Cell Surface Lectin Receptors For Attachment And Entry Of Influenza Viruses Into Cells Of The Innate Immune System
Funder
National Health and Medical Research Council
Funding Amount
$530,094.00
Summary
Influenza virus is a leading cause of respiratory infection and death worldwide. Infection of humans is initiated when the virus contacts cells lining the respiratory tract. Infection of epithelial cells leads to virus amplification whereas infection of immune cells results in virus destruction. Despite extensive research efforts, it is not clear how the virus infects these cells. This project aims to identify receptors on human cells used by influenza virus to attach to and infect immune cells.
Characterising The Genotypic And Phenotypic Properties Of The HIV-1 Viral Reservoir
Funder
National Health and Medical Research Council
Funding Amount
$316,819.00
Summary
Current drug treatments can not eradicate HIV from the body. This is because HIV can infect and establish a latent or “silent” infection in long-lived cells of the immune system that can re-emerge out of these cells when drug treatment is stopped. This project aims to find out how these cells become infected and what type of HIV is infecting them. The results from this study will help us better understand the latent infection and will help researchers design ways to eradicate HIV.
Envelope Glycoprotein Determinants Of HIV-1 Subtype C Tropism And Pathogenicity
Funder
National Health and Medical Research Council
Funding Amount
$657,745.00
Summary
HIV-1 subtype C is the most common subtype of HIV-w worldwide, yet we know comparatively little about how it causes disease in humans. This study will elucidate how HIV-1 subtype C evolves in patients to become more pathogenic over time.
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.
Understanding HIV Resistance To Entry Inhibitors To Advance The Development Of Novel Antivirals
Funder
National Health and Medical Research Council
Funding Amount
$877,585.00
Summary
We cannot afford to be complacent in the search for improved anti HIV drugs for 2 principal reasons; First, worldwide a staggering 66% of infected individuals who need treatment are still unable to access therapy; and Second, the main reason why most treated patients are now living longer and more healthy lives is because we have never stopped developing newer therapies to provide options for patients. In this study we will develop and test newer drugs that block HIV infection of cells.
Functions Of Viral Chemokine Receptor Homologues Important For Cytomegalovirus Pathogenesis And Latency
Funder
National Health and Medical Research Council
Funding Amount
$461,597.00
Summary
Cytomegalovirus (CMV) causes life-threatening disease in babies, transplant recipients and HIV-AIDS patients. We will focus on a CMV gene that has been 'hijacked' from the host cell and enables the virus to switch on signalling molecules within infected cells. We will determine how these signals enable CMV to infect sites of the body that are critical for virus transmission and contribute to long-term virus persistence. Our results will provide new strategies for drugs against CMV.
Roles Of The Hepatitis C Virus Glycoprotein E2 Variable Regions In Virus Entry, Immunogenicity And Immune Evasion.
Funder
National Health and Medical Research Council
Funding Amount
$682,820.00
Summary
Hepatitis C Virus infects 200 million people world-wide with over 200,000 Australians infected with the disease. This project will examine how the surface proteins of HCV change their shape to evade antibody responses and how this effects the outcome of infection. We will further characterize a vaccine that elicits protective immunity to HCV to identify the optimal formulation for clinical trials.
Determination Of The Mechanisms Of Action Of A Cytomegalovirus Chemokine Receptor Homologue In Pathogenesis
Funder
National Health and Medical Research Council
Funding Amount
$251,341.00
Summary
A number of herpesviruses encode proteins that are similar to proteins of our immune system. These pirated proteins are exploited by the virus to enable it to replicate and persist in the infected individual, usually by evading or gaining advantage from the normal immune response. This project will investigate the role of one such protein found in both human and animal herpesviruses (specifically cytomegaloviruses (CMV)) that is conserved with cellular cell surface proteins (receptors) that bind ....A number of herpesviruses encode proteins that are similar to proteins of our immune system. These pirated proteins are exploited by the virus to enable it to replicate and persist in the infected individual, usually by evading or gaining advantage from the normal immune response. This project will investigate the role of one such protein found in both human and animal herpesviruses (specifically cytomegaloviruses (CMV)) that is conserved with cellular cell surface proteins (receptors) that bind immune signaling molecules (chemokines). Chemokines are important proteins in the early response to infection. Binding of chemokines to their receptors initiates a cascade of signals within the cell that has profound effects on cellular responses to environmental stimuli. Thus, it is believed that herpesviruses have acquired chemokine receptors to modify or react to the immune response, causing infected cells to behave abnormally either despite or in response to chemokine signals. This project will determine how this CMV specific protein affects the function of cells that CMV infects and how this may promote virus replication, dissemination and persistence in infected hosts. We will also engineer CMVs where the activity of the target protein can be inhibited by administration of prototype antiviral drugs. If inhibition of the activity of the protein is found to reduce virus replication, dissemination or persistence, then this will demonstrate that this type of protein would be a suitable target for the development of novel drugs active against CMV infections. CMV can cause serious (potentially life threatening) disease in newborn children (following infection in the uterus) and immunosuppressed people (eg. organ transplant recipients and people with HIV-AIDS). Our studies will improve our understanding of the contribution of a specific CMV protein to disease, thereby assisting efforts to reduce the impact of CMV infections.Read moreRead less
Elucidating Unique Molecular Mechanisms Involved In HIV-1 Subtype C Pathogenicity
Funder
National Health and Medical Research Council
Funding Amount
$710,989.00
Summary
Most people infected with human immunodeficiency virus (HIV) have subtype C virus (C-HIV) and live in Southern Africa and Central Asia. These regions are where the HIV pandemic is at its worst. However, we know very little about C-HIV. We have evidence that C-HIV evolves differently compared to other HIV-1 subtypes, which impacts the way it leads to AIDS. This project aims to characterise these unique molecular mechanisms, which may lead to vaccines and drugs that are optimised for C-HIV.
Elucidating The Flexibility Of Coreceptor Engagement By HIV-1 Important For Macrophage Tropism And Escape From Entry Inhibitors
Funder
National Health and Medical Research Council
Funding Amount
$635,506.00
Summary
CCR5 antagonists are a new type of anti-HIV-1 drug that stops the virus from entering cells. We have evidence to suggest that the ability of CCR5 antagonists to function properly is linked to the ability of HIV-1 to infect a type of immune cell called macrophages. In this proposal, we will investigate precisely how HIV-1 enters macrophage cells, and then determine how this may influence the outcome of patients who are receiving these drugs as part of their clinical care.