Identifying The Microbiological Risk Factors For Acute Lower Respiratory Infection In Indigenous Children To Inform Future Intervention Strategies
Funder
National Health and Medical Research Council
Funding Amount
$495,745.00
Summary
Lung infections such as pneumonia are common in Indigenous children, and can lead to repeated hospitalisation and permanent lung damage. They are also an important cause of preventable death in children. This study will look at the role of bacteria and viruses in lung infections, and will inform interventions to reduce the burden and consequences of lung infections in Indigenous children.
Exploring The Haemagglutinin-neuraminidase Of Human Parainfluenza Virus
Funder
National Health and Medical Research Council
Funding Amount
$731,268.00
Summary
Respiratory diseases, for example croup, in children are caused in the main by human parainfluenza viruses (hPIVs). No vaccines or specific antiviral therapy against hPIV infections exist. This project targets an essential protein in the virus’ lifecycle. This project will produce compounds that block the protein’s function and may provide drug candidates for development. Furthermore the role of human host cell-associated carbohydrates in parainfluenza infection will be better understood.
Inhibition Of IFN-?/? By Human Metapneumovirus And The Induction Of Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$605,251.00
Summary
The newly isolated human metapneumovirus (hMPV) causes significant respiratory illness in infants, young children and the elderly. The virus can persist long-term and may predispose individuals to chronic lung disease. This proposal aims to determine the mechanisms by which hMPV infection causes respiratory disease, with a view to improving treatments and preventing disease.
Role Of Toll-like Receptor 7 In Rhinovirus-induced Asthma Exacerbation
Funder
National Health and Medical Research Council
Funding Amount
$697,248.00
Summary
One third of the annual asthma-related health care expenditure may be attributable to asthma-related hospitalisations. Even mild asthmatics experience severe exacerbations at a rate of almost one per year1 and those attacks can be fatal. Rhinovirus (RV) causes the majority of asthma exacerbations which may be linked to an impaired antiviral interferon (IFN) response in asthmatics. RV is sensed by Toll-like receptor (TLR) 7, but the role of this innate host defence pathway in regulating antiviral
Asthma causes wheeze and shortness of breath via airway narrowing, with asthma attacks commonly caused by virus infections. We plan to investigate how airway narrowing during an asthma attack decreases the body’s ability to fight off a viral infection, causing prolonged infection, worse asthma symptoms, more airway inflammation and long-term damage within the airways. We will attempt to use current and novel treatments to reverse these problems, and improve treatment for asthma.
Effect Of Anti-IgE Antibody On Immune System Responses And Short-term Outcome In Acute Asthma In Children
Funder
National Health and Medical Research Council
Funding Amount
$571,752.00
Summary
We plan to undertake a randomised, double-blind, placebo-controlled, clinical trial of anti-IgE antibody given at the time of an acute attack of asthma in children aged 6-12 years. The idea for this arose from our own novel data – IgE levels increase with the most common infection causing acute asthma. Given evidence the virus uses IgE to cause inflammation, giving anti-IgE during the attack should reduce the severity of the attack and produce a new, effective treatment for acute asthma.
Investigation Into Host Susceptibility And Immune Responses In Young Children With Acute Wheezing Due To Human Rhinovirus Group C Infection
Funder
National Health and Medical Research Council
Funding Amount
$682,711.00
Summary
We recently made the surprising discovery that a new viral group, human rhinovirus group C (HRV-C), causes the majority of acute asthma in children. We also found that it causes half of the acute wheezing attacks in younger children, and is the only respiratory virus associated with allergy. So, HRV-C may be the key to the relationship between allergy and asthma. The planned project will focus on whether young children who wheeze with HRV-C have related defects in their immune system.
Protective memory T cell immune responses defend our body against pathogens by the rapid induction of killer T cells. This protects us from severe or perhaps even fatal disease. Our work will provide insights to how the body makes these potent ‘footsoldiers’. This work will have important implications for identifying how these immune cells can be manipulated to prevent and treat pathogenic and autoimmune disease and for optimising approaches to vaccination.
Rhinovirus Protease Subcellular Trafficking And Host Cell Targets; Relevance To Asthma Exacerbation And Vaccine Approaches
Funder
National Health and Medical Research Council
Funding Amount
$582,072.00
Summary
Rhinovirus (RV) infections are the major cause of virus induced asthma attacks, causing significant morbidity and mortality. Asthma & asthma exacerbations are increasing worldwide with new strategies urgently needed to reduce RV-associated disease. We aim to build on our substantive new data, using cutting edge technology to identify new targets for novel asthma therapies.
Identification Of Host Restriction Factors That Block Respiratory Virus Infection
Funder
National Health and Medical Research Council
Funding Amount
$956,898.00
Summary
Following inhalation, respiratory viruses can infect and grow in airway epithelial cells. Although immune cells such as macrophages are also susceptible to infection, this is generally abortive and new viruses are not released. This project will identify proteins induced in macrophages that block respiratory viruses and prevent their spread in the airways. We will also define mechanisms by which some virulent strains overcome this block to grow in macrophages.