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
Bronchiectasis And Infection With The Human T-lymphotropic Virus 1 Among Indigenous Australians
Funder
National Health and Medical Research Council
Funding Amount
$849,674.00
Summary
The Indigenous people of Central Australia have the highest reported prevalence of bronchiectasis in the world. In a recent study, we found infection with Human T -cell Lymphotropic Virus type 1 (HTLV-1) may contribute to the devlopment of bronchiectasis. The present study seeks to confirm this association and to determine whether increased HTLV-1 activity is associated with greater risk. This will require the development of assays that will improve diagnosis and assist in determining prognosis ....The Indigenous people of Central Australia have the highest reported prevalence of bronchiectasis in the world. In a recent study, we found infection with Human T -cell Lymphotropic Virus type 1 (HTLV-1) may contribute to the devlopment of bronchiectasis. The present study seeks to confirm this association and to determine whether increased HTLV-1 activity is associated with greater risk. This will require the development of assays that will improve diagnosis and assist in determining prognosis of HTLV infection.Read moreRead less
Interaction Of Anti-viral IDO And NOS2 In Vivo In A Novel Murine STD Model.
Funder
National Health and Medical Research Council
Funding Amount
$573,629.00
Summary
Sexually transmitted viral diseases (STD) are increasing globally, but we know little of how virus is controlled early in infection. We have shown for the first time in vivo, in our STD model, that during an antiviral immune response, soluble factors turn on an enzyme, indoleamine 2,3-dioxygenase (IDO), to break down and deplete the amino acid, L-tryptophan, starving virus to reduce growth early in STDs. Our project will further define the action and control of IDO in STD.
The Impact Of Influenza A Virus PB1-F2 Protein On Host Immunity And The Potential For Therapeutic Targeting
Funder
National Health and Medical Research Council
Funding Amount
$317,076.00
Summary
The 1918 influenza virus pandemic resulted in 50 million deaths globally and there is potential for new pandemics, such as the predicted H5N1 Bird Flu . Exact causes of such devastating lethality are not fully identified. Newly discovered influenza A virus (IAV) PB1-F2 protein is present in nearly all highly pathogenic IAVs and promotes virus virulence. This study will further examine the way in which PB1-F2 impacts the host, revealing potential therapeutic targets to lessen disease burden.
I am an infectious diseases physician and basic scientist interested in the immunopathogenesis of HIV and hepatitis B virus. My work focuses on HIV viral reservoirs and immune reconstitution and the adaptive immune response to hepatitis B virus.
Genomic Analysis Of Host Response To Influenza A Infection
Funder
National Health and Medical Research Council
Funding Amount
$168,530.00
Summary
Influenza virus infects millions of people globally. However, it remains poorly understood why some infected individuals succumb to life threatening complications whilst others recovered relatively unaffected. This study use advance molecular technique to study influenza infection. It aims to identify the key steps in our immune systems that are progressively disrupted during influenza infection and how this process lead to a break down in our natural defence against the virus.
Modulation Of Leishmaniasis By The Proinflammatory Cytokines TNF
Funder
National Health and Medical Research Council
Funding Amount
$288,911.00
Summary
We have established a mouse model that has been genetically modified and cannot produce the cytokine tumour necrosis factor. This cytokine is secreted in the beginning of the inflammatory response. If these mice are infected with a parasite they are not able to heal the infection and die quickly. We can demonstrate that these mice cannot regulate the beginning inflammatory response and do not form a cellular infiltrate at the site of infection.
Study Of Papillomavirus DNA Encapsidation And Formation Of Infectious Virions
Funder
National Health and Medical Research Council
Funding Amount
$214,053.00
Summary
Papillomavirus (PV) is a sexually-transmitted virus that is a major cause of cervical cancer. Our study will determine how PV is able to form new virus particles inside infected cells. This is a critical part of the virus life-cycle, and a better understanding of this process may allow it to be trageted by anti-viral treatments. In addition, we will develop a method to create non-harmful virus particles which we will use to study human immune responses to the virus.