The Role Of Rip3 And Caspase 8 In Necroptosis And Apoptosis During Viral Infection
Funder
National Health and Medical Research Council
Funding Amount
$459,499.00
Summary
Programmed cell death can be beneficial or detrimental depending on circumstances. This delicate balance is most obvious during an infection. The host tries to limit the spread of a pathogen by initiating programmed death in infected cells but excessive death particularly in uninfected cells is catastrophic. It is essential to have a thorough understanding of the interplay between cell death mechanisms so we can overt pathological outcomes and this is the focus of our research.
The Role Of Dendritic Cells In Sexual Transmission Of HIV And Viral Reservoir Formation
Funder
National Health and Medical Research Council
Funding Amount
$654,296.00
Summary
This grant aims to determine the subsets of dendritic cells found in the different tissue of the anogenital tracts and to determine which ones play the key roles in HIV transmission. The relative ability of these cells to transfer the virus to activated T cells leading to productive infection and resting memory T cells leading to latent infection will be investigated. Finally the key receptors which mediate this process will be determined and strategies to block this transfer developed.
Understanding The Role Of Host Arih2 In Defence Against Viral Infection And Disease Pathogenesis
Funder
National Health and Medical Research Council
Funding Amount
$537,737.00
Summary
A set of proteins, called E3 ligases, modulate many aspects of immunity. Arih 2 is a novel E3 ligase that limits immune cell activation to maintain the immune system in a quiescent state. The details of how Arih2 functions and its role in immunity to chronic overwhelming infection are the focus of this study. The insights gained from these studies have important implications for our understanding of how immune responses can be promoted during infection or halted in autoimmunity.
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.
The Impact Of HIV Integration Sites On Eliminating HIV Latency
Funder
National Health and Medical Research Council
Funding Amount
$778,313.00
Summary
Current antiviral therapy for HIV controls virus production and allows recovery but does not eliminate the silent infection that prevents complete virus elimination and cure. We will examine two ways that HIV can silently infect T cells for differences in the sites at which the HIV DNA inserts into the genome. We will examine the way in which these differences at the genomic level may limit the ability to activate and eliminate persistent infection in memory T cells.
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.
We will construct different genetically engineered viruses, which infect cells in the respiratory tract, to deliver genes encoding proteins from human immunodeficiency virus (the AIDS virus). These engineered viruses can be expected to generate an active immune response in mucosal tissues, including the vaginal and rectal tracts. As these are the major routes for transmission of the AIDS virus, these new vaccines are expected to reduce transmission of the AIDS virus.
Chronic Active Viral Persistence Versus Host Immune Mediated Pathology: An Analysis And Manipulation Of The Balance.
Funder
National Health and Medical Research Council
Funding Amount
$418,658.00
Summary
Our robust ability to mount an immune response and clear infections is tempered by the possibility of promoting autoimmunity. Several host genes regulate immunity. Viruses like HIV have exploited these to abrogate antiviral immunity. This project attempts to define host factors that promote chronic infection. This will be extremely valuable in understanding the vulnerabilities of our immune system and provide an insight into how we can treat chronic infections.
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.
Enhanced Expression Of The Epstein-Barr Virus Nuclear Antigen, EBNA1, As A Target For T-cell-Based Immunotherapy For Prevention Of Viral-Associated Diseases.
Funder
National Health and Medical Research Council
Funding Amount
$356,513.00
Summary
Epstein-Barr virus, (EBV) is a human herpesvirus associated with a range of human cancers. EBNA1, an important EBV antigen, was thought to be “immunologically silent” however, recent studies from our laboratory show that EBNA1 is recognized by our body's defence system and these observations raise the possibility that EBNA1 may be an exploitable, immuno-therapy target for treating EBV-associated cancers.