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Burden Of Respiratory Infection In The First 2 Years Of Life: A Birth Cohort Study Of Emerging Respiratory Pathogens.
Funder
National Health and Medical Research Council
Funding Amount
$1,168,963.00
Summary
Respiratory illnesses are extremely common, but there is little information about patterns of infection in the community using modern diagnostic tests. Children have the highest rates of infection and transmit to all other age groups. We intend to recruit 138 newborns to monitor respiratory symptoms and collect specimens for testing in the first two years of life. This will allow us to document illnesses due to known and newly identified respiratory pathogens.
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.
Soluble Inhibitors Of Influenza Virus In The Airway Fluids Of Mice, Ferrets And Humans.
Funder
National Health and Medical Research Council
Funding Amount
$404,803.00
Summary
This study will characterize the ability of soluble proteins in airway secretions to recognize and destroy influenza viruses. As many of our insights regarding influenza pathogenesis are derived from studies in animal models, we will characterize the importance of proteins in airway fluids from mice and ferrets, as well as from humans. These findings will be of particular importance when assessing the relevance of particular animal models to understanding human disease.
Development Of National Protocols For The Detection Of Influenza A H5N1
Funder
National Health and Medical Research Council
Funding Amount
$248,229.00
Summary
This project will develop a best practice approach to the diagnosis of influenza A H5N1 (Bird Flu) in Australian public health laboratories. Tests such as reverse transcription polymerase chain reaction (RT-PCR) are in use globally for influenza A H5N1 detection. Some proprietary rapid influenza A tests also claim to detect influenza A H5N1. However there is little information on systematic evaluation of these, largely because there have been relatively few human influenza A H5N1 cases and patie ....This project will develop a best practice approach to the diagnosis of influenza A H5N1 (Bird Flu) in Australian public health laboratories. Tests such as reverse transcription polymerase chain reaction (RT-PCR) are in use globally for influenza A H5N1 detection. Some proprietary rapid influenza A tests also claim to detect influenza A H5N1. However there is little information on systematic evaluation of these, largely because there have been relatively few human influenza A H5N1 cases and patient specimens. Australian laboratories need authoritative guidelines as to optimal influenza tests, target genes and reagents. Development of a simple, potentially automated type specific test for influenza A H5N1 antibody such as enzyme immunoassay (EIA) is also desirable, as widely used tests cannot distinguish between infection with H5 or other influenza types. Reference methods such as haemagglutination inhibition (HAI) are cumbersome. In this project mock specimens for virus and antibody detection will be created using viral cell culture and infected chicken derived influenza A H5N1. This will be undertaken in physical containment level 4 (PC4) facilities in Australia's designated human and animal PC4 laboratories. This material will be used for (i) specimen panels to compare the performance of candidate laboratory tests (ii) positive control material in all tests undertaken and (iii) quality assurance exercises to ensure high standards of testing. Using these panels the group will assess influenza H5N1 RT-PCR, tests for detection of influenza proteins including immunofluorescence, and rapid point of care influenza A detection tests available in Australia. An EIA method currently used to detect influenza antibodies from different animal species will be refined to develop a simple test for type specific detection influenza A H5N1 antibodies, and subsequently evaluated using animal sera. A standard method for HAI reference serology for use in public health laboratories will also be recommended, and the best approaches to high throughput automated RT-PCR, and performing RT-PCR in the field on portable instrumentation will be explored. Recommendations for standard protocols for influenza A H5N1 will be developed and will submitted for review and endorsement by Commonwealth ministerial advisory committees.Read moreRead less
CHARACTERISATION OF NOVEL PICORNAVIRUS-LIKE VIRUSES IDENTIFIED FROM PATIENTS WITH ACUTE RESPIRATORY INFECTIONS.
Funder
National Health and Medical Research Council
Funding Amount
$366,998.00
Summary
The common cold and serious chest colds are usually due to viral infections, and mostly occur in children. Unfortunately we can only be certain of the virus causing this illness in as little as 15% of cases. We intend to address this lack of research by examining, in detail, a new virus we recently identified in a child with serious respiratory illness that required admission to hospital. Testing by our laboratory suggests that the new virus is related to picornaviruses (which cause some common ....The common cold and serious chest colds are usually due to viral infections, and mostly occur in children. Unfortunately we can only be certain of the virus causing this illness in as little as 15% of cases. We intend to address this lack of research by examining, in detail, a new virus we recently identified in a child with serious respiratory illness that required admission to hospital. Testing by our laboratory suggests that the new virus is related to picornaviruses (which cause some common colds) but seems to be present in children with far more serious illness. Our study plans to more completely identify the new picornavirus-like virus (PLV) using the tools of molecular biology and the expertise of a senior team of Australian scientists and clinicians who have recently made several virus discoveries in Australia, demonstrating that Australian virus research is capable of achieving highly competitive results that benefit our hospitals and especially their young patients. Our studies will develop extremely sensitive tests which rely on the detection of very small amounts of the viral genome. We can use these tests to determine what the whole virus looks like, when it might occur during the year and whether the PLV are found worldwide. Our studies will also produce viral proteins in the laboratory and use these to make new tests for stored blood samples. If a blood sample comes from a patient who has previously been infected by PLV, their blood will contain specific antibodies which we will then be able to detect. We also intend to determine whether some strains of PLV are more or less likely to cause serious illness than others. Improved understanding of these and other viruses minimises the chance of illness spreading within a hospital, helps scientists to decide against which viruses to design vaccines and drugs and aids medical doctors to better identify what once went undiagnosed.Read moreRead less
Influenza A Virus PB1-F2 Protein: A Putative Virulence Factor And Initiator Of Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$474,718.00
Summary
Influenza virus produces a protein of undefined function called PB1-F2. Infection of mice with virus expressing PB1-F2 from virulent strains causes severe lung inflammation, while PB1-F2 from milder seasonal viruses does not. We will examine how PB1-F2 influences virulence of human influenza in the ferret, which exhibits the same illness as humans. This work will help understand the disease severity of newly evolved influenza viruses of humans and the role of PB1-F2 in mediating this.
The Role Of Noncoding Viral RNAs In Flavivirus Infection And Exosomal Signalling
Funder
National Health and Medical Research Council
Funding Amount
$683,447.00
Summary
The application is aimed at investigating the novel role for viral noncoding RNAs in exosomal antiviral signalling and associated outcome of infection with West Nile virus. We will identify host enzymes involved in generation of viral noncoding RNAs, determine which host proteins they interact with and how these interactions determine their incorporation into secreted exosomes to influence outcome of infection.
Use Of Mouse Models To Study Mechanisms Of Pathology In Viral Exacerbations Of COPD
Funder
National Health and Medical Research Council
Funding Amount
$411,960.00
Summary
We want to understand why cigarette smoke exposure worsens respiratory virus infections. People who smoke, or who have smoked in the past, or who are exposed to environmental (passive) smoke, get sicker than nonsmokers when they get a respiratory virus infection, such as a common cold or the flu. This is true for people of all age groups, but we don't know why smoke has this effect. We think it may be because smoke interferes with some aspects of the immune response. A particular focus of our re ....We want to understand why cigarette smoke exposure worsens respiratory virus infections. People who smoke, or who have smoked in the past, or who are exposed to environmental (passive) smoke, get sicker than nonsmokers when they get a respiratory virus infection, such as a common cold or the flu. This is true for people of all age groups, but we don't know why smoke has this effect. We think it may be because smoke interferes with some aspects of the immune response. A particular focus of our research is chronic obstructive pulmonary disease. COPD is a serious lung disease which generally occurs in people who have smoked for many years. However, many COPD patients stopped smoking many years ago. COPD patients are especialy at risk of serious outcomes if they get a respiratory infection (known as an acute COPD exacerbation) and patients with COPD exacerbations use a lot of health care resources. There are no effective drugs to prevent or treat COPD exacerbations. We are currently using a mouse model of smoke exposure and virus infection to do this research, which is a much faster and more ethical approach than using humans in research. We believe that we will get a better understanding of how smoke affects the immune response to infection. This is likely to contribute to the development of better drugs for COPD exacerbations and other types of smoking related lung disease.Read moreRead less
Understanding How Cytomegaloviruses Establish Systemic Infection
Funder
National Health and Medical Research Council
Funding Amount
$668,144.00
Summary
Human cytomegalovirus (HCMV) infects most Australians, causes birth defects and harms transplant patients. Vaccines against it have worked poorly. HCMV spreads throughout the body and is never cleared. To control infection we must identify its key checkpoints. Using mouse CMV, we find that host dendritic cells, which normally defend against infections, are taken over and spread virus to new sites. The viral gene responsible is a potential target for intervention. We will define how it works.