Le virus respiratoire syncytial (VRS) est le principal agent responsable desbronchopneumonies du jeune veau et des bronchiolites du nourrisson. Il n’existe pas devaccin ni d’antiviraux spécifiques pour l’homme. La réplication du génome et la transcriptiondes gènes viraux sont assurées par un ensemble de protéines virales constituant le complexeARN polymérase ARN-dépendant : la nucléoprotéine N, la phosphoprotéine P, le facteur detranscription M2-1 et la grosse sous-unité L. L’objectif principal de ma thèse était d’obtenirde nouvelles données structurales et fonctionnelles sur le complexe ARN-polymérase ARNdépendante(RdRp) du VRS, en particulier sur le couple P-L. Pour ceci j’ai tout d’aborddéveloppé un protocole de production et purification de la protéine L sous formerecombinante en cellules d’insecte. Ceci m’a permis ensuite de cartographier le sited’interaction de P avec L. J’ai ainsi mis en évidence que la protéine L interagit avec la partieC-terminale de la protéine P, au-niveau des résidus 216 à 239. Les données obtenuessuggèrent que ce domaine peut former un nouvel élément de reconnaissance moléculaire(« MoRE ») se structurant en hélice alpha lors de l’interaction avec la protéine L. De plus, lacartographie de ce domaine d’interaction m’a permis d’identifier entre les résidus 164 et 205de P une nouvelle région impliquée dans le recrutement de la protéine L aux corpsd’inclusions viraux. Ces nouvelles données ouvrent la voie à de nouvelles études structuralesde l’ARN-polymérase du VRS et nous permettent d’envisager de nouvelles stratégiesantivirales ciblant ce complexe. / Respiratory syncytial virus (RSV) is the leading cause of calves bronchopneumonia andinfants bronchiolitis. Neither vaccine nor antiviral treatments are currently available for use inhumans. Viral genome is replicated and transcribed by a set of viral proteins constituting theviral RNA-dependent RNA polymerase (RdRp) complex: the nucleoprotein (N), thephosphoprotein (P), the transcription factor (M2-1) and the large subunit (L). This workaimed to unveil new structural and functional data regarding the viral RdRp, especially the PLcouple. With this aim in view, I have first conceived a protocol to produce and purifyrecombinant L and P proteins expressed in insect cells. This tool enabled the fine mappingand characterization of the L binding domain of the RSV phosphoprotein. This highlightedthe interaction between the L protein and the C-terminal region of the P protein, especiallyresidues 216 to 239. Further data suggests that this area constitutes an alpha helix formingmolecular recognition element (« MoRE ») during P-L interaction. Furthermore, this studyunveiled a new region of the P protein encompassing residues 164 to 205, involved in therecruitment of L protein to viral inclusion bodies. These new results open the way toupcoming structural studies of RSV RdRp and allow us to define a new target for thedevelopment of antiviral drugs against RSV.

This retrospective cohort study examined risk factors associated with RSV-associated hospitalization (RSV-H) among infants born 32 to 35 weeks gestational age in Nova Scotia. Results were used to develop a clinical instrument (RSV-H scoring tool) that would discriminate between infants at high, moderate and low risk for RSV-H. Identifying the highest-risk infants, (using baseline information to predict RSV-H in the first year of life), would help target cost effective prophylaxis by Palivizumab (Pz), an expensive RSV-specific monoclonal antibody. Significant risk factors, determined by multivariate logistics, included infants born in December, January or February, passive household smoke exposure and household crowding. The scoring tool produced similar RSV-H post-test probabilities (3.1% pre-test probability) between risk groups (5.5% vs. 5.8%) and was unable to target highest risk infants. The tool could be used as an educational guideline for health professionals, outlining the importance of significant risk factors for RSV-H to parents and caregivers.

Thesis (Ph. D.)--University of Virginia, 2007. / Includes bibliographical references. Also available online through Digital Dissertations.

Sammanfattning Syfte: Att genom intervjuer beskriva sjukvårdspersonalens upplevelser och erfarenheter av att vårda och behandla spädbarn med respiratoriskt syncytial virus infektion (RSV) inom barnsjukvården på Gävle sjukhus samt att beskriva om vårdpersonalen utgick från aktuell evidens. Metod: Studien har en deskriptiv design där intervjuerna utfördes med semistrukturerade frågor på sex tillfrågade läkare samt sex tillfrågade barnsjuksköterskor som arbetade på barn och ungdomskliniken, Gävle sjukhus vid studiens utförande. Materialet bearbetades utifrån kvalitativ innehållsanalys. Resultat: I resultatet framkom fem huvudkategorier med fjorton underkategorier. Kategorierna beskriver när personalen uppfattades komma i kontakt med dessa spädbarn, hur de kategoriserades samt dess omvårdnadsmässiga och symptomatiska behandling. Underlag för vad som stödde behandlingen och omhändertagandet togs upp. Främsta problematiken upplevdes vara andningsbesvär och matproblematik. Behandlingsmässigt är det endast symptomatisk behandling som går att erbjuda. Omvårdnad i form av nutrition, andningsstöd samt lindrande och underlättande metoder var den behandling som utförs.  Diskussion: Vård och symptomatisk behandling av spädbarn med RSV bör ha stöd i senaste evidens för att inte orsaka mer lidande än vad som gynnar barnets bästa. God nutrition, vätska samt behandling med högflödesgrimma kan ses som de viktigaste aspekterna i denna behandling. Slutsats: Personalen beskrev likartat om hur spädbarn med RSV omhändertogs och behandlades. De flesta grundade sina vårdhandlingar i egna erfarenheter samt beprövade vedertagna metoder. Riktlinjer och evidensbaserad information nämndes som något man tror kan finnas men inget som någon hade använt sig av. Dock kunde man se att den vård som utfördes ändå följde många delar av den evidens som faktiskt finns. / Abstract Aim: The aim of this study was to describe, through interviews with healthcare professionals, how care and treatment of infants with respiratory syncytial virus (RSV) is applied in the pediatric care at Gävle hospital, as well as describing whether the healthcare staff were based there treatment on current evidence Method: The study has a descriptive design where the interviews were conducted with semi structured questions of six doctors and six pediatric nurses who was working in the pediatric clinics of Gävle hospital during this study. The material was processed based on qualitative content analysis. Result: The results showed five main categories with fourteen subcategories. The categories describe when the staff mostly met this kind of children and how they treat them during their hospital stay and how they recognized their symptoms, how they are categorized as well as their nursing and symptomatic treatment. Evidence of what they ground their treatment on was brought up. The main problem was breathing problems and nutrition problems. Treatment is only symptomatic treatment where nursing has a central focus. Nutrition, respiratory support and relieving and easing methods were the care given the infant. Discussion: The care and symptomatic treatment of infants with RSV should be supported in the latest evidence in order not to cause more suffering than benefits the child's best. Good nutrition, fluid, and Optiflow treatment can be seen as the most important aspects of this treatment. Conclusion: The staff was relatively united about how infant with RSV is handled and treated. Most of the parts based their care actions in own experiences and proven practices. Guidelines and evidence-based information where mentioned as something that they think may exist but nothing that anyone used. However, it was seen that many parts of the care performed follows the evidence that exist.

published_or_final_version / Medical Sciences / Master / Master of Medical Sciences

published_or_final_version / abstract / Paediatrics and Adolescent Medicine / Master / Master of Philosophy

Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal.

Reproduction de : Thèse d'exercice : Médecine vétérinaire : Toulouse 3 : 2007. / Titre provenant de l'écran titre. Bibliogr. p. 108-125.

Thesis (Ph. D.)--Oregon State University, 2010. / Printout. Includes bibliographical references (leaves 86-100). Also available on the World Wide Web.

Thesis (Ph. D.)--University of Virginia, 1999. / Spine title: RSV & CTL responses. Includes bibliographical references (p. 143-185). Also available online through Digital Dissertations.