier chapitre de cette these resume, a partir d'etudes bibliographiques, les proprietes biologiques de certains -l-nucleosides. Le second chapitre porte sur la synthese stereospecifique des quatre -l-pentofuranonucleosides de l'adenine, de leurs deux homologues 2'-desoxygenes et de la l-adenosine 5'-triphosphate. Le troisieme chapitre est consacre a la preparation de plusieurs derives inedits de la l-adenosine et de la 2'-desoxy-l-adenosine substitues en position 3' par un atome de fluor, un groupement azido ou un groupement amino. Les composes decrits dans ce memoire ont ete evalues en culture cellulaire vis-a-vis de divers virus, parmi lesquels celui de l'immunodeficience humaine (vih) et celui de l'hepatite b (vhb).
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Gómez, Basilio Rosario. "Respuesta a la vacuna del virus hepatitis B en pacientes en hemodialisis: influencia e importancia como factor pronóstico de morbilidad y mortalidad." Doctoral thesis, Universitat de Lleida, 1994. http://hdl.handle.net/10803/300299.
Full textAbstract:
El objetivo del estudio es poner de manifiesto en hemodializados un hecho demostrado en población general, la interrelación entre inmunidad y desnutrición.
El porcentaje de pacientes respondedores a la vacuna de Hepatitis B es 60.9%, similar a resultados de otros grupos e inferior a la obtenida en población normal a pesar de utilizar doble dosis. Este hecho expresa el déficit inmunitario existente en pacientes con insuficiencia renal crónica.
La desnutrición influye desfavorablemente en la respuesta a la vacuna del virus VHB, siendo los factores más estrechamente asociados la urea prehemodiálisis y la albúmina sérica.
La respuesta a la vacuna del virus VHB puede usarse como factor pronóstico de mortalidad y morbilidad en los pacientes hemodializados. Tras seguimiento de cuatro años la supervivencia en el grupo "respondedor" fue 20% superior que en el "no respondedor" y la diferencia de supervivencia fue estadísticamente significativa del "respondedor" para todos los períodos de seguimiento.
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Williams, John. "A mathematical model of the dynamics of hepatitis B virus transmission in the UK under the influence of different vaccination control strategies." Thesis, University of Oxford, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.298721.
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Barthel, Sebastian Robert [Verfasser], Eberhard [Akademischer Betreuer] [Gutachter] Hildt, and Robert [Akademischer Betreuer] [Gutachter] Tampé. "Influence of hepatitis B virus on insulin receptor signaling and liver regeneration / Sebastian Robert Barthel. Betreuer: Eberhard Hildt ; Robert Tampé. Gutachter: Robert Tampé ; Eberhard Hildt." Frankfurt am Main : Universitätsbibliothek Johann Christian Senckenberg, 2016. http://d-nb.info/1112601643/34.
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Stross, Leonhard Verfasser], Jörg [Akademischer Betreuer] Durner, and Ulrike [Akademischer Betreuer] [Protzer-Knolle. "The Influence of Regulatory T cells and other Immunoregulators on the Course of Hepatitis B Virus Infection / Leonhard Stross. Gutachter: Ulrike Protzer. Betreuer: Jörg Durner." München : Universitätsbibliothek der TU München, 2011. http://d-nb.info/1019588802/34.
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Chetaille, Bruno. "Facteurs pronostiques biopathologiques des lymphomes Hodgkiniens : influence du microenvironnement." Thesis, Aix-Marseille 2, 2010. http://www.theses.fr/2010AIX20666/document.
Full textAbstract:
Les lymphomes hodgkiniens(LH) représentent 30% des lymphomes. 90 % des patients en sont gueris mais parfois au prix d'importants effets secondaires(cancers secondaires notamment). L'enjeu actuel consiste à identifier les patients susceptibles de bénéficier d'une déescalade thérapeutique(même résultat thérapeutique obtenu au prix d'un traitement moins lourd)Actuellemnt les facteurs pronostiques utilisé en routine(stade Ann Arbor et index pronostic internationnal) ne permettent qu'une stratification imparfaite des patients notamment pour les stades localisés. Dans le but d'identifier de nouveaux facteurs pronostiques des LH nous avons mené une étude d'expression génétique sur puces Affimetrix. Nous identifions une signature moléculaire reliée à un bon pronostic et enrichie en gènes lymphocytaires B comprenant BCL11A, un facteur de transcription exprimé par les lymphocytes B et les cellules dendritiques plasmocytoïdes. Nous validons ce résultats en immunohistochimie sur TMA et retrouvons un meilleur pronostic associé aux tumeurs dont le microenvironnement est riche en cellules BCL11A+ et CD20+. Nous mettons également en évidence dans les cas EBV+ une signature d'expression génique enrichie en gènes caractéristiques d'une réponse immunitaire Th1 et anti-virale. Ces résultats peuvent fournir un rationnel scientifique à de nouvelle stratégies thérapeutiques. Il sera intéressant d'évaluer le bénéfice d'une déescalade thérapeutique chez les patients dont la tumeur présente un microenvironnement riche en lympocytesBThe outcome of classical Hodgkin lymphoma(cHL)patients may be related to the tumor microenvironment, which in turn may be influenced by Epstein-Barr virus(EBV)infection. To characterize the cHL microenvironment, a set of 63 cHL tissue samples was profiled using DNA microarrays. Their gene expression profile differed from that of histiocyte T-cell-richB-cell lymphoma(H/TCRBCL)samples that were used as controls, mainly du to high expression of PDCD1/PD-1 in H/TCRBCL. EBV-cHLtissues could be distinguished from EBV+samples by a gene signature characteristic ofTh1 and antiviral responses. Samples from cHL patients with favourable outcome overexpressed genes specific for B cells and genes involved in apoptotic pathways. An independent set of 146 cHL samples was analyzed using immunohistochemistry. It showed a significiant adverse value in case of high percentage of either TIA-1+-reactive cells or topoisomerase-2+tumor cells, whereas high numbers of BCL11A+, FOXP3+, or CD20+ reactive cells had a favorable influence. Our results suggest an antitumoral role for B cells in the cHL microenvironment and a stronger stromal influence of the strategies.120
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"Diversifying selective pressure on influenza B virus hemagglutinin." Thesis, 2009. http://hdl.handle.net/1911/61806.
Full textAbstract:
Influenza B virus hemagglutinin (HA) is a major surface glycoprotein with frequent amino-acid substitutions. However, the roles of antibody selection in the amino-acid substitutions of HA were still poorly understood. In order to gain insights into this important issue, an analysis was conducted on a total of 271 HA1 sequences of influenza B virus strains isolated during 1940∼2007. In this analysis, PAML (Phylogenetic Analysis by Maximum Likelihood) package was used to detect the existence of positive selection and to identify positively selected sites on HA1. Strikingly, all the positively selected sites were located in the four major epitopes (120-loop, 150-loop, 160-loop and 190-helix) of HA identified in previous studies, thus supporting a predominant role of antibody selection in HA evolution. Of particular significance is the involvement of the 120-loop in positive selection, which may become increasingly important in future field isolates. Despite the absence of different subtypes, influenza B virus HA continued to evolve into new sublineages, within which the four major epitopes were targeted selectively in positive selection. Thus, any newly emerging strains need to be placed in the context of their evolutionary history in order to understand and predict their epidemic potential.
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Jen, Hsiao Mei, and 蕭美人. "Genetic analysis of influenza B virus in Taiwan." Thesis, 2006. http://ndltd.ncl.edu.tw/handle/96979194996838060359.
Full textAbstract:
碩士長庚大學
醫學生物技術研究所
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The segmented genome of influenza B virus allows the exchange of gene segments between cocirculating strains of Victoria viruses and Yamagata viruses. Through the process of reassortment, diversity is generated by recombination of genes between viruses that differ in one or more gene segments. In this study, forty strains of influenza B virus were isolated and identified between 2000 and 2005. Throat swabs were collected from patients suffering from influenza B virus in medical centers in northern parts of Taiwan. To elucidate the molecular characteristics of these isolates, the analysis of HA, PB2, NA, M, and NS gene nucleotide sequences was performed. The Phylogenetic analysis of the HA1 gene sequences showed that 15 out of 40 strains were similar to B/Victoria/2/87-like viruses. The viruses were reassorted with the HA gene belonging to the B/Victoria/2/87 lineage and the NA gene belonging to the B/Yamagata/16/88 lineage, whereas both HA and NA genes of the other 25 strains were similar to B/Yamagata/16/88-like viruses belonged to the B/Yamagata/16/88 lineage. The clade of Taiwanese strains with high similarities to B/Taiwan/753/05, an expired case, was particularly detected by examination of the NS genes. Conclusively, influenza B virus is still prevalent in Taiwan and the accumulation of nucleotide mutations indicated that our isolates form a new cluster.
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Ni, Fengyun. "Functional and structural studies of influenza B virus hemagglutinin." Thesis, 2013. http://hdl.handle.net/1911/72014.
Full textAbstract:
Influenza A and B viruses are major causes of seasonal flu epidemics each year. Hemagglutinin (HA) mediates the binding of virus to host cell and the fusion with host membrane. The crystal of HA in complex with antibody that reveals the mechanism by which antibody recognizes HA may not diffract to high resolution, thereby preventing the accurate interpretation of the structural model. The application of normal mode refinement that aims for improving the structure quality at the low resolution is tested. These studies provide some guidelines for future refinement of HA-antibody complex structures. By comparing the residues constituting the base of the receptor binding site of influenza A and B virus HAs, it is found that they share some similarities, except for a Phe at position 95 of influenza B virus hemagglutinin (BHA) versus Tyr in of influenza A virus hemagglutinin (AHA). The recombinant protein BHA containing the F95Y mutation exhibits the increased receptor binding affinity and specificity. However, recombinant viruses with the Phe95Tyr mutation show lower erythrocyte agglutination titer and decreased binding abilities with different cell lines. The replication of the Phe95Tyr mutant virus in mice is also attenuated. These data suggest that the increased receptor binding ability of HA alone is not advantageous to the pathogenesis of the viruses. The structure of BHA2 (a portion of BHA near the C-terminus) at the post-fusion state has been determined to 2.45 Å resolution. This protein forms a hairpin-like conformation rich in -helices. About 70 residues from the N-terminus is a three-stranded coiled coil, and the remaining of the protein packs in anti-parallel against the groove formed by the central helices. In the post-fusion state of BHA2, the helix converted from the B-loop in pre-fusion state contacts the C-terminal fragment of this protein with more hydrophobic interactions as compared to AHA2. This structure illustrates the distinct stabilization strategy employed by BHA2 to form a post-fusion state that resembles that for AHA2. These studies will further the understanding of BHA with respect to its role in receptor binding ability and fusion.
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"The functional study of influenza B nucleoprotein." 2011. http://library.cuhk.edu.hk/record=b5894753.
Full textAbstract:
Lam, Ka Han.Thesis (M.Phil.)--Chinese University of Hong Kong, 2011.
Includes bibliographical references (leaves 77-82).
Abstracts in English and Chinese.
Acknowledgement --- p.ii
Abstract --- p.iii
摘要 --- p.v
Content --- p.vii
List of Abbreviations and Symbols --- p.xi
Chapter Chapter 1 --- Introduction
Chapter 1.1 --- Severity of influenza --- p.1
Chapter 1.2 --- Introduction of influenza viruses --- p.3
Chapter 1.2.1 --- Virion and genome structure --- p.4
Chapter 1.2.2 --- The replication cycle of influenza viruses --- p.5
Chapter 1.3 --- Influenza virus NP --- p.8
Chapter 1.3.1 --- The importance of NP in RNP structure maintenance --- p.9
Chapter 1.3.2 --- NP self oligomerization --- p.10
Chapter 1.3.3 --- NP-RNA interaction --- p.12
Chapter 1.3.4 --- NP and other interacting partners --- p.13
Chapter 1.4 --- Aim of the project --- p.16
Chapter Chapter 2 --- Materials and Methods
Chapter 2.1 --- Biological materials --- p.18
Chapter 2.2 --- Construction of NP mutants --- p.19
Chapter 2.3 --- Luciferase assay --- p.22
Chapter 2.4 --- Western blot --- p.23
Chapter 2.5 --- Protein expression and purification --- p.23
Chapter 2.6 --- Circular dichroism spectroscopy --- p.24
Chapter 2.7 --- Static Light scattering --- p.24
Chapter 2.8 --- Surface plasmon resonance --- p.25
Chapter 2.9 --- Co-immunoprecipitation (co-IP) --- p.26
Chapter Chapter 3 --- Identification of residues crucial for NPB oligomerization and ribonucleoprotein activity
Chapter 3.1 --- Introduction --- p.27
Chapter 3.2 --- Result --- p.31
Chapter 3.2.1 --- NPB mutants showed deficiency in overall transcription and replication activity --- p.31
Chapter 3.2.2 --- Expression and purification of NP mutants with low RNP activity --- p.37
Chapter 3.2.2.1 --- Expression of MBP-tagged NP variants --- p.37
Chapter 3.2.2.2 --- Purification of MBP-tagged NP variants --- p.38
Chapter 3.2.3 --- Secondary structures of NP variants were comparable t o wild type NP --- p.41
Chapter 3.2.4 --- NP variants with low RNP activity were abnormal in oligomerization in vitro --- p.42
Chapter 3.2.5 --- NP variants with low RNP activity were impaired in homo-oligomer formation in vivo --- p.45
Chapter 3.2.6 --- Discussion --- p.47
Chapter Chapter 4 --- Identification of residues crucial for NP 一 RNA interaction and ribonucleoprotein activity
Chapter 4.1 --- Introduction --- p.56
Chapter 4.2 --- Result --- p.58
Chapter 4.2.1 --- NPB mutants showed deficiency in overall transcription and replication activity --- p.58
Chapter 4.2.2 --- Expression and purification of NP variants with low RNP activity --- p.62
Chapter 4.2.3 --- Secondary structures of NP variants were comparable t o wild type NP --- p.63
Chapter 4.2.4 --- NP variants with low RNP activity were abnormal in RNA binding --- p.64
Chapter 4.3 --- Discussion --- p.68
Chapter Chapter 5 --- Conclusion and future prospect --- p.73
Copyright --- p.76
References --- p.77