The effect of pandemic influenza H1N1 viral infection on house dust mite sensitized mice
department or school: Medicine, Faculty of
department or school: Medicine, Department of
data provider: DSpace
degree campus: UBCV
creator: Chen, Hao Hang Rachel
issued: 2016-07-14T20:13:22Z
issued: 2016
related degree: Master of Science - MSc
degree grantor: University of British Columbia
description: A disproportionately large number of asthmatics experienced morbidity and mortality during the 2009 H1N1 pandemic. To date, there is little information on the mechanisms behind this epidemiological and clinical observation. Using a murine asthma model, we sought to determine the effects of airway inflammation on host responses to pandemic H1N1 (pH1N1) infection. We hypothesized that mice with an allergic airway phenotype would have a greater viral susceptibility to pH1N1 infection and a dysregulated host response that prevents effective viral clearance and leads to increased burden of pulmonary inflammation, resulting in poor clinical outcomes. We established a murine allergic airway model using house dust mite (HDM) extract. We intranasally instilled male BALB/c mice with HDM or sham PBS daily for two weeks; after which we introduced a single intranasal dose of pH1N1 virus or control vehicle fluid (CAF). HDM or PBS instillation continued daily post-viral infection (pi) forming four groups: 1) sham-sensitized + CAF, 2) HDM-sensitized + CAF, 3) sham-sensitized + pH1N1, and 4) HDM-sensitized + pH1N1. Mice were weighed daily. Virus-infected animals were euthanized at 1-hr pi and on Day 1, 2, 4, 5, 6, and 8 pi and non-infected animals were euthanized on Day 0 and 8 pi. Viral titre, interferon-β (IFN β), and interferon-stimulated gene (ISG) expression patterns were determined by qPCR on RNA extracted from homogenized lung tissue. IFN β protein levels were evaluated by ELISA in bronchoalveolar lavage. Pulmonary inflammation was quantified using H&E stain on formalin-fixed paraffin-embedded lung tissue. HDM-sensitized animals exhibited significantly greater weight loss than sham-sensitized animals following infection. Also, HDM-sensitized mice had significantly higher viral titres on Day 8 pi as compared to sham-sensitized mice. Downstream ISG inductions were dampened in HDM-sensitized, virus-infected animals despite comparable initial IFN β response in HDM- and sham-sensi…
aggregated CHO: https://circle.library.ubc.ca/rest/handle/2429/58438
note: THE EFFECT OF PANDEMIC INFLUENZA H1N1 VIRAL INFECTION ON HOUSE DUST MITE SENSITIZED MICE by Hao Hang Rachel Chen B.Sc. (Honours), Queen’s University, 2013 A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF MASTER OF SCIENCE in THE FACULTY OF GRADUATE AND POSTDOCTORAL STUDIES (Experimental Medicine) THE UNIVERSITY OF BRITISH COLUMBIA (Vancouver) July 2016 © Hao Hang Rachel Chen, 2016 ii Abstract A disproportionately large number of asthmatics experienced morbidity and mortality during the 2009 H1N1 pandemic. To date, there is little information on the mechanisms behind this epidemiological and clinical observation. Using a murine asthma model, we sought to determine the effects of airway inflammation on host responses to pandemic H1N1 (pH1N1) infection. We hypothesized that mice with an allergic airway phenotype would have a greater viral susceptibility to pH1N1 infection and a dysregulated host response that prevents effective viral clearance and leads to increased burden of pulmonary inflammation, resulting in poor clinical outcomes. We established a murine allergic airway model using house dust mite (HDM) extract. We intranasally instilled male BALB/c mice with HDM or sham PBS daily for two weeks; after which we introduced a single intranasal dose of pH1N1 virus or control vehicle fluid (CAF). HDM or PBS instillation continued daily post-viral infection (pi) forming four groups: 1) sham-sensitized + CAF, 2) HDM-sensitized + CAF, 3) sham-sensitized + pH1N1, and 4) HDM-sensitized + pH1N1. Mice were weighed daily. Virus-infected animals were euthanized at 1-hr pi and on Day 1, 2, 4, 5, 6, and 8 pi and non-infected animals were euthanized on Day 0 and 8 pi. Viral titre, interferon-β (IFN β), and interferon-stimulated gene (ISG) expression patterns were determined by qPCR on RNA extracted from homogenized lung tissue. IFN β protein levels were evaluated by ELISA in bronchoalveolar lavage. Pulmonary inflammation was quantified using H&E stai…
has type: Thesis/Dissertation
date issued: 2016-09
is shown at: 10.14288/1.0305867
language: eng
degree discipline: Experimental Medicine
provider: Vancouver : University of British Columbia Library
publisher: University of British Columbia
rights: Attribution-NonCommercial-NoDerivatives 4.0 International
rights URI: http://creativecommons.org/licenses/by-nc-nd/4.0/
scholar level: Graduate
type: Text
identifier URI: http://hdl.handle.net/2429/58438