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.
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.
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.
Characterize The Post-entry Events Of HIV Infection
Funder
National Health and Medical Research Council
Funding Amount
$605,190.00
Summary
For HIV to successful infect a target cell, it must properly remove the outer layers of its protective gears (outer viral protein coats) to allow the viral genetic materials to be replicate (duplicate and multiplied) for the generation of their ‘offspring viruses’. This process is known as viral uncoating, and it is arguably one of the least understood areas of HIV. In this proposal, we will use a number of complementary state-of-the-arts research tools to characterize the HIV uncoating process.
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.
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.
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.