A Longitudinal Study Of Natural Killer Cell Function In HIV-infected Individuals Initiating Therapy
Funder
National Health and Medical Research Council
Funding Amount
$620,176.00
Summary
HIV infected people no longer die from AIDS but suffer and die from non-AIDS conditions such as non-AIDS related cancers. We have discovered persistent abnormalities in natural killer cells in HIV patients receiving antiretroviral therapy. These cells help prevent the development of and control cancers so understanding why they are abnormal in HIV patients will help prevent early death from non-AIDS cancers.
How The Immune Response Can Affect Influenza Virus And Asthma
Funder
National Health and Medical Research Council
Funding Amount
$333,964.00
Summary
A strong immune response is essential for protection against viral infections. However, in some circumstances a strong immune response against viruses can actually further aggravate disease. In addition, an anti-viral immune response can trigger asthma attacks in allergic individuals. This research thus seeks to understand and therefore mitigate the potentially detrimental role of inflammation in influenza virus infections and asthma.
Respiratory Syncytial Virus Matrix Protein-Host Protein Interactions As Targets For Therapeutics
Funder
National Health and Medical Research Council
Funding Amount
$686,885.00
Summary
Respiratory syncytial virus (RSV) causes more deaths in winter than influenza, being the major cause of viral pneumonia in infants worldwide, and a potent lower respiratory pathogen in the elderly and immunosuppressed adults. The present proposal will apply a range of techniques to search for new inhibitors of viral infection which target host-virus interactions, as the first step towards new generation anti-viral agents to treat RSV infection.
Even in well-resourced countries, the ability to continue treating HIV patients for their lifetime may become unaffordable, which has focused attention on developing a cure for HIV. We have exploited unique insights into a pathway for Tat expression from latent HIV to identify novel compounds that target HIV latency. This project assembles a multidisciplinary team to optimize the lead compounds, and develop novel drug regimens to fast-track into clinical development as a HIV-curative therapy.
Novel Insights Into The Mechanisms Of How Chikungunya Virus Cause Disease In Humans
Funder
National Health and Medical Research Council
Funding Amount
$554,808.00
Summary
Many of the most dangerous and easily transmitted infectious agents are viruses. The emergence of chikungunya virus globally and the recognition of this pathogen in the aetiology of chronic diseases show the need for a better understanding of how the virus cause disease. The expected outcomes are a better understanding of human alphaviral diseases, with a view to improving prevention and treatment strategies to reduce the disease burden of CHIKV and related viruses.
Understanding And Modulating Hyperinflammation Caused By Influenza Viruses
Funder
National Health and Medical Research Council
Funding Amount
$425,048.00
Summary
In humans, highly pathogenic influenza A virus (IAV) infections can be fatal, as the disease is untreatable with available vaccine or anti-viral drugs. My fellowship aims to advance our knowledge of the mechanisms by which the immune system induces and regulates inflammation during IAV infection, which can be both helpful and detrimental in fighting the infection. This is critical for identifying and developing new therapies for severe IAV infections in the future.
The Role Of The Inflammasome In Modulating Disease During Influenza Virus Infection
Funder
National Health and Medical Research Council
Funding Amount
$616,979.00
Summary
Highly pathogenic influenza A virus (IAV) infections in humans are associated with high mortality rates. This project will provide global and fundamental insights into our understanding of why IAV often cause fatal disease. It will advance knowledge of the mechanisms by which the host and virus interact and elucidate how the host's immune system responds to the infection and modulates disease, to facilitate the development of improved treatments for severe IAV infections.
A New Monocyte Atherogenic Phenotype In Chronic HIV Disease.
Funder
National Health and Medical Research Council
Funding Amount
$632,037.00
Summary
Most HIV+ people in Australia now die from cardiovascular disease, caused by atherosclerosis or thickening of coronary arteries. The ability of a white blood cell called the monocyte to prevent atherosclerosis is impaired in HIV. This project aims to understand how HIV does this and how we can reverse the effect. Understanding these processes will also help improve treatments to reduce heart disease in people with other chronic inflammatory conditions.
Control Of Viral Replication By Non-coding Viral RNA
Funder
National Health and Medical Research Council
Funding Amount
$502,270.00
Summary
In 25 years since identified, HIV-AIDS deaths have exceeded 30 million and 40 million more are now living with HIV. The toll will soon far surpass any other infectious disease epidemic in history, or even military deaths from war in the past century. While effective combination drug therapies are available, multi-drug resistant HIV strains are commonly transmitted, leaving some patients with limited treatment options. New classes of drugs aimed at different steps in virus replication are urgentl ....In 25 years since identified, HIV-AIDS deaths have exceeded 30 million and 40 million more are now living with HIV. The toll will soon far surpass any other infectious disease epidemic in history, or even military deaths from war in the past century. While effective combination drug therapies are available, multi-drug resistant HIV strains are commonly transmitted, leaving some patients with limited treatment options. New classes of drugs aimed at different steps in virus replication are urgently needed. We have discovered that viral RNAs that do not code for protein serve important functions in HIV replication. We will study the molecular mechanisms these non-coding (intron) RNAs previously considered junk use to support of HIV gene expression and assess their potential as drug targets. First, we will investigate the role of these junk RNA loops, or lariat introns, produced in large amounts during the HIV replication cycle. Retroviruses employ RNA splicing to make mRNA for envelope and regulatory accessory genes. The complex alternative RNA splicing pattern of HIV spawns several non-coding lariats, including the lariat-intron that contains much of the removed env coding sequence. We have made the counterintuitive finding that the env-lariat dramatically enhances expression of Env protein. We will examine how this occurs and the involvement of the new class of gene-expression controlling micro-RNAs in this process. We will test for functional activity from the other lariat-introns that are produced by HIV. Second, we will characterise the mRNA-element required for efficient expression of the HIV envelope glycoprotein, Env gp160, which is essential for virus binding and entry during infection. This RNA-element directs the cell protein translation machinery to commence protein synthesis at the start of the Envgp160 rather than at upstream start sites for Vpu and Rev. We will determine how this RNA element works, its structure, and how it might be inactivated.Read moreRead less