Molecular Mechanisms Of Varicella Zoster Virus Interactions With Key Target Cells
Funder
National Health and Medical Research Council
Funding Amount
$421,650.00
Summary
Varicella zoster virus (VZV) is a herpesvirus which infects up to 90% of the population. VZV causes chickenpox (varicella) predominantly in childhood and shingles (herpes zoster) in middle to old age people. Whilst VZV usually causes relatively mild disease in healthy individuals, VZV still causes significant morbidity in children and adults. VZV causes life-threatening disease in immunocompromised individuals such as patients who are elderly or have HIV disease . Herpes zoster affects many eder ....Varicella zoster virus (VZV) is a herpesvirus which infects up to 90% of the population. VZV causes chickenpox (varicella) predominantly in childhood and shingles (herpes zoster) in middle to old age people. Whilst VZV usually causes relatively mild disease in healthy individuals, VZV still causes significant morbidity in children and adults. VZV causes life-threatening disease in immunocompromised individuals such as patients who are elderly or have HIV disease . Herpes zoster affects many ederly individuals and a major complication is prolonged severe pain or post-herpetic neuralgia (PHN), both severely debilitating and which often requires follow-up medical care for months or years after the initial attack. Despite its significant impact on the community, little is known about the molecular details of how this virus functions. This project aims to improve our understanding of how VZV infection affects specialised human cells in order to make further advances in antiviral therapies as well improve vaccine design for the treatment or prevention of VZV disease and the crippling complication of PHN. This project has four components: (1) We will continue studies which have shown that VZV may actively avoid detection by the immune system. We aim to identify the mechanism and viral genes responsible for interfering with the expression of molecules which are essential for our immune system. (2) We will determine whether VZV infection of specialised immune cells (called dendritic cells) will affect their ability to function and interact with other immune cells (called T cells). (3) We will examine how VZV interacts in human nerve cells (neurons) and whether infected neurons undergo specially programmed cell death (apoptosis). (4) We will examine how different human cells change when they are infected with VZV. A new and exciting technology called DNA microarray now makes it possible to examine the expression of many thousands of genes in one experiment.Read moreRead less
Resolving Human Immunodeficiency Virus (HIV) Transmission
Funder
National Health and Medical Research Council
Funding Amount
$745,213.00
Summary
To increase the breadth of HIV prevention strategies, it is imperative that we biologically understand how HIV enters our bodies. Through two unique clinical cohorts, we will determine why circumcision is protective and how a commonly acquired sexual transmitted infection (human papilloma virus) can increase HIV transmission.
A NOVEL MOUSE MODEL TO INVESTIGATE THE MECHANISMS OF VIRUS-INDUCED ARTHRITIS
Funder
National Health and Medical Research Council
Funding Amount
$336,000.00
Summary
We have developed a novel animal model by which to study arthritic disease caused by insect-transmitted viruses known as arboviruses. The existence of this model and novel reagents provides an excellent opportunity to further explore the basic mechanisms of infectious disease in a complete functioning animal, rather than specific cultured cells. The study will use modern approaches in molecular and cellular biology to achieve this goal. The production by our immune systems of soluble mediators ( ....We have developed a novel animal model by which to study arthritic disease caused by insect-transmitted viruses known as arboviruses. The existence of this model and novel reagents provides an excellent opportunity to further explore the basic mechanisms of infectious disease in a complete functioning animal, rather than specific cultured cells. The study will use modern approaches in molecular and cellular biology to achieve this goal. The production by our immune systems of soluble mediators (cytokines-chemokines) and antibodies is an overwhelming positive aspect of our physiological response to infection by microbes. Protection from disease by these immune compounds can happen naturally, or the body's ability to produce these factors can be exploited to our benefit via the administration of vaccines. However, these factors can also be detrimental to the host contributing to severe disease. For instance, work performed almost 40 years ago showed for the first time that under particular conditions, antibodies against viruses can enhance infection, instead of inhibiting infection as normally seen. In the intervening years work by scientists all over the world has associated antibody-dependent enhancement (ADE) of infection to many types of viruses; ADE is even thought to be a risk factor to serious disease with dengue virus, and has been shown in vitro for the AIDS virus and Ebola virus. We have recently discovered a molecular mechanism which explains how antibody enhances viral infection in vitro. In studies on immune cells infected with Ross River Virus (RRV) we found that infection helped by antibody resulted in the specific disruption to the production of cellular chemicals which are toxic to viruses. Are these mechanisms of antibody-enhanced infection also found in animals? Will such mode of infection cause enhanced disease and tissue pathology (arthritis) in animals?Read moreRead less
Arbovirus Activation And Modulation Of NLRP3 Inflammasome
Funder
National Health and Medical Research Council
Funding Amount
$779,720.00
Summary
This project aims to establish how mosquito borne viruses such as Ross River and dengue viruses interacts with the human host to cause disease, including how the virus evades the host’s immune response to persist and cause disease for prolonged periods. Knowing how differences in the virus and the host’s immune system interplay to cause asymptomatic to severely disabling disease will assist in devising new treatments and prevention programs to lessen the impact of these diseases in Australia.
New Insights Into Viral Inflammatory Disease Mechanisms And Approaches To Therapy
Funder
National Health and Medical Research Council
Funding Amount
$631,010.00
Summary
This fellowship aims to establish how viruses cause disease, including how they evade the immune response to persist and cause disease for prolonged periods. My vision is that knowing how the virus and the immune system interact to determine disease severity will assist in devising new treatments and prevention programs to lessen the impact of viral diseases in Australia and worldwide.
Exploring The Role Of Respiratory Virus Infections In Childhood Asthma Exacerbations
Funder
National Health and Medical Research Council
Funding Amount
$596,649.00
Summary
The PEAK study will explore the reasons children get worse asthma symptoms when they get colds. These reasons examined include the asthma medications taken (or not taken), allergies and exposure to allergens and the type of virus involved. The study follows the children over the whole school term and uses a new way to sample virus by collecting it in the breath, this is more comfortable than old methods and can be done at home.
Mosquito-borne alphaviruses such as Ross River and chikungunya viruses cause widespread epidemics and exert extreme pressure on the public health systems of affected regions. Alphaviruses spreads to joints and triggers a severe disease in those affected. There are no effective treatments or vaccines. The project will investigate virus-host interaction at the bite site. The outcome will be new knowledge to treat infection at the mosquito bite site to prevent joint disease.
Novel Insights Into The Pathobiology Of Alphavirus Infections
Funder
National Health and Medical Research Council
Funding Amount
$827,660.00
Summary
Infections with mosquito-borne viruses are increasing at an alarming rate worldwide. Ross River virus is endemic in parts of Australia, PNG and Pacific islands, while chikungunya virus is distributed globally and causes recurrent pandemics that involve millions of people. These viruses cause severe musculoskeletal disease for several months after infection. This project aims to establish how these viruses interact with the human host to cause disease and may provide a basis for new treatments.
Glycotherapeutics; A New Class Of Treatment For Alphavirus-induced Musculoskeletal Disease
Funder
National Health and Medical Research Council
Funding Amount
$449,868.00
Summary
The hallmark of alphavirus disease is crippling pain and joint arthritis, which often has an extended duration. Currently there is no licenced specific treatment for alphavirus disease and the increasing spread of infection highlights an urgent need for therapeutic intervention strategies. This grant looks at the potential of pentosan polysulfate as a promising drug-repurposing candidate for the treatment of alphavirus-induced arthritis.