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.
Dengue Virus NS1 Protein As A Mediator Of Pathology
Funder
National Health and Medical Research Council
Funding Amount
$621,979.00
Summary
Dengue virus is an increasing problem in the tropical world, with estimated infection of more than 300 million people annually. Severe dengue disease can cause life-threatening bleeding and shock. Our project investigates the basis for the pathology of the disease. We have found that a viral protein termed NS1 binds to a receptor on immune cells and leads to production of inflammatory proteins which can promote vessel leakage. We will investigate drugs blocking this, in a disease model.
Mucosal Human Immunodeficiency Virus Vaccine Late Pre-clinical Evaluation
Funder
National Health and Medical Research Council
Funding Amount
$575,315.00
Summary
Despite many candidate vaccines entering clinical development for protection against HIV, none has yet been successful. This proposal centres on late preclinical development for a novel mucosal vaccine strategy for HIV, which combines a preclinically-proven approach to generating strong T cell immune responses, with an existing approach to generating broadly neutralising antibody responses to HIV. Proof of synergy between these approaches will lead directly to clinical development.
Pre-clinica Evaluation Of A Novel HIV-1 Vaccine Statrgy
Funder
National Health and Medical Research Council
Funding Amount
$528,440.00
Summary
Recently, we have designed two mucosal HIV vaccine strategies that temporary block hormone-like molecules IL-4/IL-13 at the vaccination site inducing excellent antibody and killer T cell immunity with protective efficacy in small animals. This project aims to evaluate the safety and efficacy of these novel HIV mucosal vaccines prior to clinical evaluation.
Viruses are considered neither live nor dead, and it is understood that biological process within a virus must occur after it infects a cell. Our work reveals a previous unknown step in HIV known as pre-entry priming. These discoveries challenge our current dogma of how viruses function, and imply this pre-entry priming process is a built in mechanism for HIV to protect itself. This proposal will redefine our understanding of HIV and explore novel HIV vaccine design through these discoveries.
Defining A Virally-encoded Molecular Switch Between Productive And Latent Phases Of Human Cytomegalovirus Infection.
Funder
National Health and Medical Research Council
Funding Amount
$337,614.00
Summary
Human cytomegalovirus (HCMV) is a significant human pathogen which causes serious disease in immunosuppressed people such as bone marrow and solid organ transplant patients. HCMV has the capacity to switch between an active and a dormant state, enabling this virus to remain within the human host, where it can emerge years later to cause disease in immunosuppressed people. This project will define how HCMV controls the switch between active and dormant phases of infection.
Host Cell Signalling During HTLV-1 Infection: Novel Insights And Interventions
Funder
National Health and Medical Research Council
Funding Amount
$62,335.00
Summary
Human T-leukemia virus 1 (HTLV-1) establishes a life-long infection and causes cancer and immune dysfunction. This study aims to find a cure for HTLV-1 by inducing the specific death of infected cells using novel therapeutic drugs that target host cell death pathways. Dead infected cells are then naturally cleared from the system along with the viral infection. The impact of HTLV-1 infection on tuberculosis severity will also be examined.
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
Immune Modulatory Effects Of Vaginal Microbiota Metabolites And HIV Susceptibility
Funder
National Health and Medical Research Council
Funding Amount
$795,110.00
Summary
This study will advance knowledge on how acid molecules produced by beneficial and harmful bacteria are able to promote or impede HIV infection of the female genital mucosa through their effects on the barrier and immune function of cells that line the vagina and cervix. The results of this study are anticipated to augment the efficacy of topical HIV prevention strategies and lead to the development of safe vaginal hygiene products that help protect against other sexually transmitted infections.
The Role Of Actin-based Motility As A Virulence Mechanism And Potential As An Antiviral Target
Funder
National Health and Medical Research Council
Funding Amount
$325,798.00
Summary
Our repertoire of effective treatments for infectious diseases is fast becoming exhausted as resistance to antibiotics and antivirals evolves and rapidly spreads throughout our community. We have developed a new paradigm in treating viral diseases that we predict will not give rise to resistance, and this project will be the first to demonstrate the effectiveness of this novel therapy in an endemic disease model.