Human ?-herpesviruses persist for life, cause cancers and emerge with particular virulence when the immune system is weak. Vaccination against them is therefore an important health priority. We have shown for a related ?-herpesvirus of mice that live vaccines protect. Antibody seems to play a major role. We will test whether safer, recombinant vaccines are also sufficient to elicit protective antibody. Thus we can establish a viable strategy for preventing virus-induced human cancers.
Effective Therapies To Treat Viral Infections And Their Complications In Transplantation
Funder
National Health and Medical Research Council
Funding Amount
$1,100,450.00
Summary
Viral infections are a common life threatening complication in transplant recipients, for which there are limited treatment options. We have developed several pre-clinical models that we are using to determine how the treatment of viral infections that occur after transplantation can be improved.
HIV Phenotypes Important For The Establishment Of Persistent Reservoirs In The Central Nervous System And Which Impact Neurotropism And Neuropathogenesis
Funder
National Health and Medical Research Council
Funding Amount
$762,492.00
Summary
This grant will determine whether or not the CNS is a reservoir for HIV and identify the cellular targets of persistent infection and type of HIV-1 present.
Understanding The Key Attributes Of CD8 T Cell Receptor Transfer As An Antiviral Strategy And Harnessing The Process To Combat Persistent Viral Infections
Funder
National Health and Medical Research Council
Funding Amount
$612,885.00
Summary
We have recently discovered a new process through which the numbers of antiviral immune cells can rapidly expand, without dividing, to combat a virus infection that may otherwise be fatal. This represents a significant advance in our knowledge on how a speedy, virus-specific response can be mounted. We will study how this process can be applied to therapeutic strategies to overcome medically significant persistent viral infections.
Worldwide >360 million people have chronic hepatitis B virus (HBV) infection that imparts a 25% lifetime risk of death due to serious liver disease. Current therapies for chronic HBV reduce levels of virus replication but fail to target the stable, nuclear episome, covalently closed circular DNA (cccDNA). The current study will determine what is required to eliminate cccDNA and how current therapies for chronic HBV infection should be modified to achieve this aim.
Improving Treatment Strategies For Chronic Alphaviral Arthritic Diseases
Funder
National Health and Medical Research Council
Funding Amount
$643,624.00
Summary
Chikungunya virus and Ross River virus cause epidemics of acute and chronic arthritic disease in humans, which is often poorly managed with current treatments. This grant seeks to understand the mechanisms that give rise to disease in order to identify improved treatment strategies. Both the persistence of viral replication in joint tissues and unnecessary inflammatory responses appear to be important factors driving chronic disease.
Targeting Redox Homeostasis To Prevent Mycobacterium Tuberculosis Persistence
Funder
National Health and Medical Research Council
Funding Amount
$396,025.00
Summary
Tuberculosis is now the leading cause of death from infectious disease worldwide. This reflects the ability of its causative agent to persist, leading to failure of antibiotic treatment and development of drug resistance. In this project, we propose to overcome this by inhibiting a unique metabolic pathway that is activated when the pathogen enters its persistent state. We will use a cutting-edge combination of techniques to develop this pathway for next-generation therapies.
Targeting Toxoplasma Gondii Latent Stages Responsible For Chronic Disease
Funder
National Health and Medical Research Council
Funding Amount
$697,107.00
Summary
Many microbial pathogens become resistant to host immune response and drugs by entering a slow-growing, dormant state. These stages are commonly responsible for long term, chronic infections. We will investigate the molecular basis of dormancy in Toxoplasma gondii, which infects one in three people. These studies will identify metabolic pathways that are essential for dormancy with the view of developing new therapies for treating long term, recurrent infections.
Herpesviruses infect most Australians and cause recurrent ulcers, birth defects and cancer. Infection lasts lifelong, and spreads to close contacts without obvious clinical signs. Thus disease is hard to prevent. However we can learn much from related animal infections. We have shown that both mouse and human herpesviruses enter mice via cells in the nose. Thus human infections might follow the same route. We will define what body defences work here and whether vaccines can prevent infection.
Viral infections of the gut are one of the most debilitating infections one can suffer from. Noroviruses are the most common causative agents of viral-associated gastroenteritis but unfortunately little is known regarding their biology and pathogenesis. Our study aims to investigate the replication and pathogenesis of a mouse norovirus to shed light on similar aspects relating to human norovirus infection. We aim to understand how virus infection in cells leads to disease symptoms.