Several members of the Flaviviridae family are major pathogens of humans including dengue (DEN), yellow fever (YF), tick-borne encephalitis (TBE), Murray valley encephalitis (MVE), Japanese encephalitis (JE), and hepatitis C virus (HCV). An Australian flavivirus Kunjin (KUN), however, appears to be naturally attenuated and does not cause an overt disease in humans. In contrast, genetically and antigenically closely related to KUN, New York strain of West Nile virus (NY WN) has already caused ~50 ....Several members of the Flaviviridae family are major pathogens of humans including dengue (DEN), yellow fever (YF), tick-borne encephalitis (TBE), Murray valley encephalitis (MVE), Japanese encephalitis (JE), and hepatitis C virus (HCV). An Australian flavivirus Kunjin (KUN), however, appears to be naturally attenuated and does not cause an overt disease in humans. In contrast, genetically and antigenically closely related to KUN, New York strain of West Nile virus (NY WN) has already caused ~500 deaths and over 20,000 registered infections since its emergence in North America in 1999, including 223 deaths and 9122 infections in 2003 alone. Recent studies with DEN indicated that flaviviruses may interfere with early steps of IFN-signalling pathway. The type I Interferon (IFN) response is the first line of defence against viral infections and many viruses have developed different strategies to counteract this response in order to ensure their survival in the infected host. In this grant we seek to exploit our extensive understanding of the molecular biology of KUN virus and the contrasting behaviour of KUN and NY WN viruses to gain an understanding of the role of flavivirus-mediated suppression of host anti-viral IFN response in virus-host relationships and its importance in determining virus virulence.Read moreRead less
Dengue Virus NS1 Protein As A Mediator Of Pathology
Funder
National Health and Medical Research Council
Funding Amount
$621,979.00
Summary
Dengue virus is an increasing problem in the tropical world, with estimated infection of more than 300 million people annually. Severe dengue disease can cause life-threatening bleeding and shock. Our project investigates the basis for the pathology of the disease. We have found that a viral protein termed NS1 binds to a receptor on immune cells and leads to production of inflammatory proteins which can promote vessel leakage. We will investigate drugs blocking this, in a disease model.
Novel Insights Into The Pathobiology Of Alphavirus Infections
Funder
National Health and Medical Research Council
Funding Amount
$827,660.00
Summary
Infections with mosquito-borne viruses are increasing at an alarming rate worldwide. Ross River virus is endemic in parts of Australia, PNG and Pacific islands, while chikungunya virus is distributed globally and causes recurrent pandemics that involve millions of people. These viruses cause severe musculoskeletal disease for several months after infection. This project aims to establish how these viruses interact with the human host to cause disease and may provide a basis for new treatments.
Needle Free Delivery Of Dengue And Zika Vaccines To The Skin
Funder
National Health and Medical Research Council
Funding Amount
$642,792.00
Summary
There is no Zika vaccine and only one licensed dengue vaccine, which is age and region restricted because of poor efficacy. We have developed safe subunit vaccine candidates capable of inducing potent virus neutralizing antibodies and demonstrated protection from lethal dengue challenge in a mouse model. Here we are partnering with Vaxxas to undertake preclinical development and GLP toxicity trials for microarray patches delivering dengue and zika virus subunit vaccines.
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.
Improving The Management Of An Emerging Viral Disease In Australia: Determination Of The Mechanisms Of Neuroinvasion By Hendra Virus And Their Control, Leading To Optimisation Of Post-exposure Therapy Following Contact With Hendra Virus
Funder
National Health and Medical Research Council
Funding Amount
$675,742.00
Summary
Hendra virus causes severe disease in people with >50% mortality; human infection is acquired following contact with affected horses. In nature, Hendra virus is carried by flying foxes and the cause of spill-over events to horses is unknown. The impact of Hendra virus on human health may rapidly increase in response to continued urban expansion; the outcome of this project will be improved decision support for those charged with the medical management of people exposed to this deadly virus.
A Glycomics Approach Towards Understanding Alphavirus Induced Inflammatory Disease And Discovering Novel Therapeutic Targets
Funder
National Health and Medical Research Council
Funding Amount
$316,449.00
Summary
Alphaviruses are transmitted by mosquitoes and cause a variety of serious human infections. This project investigates how alphaviruses cause disease, with special focus on inflammatory musculoskeletal diseases. The expected outcomes are a better understanding of human viral diseases, with a view to improving prevention and treatment strategies to reduce the disease burden of alphaviruses and related viruses. The research strategy is a world-first, and the institute is an international leader in ....Alphaviruses are transmitted by mosquitoes and cause a variety of serious human infections. This project investigates how alphaviruses cause disease, with special focus on inflammatory musculoskeletal diseases. The expected outcomes are a better understanding of human viral diseases, with a view to improving prevention and treatment strategies to reduce the disease burden of alphaviruses and related viruses. The research strategy is a world-first, and the institute is an international leader in this area.Read moreRead less
Host Metabolism And Responses Contributing To Flavivirus Replication And Pathogenesis
Funder
National Health and Medical Research Council
Funding Amount
$592,772.00
Summary
We aim to determine how viruses affect the cells they infect, In particular how they can alter the metabolism and balance of lipids in cells and how this impacts the bodies capability to respond immunologically. We believe that by understanding these basic principles we can target ares fr antiviral therapeutic potential.
Activation Of The Respiratory Syncytial Virus Fusion Protein
Funder
National Health and Medical Research Council
Funding Amount
$582,072.00
Summary
Respiratory Syncytial Virus (RSV) is the most important viral cause of respiratory tract disease in both infants and the elderly. However, there are few available options for control, whether by vaccination or therapeutic intervention. This proposal investigates the way RSV infects cells. A clearer understanding of the molecular basis of this process should provide potential targets for new drugs that can block this process and new insights for the generation of vaccine candidates.