The dynamics of viral latency in chronic infection. Although many acute infections can now be controlled, we still suffer from a large number of chronic infections such as HIV or herpes that cannot be eradicated. Many of these infections persist because they can lie dormant in a 'latent' state. How this latent state is established, and how long it lasts are important to understand if we want to control these infections. We have assembled a team of mathematicians, immunologists and virologists in ....The dynamics of viral latency in chronic infection. Although many acute infections can now be controlled, we still suffer from a large number of chronic infections such as HIV or herpes that cannot be eradicated. Many of these infections persist because they can lie dormant in a 'latent' state. How this latent state is established, and how long it lasts are important to understand if we want to control these infections. We have assembled a team of mathematicians, immunologists and virologists in order to study latent infection at the cellular level, and within infected monkeys. This will provide the first insights into the dynamics of latency - how these cells are produced and die - and should lead to novel approaches to controlling chronic infection.Read moreRead less
Norovirus Infection At The Stress Granule-PKR-p-elF2α Axis
Funder
National Health and Medical Research Council
Funding Amount
$505,967.00
Summary
This project application will aim to investigate and understand how viruses that cause vomiting and diarrhoea are able to infect, proliferate and spread within the human body. It aims to address how viruses are able to avoid and replicate in the presence of an effective immune response. We have evidence showing that Noroviruses are able to exploit certain antiviral proteins to paradoxically aid in virus replication and survival.
Developing mathematical models of infection and transmission to link biology, epidemiology and public health policy. Infectious diseases constitute a significant burden on the health of the population. Understanding how best to control them requires a multi-faceted approach, combining data from biology, medicine and population health with mathematical and computational models of disease transmission. This project will investigate the "flu" and other diseases.
Discovery of Novel Respiratory Viruses Causing Influenza-Like Illness in Healthy Australian Adults Aged 18 to 64 Years. This work will inform our understanding of the causes of acute respiratory illnesses in Australia at the present time by looking for both known and previously undiscovered respiratory viruses. Increasing the knowledge base regarding causes of disease will have downstream relevance for health policy planners seeking to assess the burden of disease due to different causes. Early ....Discovery of Novel Respiratory Viruses Causing Influenza-Like Illness in Healthy Australian Adults Aged 18 to 64 Years. This work will inform our understanding of the causes of acute respiratory illnesses in Australia at the present time by looking for both known and previously undiscovered respiratory viruses. Increasing the knowledge base regarding causes of disease will have downstream relevance for health policy planners seeking to assess the burden of disease due to different causes. Early identification and description of new diseases will allow pre-emptive evaluation of new public health threats. This information will help to ensure availability and marketability of vaccines to prevent infection.Read moreRead less
Structure-based discovery of anti-rotaviral agents. Rotavirus causes, particularly in children under 5 years of age, significant loss of life worldwide. Over 600,000 children under 5 years of age per annum die as a result of rotavirus infection. Australia records over 10,000 hospitalisations per annum due to rotavirus infection. This project aims, using structure-based drug design techniques, to develop inhibitors of a rotavirus protein that is essential in its lifecycle. These inhibitors may ....Structure-based discovery of anti-rotaviral agents. Rotavirus causes, particularly in children under 5 years of age, significant loss of life worldwide. Over 600,000 children under 5 years of age per annum die as a result of rotavirus infection. Australia records over 10,000 hospitalisations per annum due to rotavirus infection. This project aims, using structure-based drug design techniques, to develop inhibitors of a rotavirus protein that is essential in its lifecycle. These inhibitors may lead to the development of useful drugs to treat rotavirus infection and may reduce significant loss of life caused by this deadly virus.Read moreRead less
Novel target of amiloride analogues - picornaviral RNA polymerase. Picornaviruses cause a range of diseases such as poliomyelitis, meningitis, myocarditis, hepatitis A, neonatal sepsis and common cold. No antiviral treatment is available for these infections. Nearly 50% of antiviral drugs used in medicine are viral polymerase inhibitors; however picornaviral RNA polymerase has been largely overlooked as a drug target. We have discovered a group of compounds that inhibit picornaviral RNA polymera ....Novel target of amiloride analogues - picornaviral RNA polymerase. Picornaviruses cause a range of diseases such as poliomyelitis, meningitis, myocarditis, hepatitis A, neonatal sepsis and common cold. No antiviral treatment is available for these infections. Nearly 50% of antiviral drugs used in medicine are viral polymerase inhibitors; however picornaviral RNA polymerase has been largely overlooked as a drug target. We have discovered a group of compounds that inhibit picornaviral RNA polymerase. This project aims to define the inhibition mechanism and to evaluate a potential use of these compounds for antiviral drug development.Read moreRead less
Antiviral compounds to inhibit the replicase of hepatitis C virus. Hepatitis C virus is a major public health problem. There are currently 200,000 infected individuals in Australia and 16,000 new infections every year. There is no specific treatment and current therapy treats a small percentage of patients only, which consists of interferon-alpha and ribavirin. This results in side effects and only a 50% cure rate. This study's outcomes are expected to lead to greater access to treatment and imp ....Antiviral compounds to inhibit the replicase of hepatitis C virus. Hepatitis C virus is a major public health problem. There are currently 200,000 infected individuals in Australia and 16,000 new infections every year. There is no specific treatment and current therapy treats a small percentage of patients only, which consists of interferon-alpha and ribavirin. This results in side effects and only a 50% cure rate. This study's outcomes are expected to lead to greater access to treatment and improved therapy resulting in higher cure rates and in a dramatic reduction in the cost of treating patients. A novel therapy will provide considerable benefits for the national biotechnology industry.Read moreRead less
Mosquito-borne viruses - how they cause disease and novel approaches to prevention. In Australia, Ross River virus (RRV) is the most common insect borne virus that affects human health. There were more than 60,000 confirmed cases of RRV between 1993 and 2008. While not fatal, the disease is responsible for significant morbidity that has both social and economic costs for the individual, their family and the community. This project has several national benefits. It will elucidate whether there is ....Mosquito-borne viruses - how they cause disease and novel approaches to prevention. In Australia, Ross River virus (RRV) is the most common insect borne virus that affects human health. There were more than 60,000 confirmed cases of RRV between 1993 and 2008. While not fatal, the disease is responsible for significant morbidity that has both social and economic costs for the individual, their family and the community. This project has several national benefits. It will elucidate whether there is an association between RRV strain and the severity of disease and if there are human factors that affect the seriousness of symptoms. Knowledge of both of these could provide new avenues for the design of prevention and treatment strategies.Read moreRead less
Investigating The Host Determinants Of Viral Clearance Versus Collateral Pathology In Chronic Infection
Funder
National Health and Medical Research Council
Funding Amount
$1,250,756.00
Summary
Hepatitis B virus has infected over 2 billion people. Some people control the virus but it remains incurable and there is a lifelong risk of liver cancer. Understanding how host cells interact with the virus, the mechanisms the cells use in an attempt to eliminate the virus and the mechanisms the virus uses to sabotage these responses, will provide insights that could lead to therapies. Potential therapies could be applicable to other infections like HIV-1 and tuberculosis.
Elucidating The Mechanisms And Consequences Of Clinical HIV-1 Resistance To The CCR5 Antagonist Maraviroc
Funder
National Health and Medical Research Council
Funding Amount
$622,732.00
Summary
CCR5 antagonists are a new class of anti-HIV drug, and maraviroc (MVC) is the only CCR5 antagonists that is licensed for use as a HIV treatment. Like all HIV treatments, drug resistance to MVC can develop in patients. This study will determine the mechanism of how HIV becomes resistant to MVC, which will permit the development of improved, second generation CCR5 antagonists, and will reveal ways to determine which patients are more likely to develop MVC resistance.