Genomic Analysis Of Host Response To Influenza A Infection
Funder
National Health and Medical Research Council
Funding Amount
$168,530.00
Summary
Influenza virus infects millions of people globally. However, it remains poorly understood why some infected individuals succumb to life threatening complications whilst others recovered relatively unaffected. This study use advance molecular technique to study influenza infection. It aims to identify the key steps in our immune systems that are progressively disrupted during influenza infection and how this process lead to a break down in our natural defence against the virus.
Assessment Of Interventions For Controlling Pandemic Influenza And Determining Data Needs To Inform These Assessments
Funder
National Health and Medical Research Council
Funding Amount
$183,040.00
Summary
The aim of this study is to help us prepare for a pandemic of influenza by comparing how effective the various available control strategies are at reducing transmission of the disease. The available control interventions include: reducing the number of close contacts we make with others, isolating cases after they are diagnosed, closing schools, quarantining households, quarantining individuals who are known to have been exposed to a case, and using antiviral drugs treat and protect people at ri ....The aim of this study is to help us prepare for a pandemic of influenza by comparing how effective the various available control strategies are at reducing transmission of the disease. The available control interventions include: reducing the number of close contacts we make with others, isolating cases after they are diagnosed, closing schools, quarantining households, quarantining individuals who are known to have been exposed to a case, and using antiviral drugs treat and protect people at risk of being infected. We will compare these control measures by taking due account of the ability and resources available for these interventions, and with regard to the need to maintain essential services. The comparisons will be made using mathematical models that describe the transmission of the infection. All available data and advice from experts will be used to ensure that realistic models are used for the comparisons. We will also use the models to determine the best use of the limited antiviral drugs available, until a vaccine becomes available. We will consider how the control strategy should be changed if a strain develops that is resistant to the antiviral drugs. In addition, we will determine what data need to be collected during the early stages of a pandemic to help us to determine the best use of the antiviral drugs, the best use of a new vaccine and to check on the development of resistance to the antiviral drugs.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.
Control Of Influenza A Virus Infection By Gamma Interferon-inducible Mediators
Funder
National Health and Medical Research Council
Funding Amount
$227,036.00
Summary
Influenza A virus is a cause of morbidity and mortality worldwide. Due to antigenic shift and drift of the virus, including the emergence of pandemic strains, humans are often challenged with strains different from those to which they have been exposed by vaccination or prior infection. This has historically resulted in very serious increases in illness and death. The most severe pandemic of influenza A virus that has occurred in modern times was the worldwide pandemic of 1918-1920 when over 20 ....Influenza A virus is a cause of morbidity and mortality worldwide. Due to antigenic shift and drift of the virus, including the emergence of pandemic strains, humans are often challenged with strains different from those to which they have been exposed by vaccination or prior infection. This has historically resulted in very serious increases in illness and death. The most severe pandemic of influenza A virus that has occurred in modern times was the worldwide pandemic of 1918-1920 when over 20 million deaths occurred. Development of new interventive strategies to combat virus-related illness therefore remains critical to complement the present vaccine approach. For this, a clear understanding of the host's response to influenza virus infection is essential. For its part, the immune system has at its disposal several strategies to combat influenza A virus. How the immune system deals with the virus is controlled by a complex network of interactions involving cells, cell surface molecules, soluble mediators termed cytokines and chemokines. One cytokine, interferon-gamma, seems to be a key player in the body s ability to get rid of the virus. Here, we are trying to understand how interferon-gamma does this. We believe that this cytokine causes specific immune cells to produce other molecules, such as indolamine 2,3-deoxygenase (IDO) and chemokines, and that it is these molecules that control virus growth. We do not know whether these molecules stop virus growth directly or by creating the right conditions for this. We are interested in understanding the sequence of events that is started by interferon-gamma and ends in the clearance of virus from the lungs. To study the immune response to influenza virus, we use a mouse model that reproduces most features of the human disease. By understanding the events that lead to effective virus clearance in this disease, it may be possible to design new ways in which to combat this problematic infection in humans.Read moreRead less
Regulation Of Antiviral And Antiinflammatory Responses By MTNF: Key Role Of Reverse Signaling By Host And Viral TNFR
Funder
National Health and Medical Research Council
Funding Amount
$568,501.00
Summary
New and re-emerging viral infections continue to pose a major problem. We have recently discovered a hitherto unrecognized process that the body uses to regulate its response to infection. Some viruses have evolved to target this process, underscoring its importance. We will study 2 virus models, poxvirus and influenza A, to understand how this process works during infection. We will also examine the potential to exploit this process to block pathology and influence recovery from infection.
Vitamin D And Acute Lower Respiratory Tract Infection (ALRI) In Indigenous Children
Funder
National Health and Medical Research Council
Funding Amount
$92,669.00
Summary
Australian Indigenous children experience extreme rates of acute lower respiratory infection (ALRI) that medical interventions have failed to reduce. Vitamin D is an important immunoregulatory molecule of the respiratory system that remains uncharacterised in this population. We propose that deficiency contributes to the persistent rates of ALRI. This study will characterise vitamin D levels in a cohort of Indigenous children with and without ALRI. The results will guide future intervention.
Preventing Illness And Death From Severe Influenza In Australia
Funder
National Health and Medical Research Council
Funding Amount
$1,719,110.00
Summary
Influenza and its complications are a common cause of hospitalisation and death. However, influenza is a moving target, with viruses constantly mutating from season to season. My research programme will transform the prevention and treatment of influenza and its complications by developing innovative public health and treatment strategies that can be applied globally. The work will optimise vaccine and treatment strategies to reduce illness and deaths from influenza.
The mortality rate from community-acquired pneumonia has not improved over the past four decades. New pulmonary infectious diseases such as due to non tuberculous mycobacteria are causing increasing problems and bronchiectasis is responsible for an ever increasing mortality, morbidity and economic burden on our health system. This grant will support Professor Waterer in continuing to reduce the personal and society burden of pulmonary infections.
Viral And Host Cell Gene Expression During The Establishment And Maintenance Phases Of Human Cytomegalovirus Latency
Funder
National Health and Medical Research Council
Funding Amount
$149,250.00
Summary
Human cytomegalovirus (CMV) is a herpesvirus which infects a majority of the population. HCMV is a significant cause of serious, life-threatening disease in neonates and in people who are immunosuppressed. Transplant recipients such as bone marrow, kidney and heart transplant patients are particularly at risk of developing CMV disease. Like other herpesviruses, after initial infection CMV can establish a life-long latent infection. During latency, the virus remains dormant in the human body and ....Human cytomegalovirus (CMV) is a herpesvirus which infects a majority of the population. HCMV is a significant cause of serious, life-threatening disease in neonates and in people who are immunosuppressed. Transplant recipients such as bone marrow, kidney and heart transplant patients are particularly at risk of developing CMV disease. Like other herpesviruses, after initial infection CMV can establish a life-long latent infection. During latency, the virus remains dormant in the human body and no infectious virus is made. However, when conditions are right the virus can awaken (ie reactivate) from its latent state, producing new infectious virus and disease. It is in immunosuppressed individuals such as transplant patients that viral latency and reactivation are of most medical concern, yet viral latency remains very poorly understood. The overall aim of these studies is to provide a much better understanding of how CMV latency is established and maintained, with the ultimate goal of making advances for the design of anti-viral therapies to disrupt these processes. This project has three major components: Firstly, we aim to identify and characterise viral gene expression during the establishment of latency and these findings will have profound implications to our understanding of latency. Secondly, we will examine how human cells are affected when they become latently infected. A new and exciting technology called DNA microarray now makes it possible to examine the expression of many thousands of genes in a single experiment. For the first time, we will be able to determine how the cell changes during the establishment and maintenance phases of latency. Thirdly, we will apply microarray technologies to determine how human cell genes are altered in response to the expression of individual viral genes that are active during the latent phase of infection.Read moreRead less