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Host viral protein-protein interaction in influenza A virus infectionAlmutairi, Saeedah 24 July 2013 (has links)
Influenza A virus is well known for its severe clinical consequences. Structurally, this virus is made up of a lipid bilayer embedded with HA, NA and M2 proteins and a core containing eight viral ribonucleoprotein (RNP) complexes. In a typical RNP complex, the nucleoprotein binds with RNA in a non specific manner. The nucleoprotein plays a vital role in transcription, replication, and packaging of RNA during infection. This study aims that NP of A/PR/8/34(H1N1) virus and A/NY/55/2004(H3N2) virus interact with different host proteins depending on cell lines and virus strains. Monoclonal antibodies targeting the nucleoprotein of these viruses have been used for immunoprecipitation and the interacting proteins were identified by mass spectrometry. Tow proteins from the cytoplasm (elongation factor 1 sigma, and Mov10 protein) and 3 proteins from the nucleus (heat shock protein70, hnRNP K protein, and anti alpha actinin 4) were found in all the viral infected cells, and were chosen for validation study. This study will help to understand the virus-host interactions in a better way and may open the gateway for the synthesis of new antiviral drugs which can block these interactions, hence controlling the infection.
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Assessing the feasibility of swine influenza surveillance in ManitobaPasma, Timothy John 07 September 2011 (has links)
This project explored the feasibility of performing swine influenza surveillance in Manitoba using provincial veterinary diagnostic laboratory data and a farm premises identification registry. Diagnoses of swine influenza using polymerase chain reaction (PCR) were obtained from the veterinary laboratory database and linked with registry data on farm location and characteristics. Statistical and space-time analyses, including the Cuzick and Edwards test, Kulldorff Spatiotemporal scan, the Knox test and the modified CuSum method, were used to determine the time and spatial patterns of swine influenza in Manitoba. Analysis showed that swine influenza was endemic but also seasonal and that the frequency of diagnosis was increasing in time. Swine influenza was clustered in several regions across the province, including the southeast, and was clustered in time, particularly during the later time periods of the study. This study demonstrated that the farm premises identification registry is a crucial component of disease surveillance in animals.
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Designing Better Allocation Policies for Influenza VaccineDemirbilek, Mustafa January 2013 (has links)
Influenza has been one of the most infectious diseases for roughly 2400 years. The most effective way to prevent influenza outbreaks and eliminate their seasonal effects is vaccination. The distribution of influenza vaccine to various groups in the population becomes an important decision determining the effectiveness of vaccination for the entire population. We developed a simulation model using the Epifire C++ application program [2] to simulate influenza transmission under a given vaccination strategy. Our model can generate a network that can be configured with different degree distributions, transmission rates, number of nodes and edges, infection periods, and perform chain-binomial based simulation of SIR (Susceptible-Infectious-Recovered) disease transmission. Furthermore, we integrated NOMAD (Nonlinear Optimization by Mesh Adaptive Direct Search) for optimizing vaccine allocation to various age groups. We calibrate our model according to age specific attack rates from the 1918 pandemic. In our simulation model, we evaluate three different vaccine policies for 36 different scenarios and 1000 individuals: The policy of the Advisory Committee on Immunization Practices (ACIP), former recommendations of the Centers for Disease Control and Prevention (CDC), and new suggestions of the CDC. We derive the number of infected people at the end of each run and calculated the corresponding cost and years of life lost. As a result, we observe that optimized vaccine distribution ensures less infected people and years of life lost compared to the fore-mentioned policies in almost all cases. On the other hand, total costs for the policies are close to each other. Former CDC policy ensures slightly lower cost than other policies and our proposed in some cases.
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Host viral protein-protein interaction in influenza A virus infectionAlmutairi, Saeedah 24 July 2013 (has links)
Influenza A virus is well known for its severe clinical consequences. Structurally, this virus is made up of a lipid bilayer embedded with HA, NA and M2 proteins and a core containing eight viral ribonucleoprotein (RNP) complexes. In a typical RNP complex, the nucleoprotein binds with RNA in a non specific manner. The nucleoprotein plays a vital role in transcription, replication, and packaging of RNA during infection. This study aims that NP of A/PR/8/34(H1N1) virus and A/NY/55/2004(H3N2) virus interact with different host proteins depending on cell lines and virus strains. Monoclonal antibodies targeting the nucleoprotein of these viruses have been used for immunoprecipitation and the interacting proteins were identified by mass spectrometry. Tow proteins from the cytoplasm (elongation factor 1 sigma, and Mov10 protein) and 3 proteins from the nucleus (heat shock protein70, hnRNP K protein, and anti alpha actinin 4) were found in all the viral infected cells, and were chosen for validation study. This study will help to understand the virus-host interactions in a better way and may open the gateway for the synthesis of new antiviral drugs which can block these interactions, hence controlling the infection.
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175 |
Assessing the feasibility of swine influenza surveillance in ManitobaPasma, Timothy John 07 September 2011 (has links)
This project explored the feasibility of performing swine influenza surveillance in Manitoba using provincial veterinary diagnostic laboratory data and a farm premises identification registry. Diagnoses of swine influenza using polymerase chain reaction (PCR) were obtained from the veterinary laboratory database and linked with registry data on farm location and characteristics. Statistical and space-time analyses, including the Cuzick and Edwards test, Kulldorff Spatiotemporal scan, the Knox test and the modified CuSum method, were used to determine the time and spatial patterns of swine influenza in Manitoba. Analysis showed that swine influenza was endemic but also seasonal and that the frequency of diagnosis was increasing in time. Swine influenza was clustered in several regions across the province, including the southeast, and was clustered in time, particularly during the later time periods of the study. This study demonstrated that the farm premises identification registry is a crucial component of disease surveillance in animals.
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Influenza Virus H5N1 Non-structural Protein 1 Alters Interferon-alpha/beta SignalingJia, Danlin 12 February 2010 (has links)
Type I interferons (IFNs) function as the first line of defense against viral
infections by modulating numerous biological processes to establish an antiviral state and influencing the activation of various immune cells. During influenza A infection, the NS1 encoded by the virus genome disrupts many cellular processes to block type I IFN responses. We show that expression of H5N1 NS1 in HeLa cells reduces IFN-inducible activation of STAT proteins and its subsequent binding to DNA complexes. Subsequent analysis suggests NS1 blocks IFN signaling by inhibiting expression of type I IFN receptor subunit, IFNAR1, as well as up-regulating SOCS1 expression. Finally, we demonstrate that pretreatment of primary human lung tissue with IFN alfacon-1 inhibits H5N1 viral replication by up-regulating a number of interferon-stimulated genes. The data suggest that NS1 can directly interfere with Type I IFN signaling, and that pretreatment with IFN can inhibit H5N1 infection in primary human lung tissue.
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The Role of FKBP5 in Influenza Virus InfectionPak Kei, Chan 22 July 2010 (has links)
FK506 binding protein 5 (FKBP5) is a peptidyl propyl cis-trans isomerase that has been shown to interact with cellular immune pathways such as calcineurin and NF-κB. During an influenza infection, FKBP5 is up-regulated at the lung in an in vivo ferret infection model, yet the effect of FKBP5 on influenza replication and immune response is not understood. An in vitro model of human alveolar epithelial cell line A549 was established to study the cause and the function of FKBP5 up-regulation during an influenza infection. In this in vitro model, FKBP5 was not up-regulated by influenza replication, but instead it was up-regulated when A549 cells were treated with glucocorticoid. FKBP5 up-regulation did not have any effect on rate of influenza replication. However, FKBP5 up-regulation mediated the suppressive effect of glucocorticoid on pro-inflammatory cytokine production, since FKBP5 knock-down by siRNA increased cytokine production in the presence of glucocorticoid. Overall, the results suggested that the up-regulation of FKBP5 is a physiological response of lung cells to the increase of glucocorticoid during influenza infections, which facilitates the suppressive effect of glucocorticoid on pro-inflammatory cytokine production.
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Influenza Virus H5N1 Non-structural Protein 1 Alters Interferon-alpha/beta SignalingJia, Danlin 12 February 2010 (has links)
Type I interferons (IFNs) function as the first line of defense against viral
infections by modulating numerous biological processes to establish an antiviral state and influencing the activation of various immune cells. During influenza A infection, the NS1 encoded by the virus genome disrupts many cellular processes to block type I IFN responses. We show that expression of H5N1 NS1 in HeLa cells reduces IFN-inducible activation of STAT proteins and its subsequent binding to DNA complexes. Subsequent analysis suggests NS1 blocks IFN signaling by inhibiting expression of type I IFN receptor subunit, IFNAR1, as well as up-regulating SOCS1 expression. Finally, we demonstrate that pretreatment of primary human lung tissue with IFN alfacon-1 inhibits H5N1 viral replication by up-regulating a number of interferon-stimulated genes. The data suggest that NS1 can directly interfere with Type I IFN signaling, and that pretreatment with IFN can inhibit H5N1 infection in primary human lung tissue.
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The Role of FKBP5 in Influenza Virus InfectionPak Kei, Chan 22 July 2010 (has links)
FK506 binding protein 5 (FKBP5) is a peptidyl propyl cis-trans isomerase that has been shown to interact with cellular immune pathways such as calcineurin and NF-κB. During an influenza infection, FKBP5 is up-regulated at the lung in an in vivo ferret infection model, yet the effect of FKBP5 on influenza replication and immune response is not understood. An in vitro model of human alveolar epithelial cell line A549 was established to study the cause and the function of FKBP5 up-regulation during an influenza infection. In this in vitro model, FKBP5 was not up-regulated by influenza replication, but instead it was up-regulated when A549 cells were treated with glucocorticoid. FKBP5 up-regulation did not have any effect on rate of influenza replication. However, FKBP5 up-regulation mediated the suppressive effect of glucocorticoid on pro-inflammatory cytokine production, since FKBP5 knock-down by siRNA increased cytokine production in the presence of glucocorticoid. Overall, the results suggested that the up-regulation of FKBP5 is a physiological response of lung cells to the increase of glucocorticoid during influenza infections, which facilitates the suppressive effect of glucocorticoid on pro-inflammatory cytokine production.
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Self-evaluation on emergency preparedness for influenza pandemic by public health nurses in Hong Kong /Ma, Sau-mui, Rhoda. January 2007 (has links)
Thesis (M. Nurs.)--University of Hong Kong, 2007.
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