Most viruses can infect only a reduced range of organisms and an effective replication is possible only in selected hosts. These hosts are called permissive for the virus. Molecular principles of a nonpermissiveness and viral mechanisms of overcoming replication obstacles are still not clearly elucidated. This thesis discusses the molecular causes of the cellular nonpermissiveness against a model retrovirus - Rous sarcoma virus. The research is conducted on duck cells which are semipermis- sive to the subgroup C of Rous sarcoma virus. The virus can enter those cells, but it is not able to produce enough infectious viral progeny. Two blocks of the viral replication cycle in the duck cells are described in the thesis. The first one is the probably not optimal cellular receptor recognition. The second one is in the late phase of the replication cycle when the viral proteins are synthesized. The amount of the envelope glyco- protein coding mRNA is reduced due to the altered splicing ratios, and the virions produced from the duck cells are less infectious. This block is recessive and can be partially omitted by cell fusions with permissive chicken cells; therefore, the block is not caused by specific restriction fac- tors in sensu stricto. Additionally, the influence of mutations in duck adapted Rous...

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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.

<p><strong>Background</strong>: Human rhinovirus/enterovirus (HRV/ENT) infections are commonly identified in children with acute respiratory infections (ARIs), but data on their clinical severity remains limited. We compared the clinical severity of HRV/ENT to respiratory syncytial virus (RSV), influenza A/B (FLU) and other common respiratory virus in children.</p> <p><strong>Methods</strong>: Retrospective study of children with ARIs and confirmed single positive viral infections on mid-turbinate swabs by molecular assays. Outcome measures included hospital admission and, for inpatients, a composite end-point consisting of intensive care admission, hospitalization greater than 5 days, oxygen requirements or death.</p> <p><strong>Results</strong>: A total of 116 HRV/ENT, 102 RSV, 99 FLU and 64 other common respiratory viruses were identified. Children with single HRV/ENT infections presented with significantly higher rates of underlying immunosuppressive conditions compared to those with RSV (37.9% vs 13.6%; p</p> <p><strong>Conclusions</strong>: Children with HRV/ENT had a more severe clinical course than those with RSV and FLUA/B infections and often had significant comorbidities. These findings emphasize the importance of considering HRV/ENT infection in children presenting with severe acute respiratory tract infections.</p> / Master of Science (MSc)

El objetivo de esta memoria se centra en primer lugar en la modelización del comportamiento de enfermedades estacionales mediante sistemas de ecuaciones diferenciales y en el estudio de las propiedades dinámicas tales como positividad, periocidad, estabilidad de las soluciones analíticas y la construcción de esquemas numéricos para las aproximaciones de las soluciones numéricas de sistemas de ecuaciones diferenciales de primer orden no lineales, los cuales modelan el comportamiento de enfermedades infecciosas estacionales tales como la transmisión del virus Respiratory Syncytial Virus (RSV). Se generalizan dos modelos matemáticos de enfermedades estacionales y se demuestran que tiene soluciones periódicas usando un Teorema de Coincidencia de Jean Mawhin. Para corroborar los resultados analíticos, se desarrollan esquemas numéricos usando las técnicas de diferencias finitas no estándar desarrolladas por Ronald Michens y el método de la transformada diferencial, los cuales permiten reproducir el comportamiento dinámico de las soluciones analíticas, tales como positividad y periocidad. Finalmente, las simulaciones numéricas se realizan usando los esquemas implementados y parámetros deducidos de datos clínicos De La Región de Valencia de personas infectadas con el virus RSV. Se confrontan con las que arrojan los métodos de Euler, Runge Kutta y la rutina de ODE45 de Matlab, verificándose mejores aproximaciones para tamaños de paso mayor a los que usan normalmente estos esquemas tradicionales. / Arenas Tawil, AJ. (2009). Mathematical modelling of virus RSV: qualitative properties, numerical solutions and validation for the case of the region of Valencia [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/8316