Understanding How Cytomegaloviruses Establish Systemic Infection
Funder
National Health and Medical Research Council
Funding Amount
$668,144.00
Summary
Human cytomegalovirus (HCMV) infects most Australians, causes birth defects and harms transplant patients. Vaccines against it have worked poorly. HCMV spreads throughout the body and is never cleared. To control infection we must identify its key checkpoints. Using mouse CMV, we find that host dendritic cells, which normally defend against infections, are taken over and spread virus to new sites. The viral gene responsible is a potential target for intervention. We will define how it works.
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.
Targeting Myeloid Cells To Restrict Gamma-herpesvirus Spread
Funder
National Health and Medical Research Council
Funding Amount
$643,152.00
Summary
Gamma-herpesviruses infect most people and cause cancers. Vaccines to date have worked poorly. We have identified a key role for myeloid cells in infection that suggests a new approach. Interferons restrict infection in some myeloid cells. We will test whether inducing interferons can make all myeloid cells restrictive and reduce chronic infection. We will test then whether myeloid-restricting antibodies can recruit the same defences to provide a basis for vaccination.
Current anti-HIV therapies can't cure HIV because HIV remains silent(latent) in long-lived cells. The HIV life cycle and virus production is linked to activation of the host cell, which is regulated by dendritic cells. This grant will explore how the factors controlling T cell activation and proliferation control virus expression and latency. By understanding how latent infection is established and maintained, these studies will potentially identify new ways to eliminate HIV infection.
HIV-1 Transcriptional Gene Silencing By Promoter Targeted Si/shRNAs: Uncovering Mechanisms, Optimising Delivery Systems, Assessing In Vivo Efficacy.
Funder
National Health and Medical Research Council
Funding Amount
$641,789.00
Summary
Current therapy for HIV is effective but must be taken for life. If therapy is stopped the virus comes back immediately from reservoirs not affected by current drugs. These fluctuating levels of virus are associated with increased illness and death. We are exploring a method of inducing prolonged viral latency using short double stranded RNA molecules. We propose to understand the mechanism of action of these possible therapeutics and to develop these constructs towards use in clinical trials.
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.
Roles And Regulation Of Sphingosine Kinase 1 During Dengue Virus Infection
Funder
National Health and Medical Research Council
Funding Amount
$482,795.00
Summary
Dengue virus (DENV) infection is a global human disease with an estimated 50 million infections annually and there is no vaccine or therapy. DENV disease is worsended by the way the body responds to infection and we have investigated these responses. We know the virus changes a molecule in the body called sphingosine-kinase 1 (SK1), which normally controls if cell live or die and how they function. This study will characterise how DENV influences SK1 and if we can target this interaction to deve ....Dengue virus (DENV) infection is a global human disease with an estimated 50 million infections annually and there is no vaccine or therapy. DENV disease is worsended by the way the body responds to infection and we have investigated these responses. We know the virus changes a molecule in the body called sphingosine-kinase 1 (SK1), which normally controls if cell live or die and how they function. This study will characterise how DENV influences SK1 and if we can target this interaction to develop new drugs against DENV infection.Read moreRead less
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.
The Dengue Virus Glycoprotein NS1 Binds Cholesterol And Mediates Cellular Activation
Funder
National Health and Medical Research Council
Funding Amount
$632,029.00
Summary
Cholesterol has been shown to play a vital role in the life cycle of many viruses. This project will investigate the basis of dengue virus interaction with this important host molecule and along with investigations of how dengue is able to stimulate host cells, will provide new insights into the way these viruses cause severe disease. Findings from this study will also aid in the development of new drug strategies for dengue and related viruses such as West Nile virus.
This proposal investigates processes that regulate the cell cytoskeleton to control shape and the dynamics membranes, with a view to developing a generic antiviral therapy. As viruses rely upon the cell cytoskeleton to initiate an infection, we posit that enzymes that control the cytoskeleton can be targeted to block infection.