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Defining A Novel Mechanism Of Control Of Host Functions By Human Cytomegalovirus That Enhances Viral Pathogenesis
Funder
National Health and Medical Research Council
Funding Amount
$616,518.00
Summary
Human cytomegalovirus (HCMV) remains a significant human pathogen which causes serious and often life-threatening disease in immunosuppressed people such as bone marrow and solid organ transplant patients and in unborn babies infected during pregnancy. This project will define how HCMV controls host defences by actively modifying the cells it infects to create an environment favourable to continued viral infection and disease.
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.
Prophylactic Vaccine To Prevent Cytomegalovirus Disease
Funder
National Health and Medical Research Council
Funding Amount
$436,360.00
Summary
This project is aiming to develop a prophylactic vaccine against a common herpesvirus which has been linked to the birth defects in new born babies and significant morbidity and mortality in transplant patients. In this project we are testing a novel nanoparticle-based vaccine formulation which stimulates the immune system with single injection and the immunity induced is sustained for long-term.
Multiple Cytomegalovirus Infections: Biological And Evolutionary Significance.
Funder
National Health and Medical Research Council
Funding Amount
$555,776.00
Summary
This project involves the study of cytomegalovirus (CMV) a common viral infection of humans which normally cause little disease. However in individuals whose immune system is suppressed (such as AIDS patients or transplant recipients), or in infection of pregnant women, CMV can cause serious or life-threatening disease in the patient or foetus. An interesting feature of CMV diseases in such patients is that enhanced viral growth and more severe disease is frequently associated with the presence ....This project involves the study of cytomegalovirus (CMV) a common viral infection of humans which normally cause little disease. However in individuals whose immune system is suppressed (such as AIDS patients or transplant recipients), or in infection of pregnant women, CMV can cause serious or life-threatening disease in the patient or foetus. An interesting feature of CMV diseases in such patients is that enhanced viral growth and more severe disease is frequently associated with the presence of multiple strains of CMV in the patient. We suggest that mixed CMV infections provide a survival advantage to the virus, with different strains within the mixed infection assisting the growth of other strains. This would result in increased virus growth overall, and enhanced disease. To study the mechanisms by which multiple infections with different CMV strains may affect both the virus and the host, experiments will be performed using an animal model of CMV, murine cytomegalovirus (MCMV). We will examine the effect of the presence of multiple strains of virus on virus growth and distribution within the infected host. We will also determine if functional MCMV strains are capable of assisting non-functional strains to survive within the host. These studies are relevant to the design of a CMV vaccine, and will be valuable in revealing the ways in which viruses can co-operate within an infection.Read moreRead less
The Balance Of Signals Received By NK Cells Is Modulated By Viruses As A Mean Of Immune Escape.
Funder
National Health and Medical Research Council
Funding Amount
$583,175.00
Summary
Cytomegalovirus (CMV) affects about 60% of the population in Australia. Infection is partially controlled by the immune system but CMV is never eliminated and people remain carriers for the rest of their life. Reactivation of CMV in healthy individuals is usually asymptomatic, but it causes severe diseases in people with immune deficiencies. We seek to discover the mechanisms used by CMV to escape immune surveillance, in order to gain insights into the development of improved antiviral therapies
The Pathogenesis And Prevention Of Congenital Cytomegalovirus Disease
Funder
National Health and Medical Research Council
Funding Amount
$318,768.00
Summary
Cytomegalovirus (CMV) infection during pregnancy can have devastating effects on the developing baby, causing life-long disease and fetal death. Despite CMV being the most common infectious cause of fetal injury, there are significant gaps in our understanding of this congenital disease and no therapeutics available for use during pregnancy. This study will investigate the genetic molecular mechanisms by which CMV causes fetal injury and develop interventional therapies to reduce disease.
Human Cytomegalovirus Encoded Control Of The Latent Phase Of Infection
Funder
National Health and Medical Research Council
Funding Amount
$639,871.00
Summary
Human cytomegalovirus has the ability to hide in the body of a person throughout their life time without it making them ill but the virus can awaken (reactivate) from this latent state and produce new virus. In immunosuppressed people such as transplant patients this reactivation causes significant problems, even death, yet this latency remains poorly understood. This project will help us to understand how the virus can hide successfully from the immune system in a latent form in the human host.
Determination Of The Mechanisms Of Action Of A Cytomegalovirus Chemokine Receptor Homologue In Pathogenesis
Funder
National Health and Medical Research Council
Funding Amount
$251,341.00
Summary
A number of herpesviruses encode proteins that are similar to proteins of our immune system. These pirated proteins are exploited by the virus to enable it to replicate and persist in the infected individual, usually by evading or gaining advantage from the normal immune response. This project will investigate the role of one such protein found in both human and animal herpesviruses (specifically cytomegaloviruses (CMV)) that is conserved with cellular cell surface proteins (receptors) that bind ....A number of herpesviruses encode proteins that are similar to proteins of our immune system. These pirated proteins are exploited by the virus to enable it to replicate and persist in the infected individual, usually by evading or gaining advantage from the normal immune response. This project will investigate the role of one such protein found in both human and animal herpesviruses (specifically cytomegaloviruses (CMV)) that is conserved with cellular cell surface proteins (receptors) that bind immune signaling molecules (chemokines). Chemokines are important proteins in the early response to infection. Binding of chemokines to their receptors initiates a cascade of signals within the cell that has profound effects on cellular responses to environmental stimuli. Thus, it is believed that herpesviruses have acquired chemokine receptors to modify or react to the immune response, causing infected cells to behave abnormally either despite or in response to chemokine signals. This project will determine how this CMV specific protein affects the function of cells that CMV infects and how this may promote virus replication, dissemination and persistence in infected hosts. We will also engineer CMVs where the activity of the target protein can be inhibited by administration of prototype antiviral drugs. If inhibition of the activity of the protein is found to reduce virus replication, dissemination or persistence, then this will demonstrate that this type of protein would be a suitable target for the development of novel drugs active against CMV infections. CMV can cause serious (potentially life threatening) disease in newborn children (following infection in the uterus) and immunosuppressed people (eg. organ transplant recipients and people with HIV-AIDS). Our studies will improve our understanding of the contribution of a specific CMV protein to disease, thereby assisting efforts to reduce the impact of CMV infections.Read moreRead less
Viral infections that mothers catch during pregnancy still cause much illness in babies either in the womb, or after birth. One of these infections called CMV causes more babies to be born with malformation in Australia than any other infection, and is second only to cerebral palsy as a cause of serious problems in babies. Our studies are examining CMV in mothers and babies, leading to better diagnostic tests, researching use of existing and new antiviral drugs to reduce infection in these mothe ....Viral infections that mothers catch during pregnancy still cause much illness in babies either in the womb, or after birth. One of these infections called CMV causes more babies to be born with malformation in Australia than any other infection, and is second only to cerebral palsy as a cause of serious problems in babies. Our studies are examining CMV in mothers and babies, leading to better diagnostic tests, researching use of existing and new antiviral drugs to reduce infection in these mothers and babies.Read moreRead less
The Role Of The Interaction Of The CMV M11 Immune Evasion Molecule With CD44 In Viral Pathogenesis
Funder
National Health and Medical Research Council
Funding Amount
$457,500.00
Summary
Herpesviruses can cause infections that persist for the lifetime of the host. They have evolved many mechanisms to elude the host's immune response that would otherwise eliminate them. One memberof the herpesvirus family that is particularly adept at avoiding host immunity is cytomegalovirus. This virus, while not causing symptoms in healthy individuals, is a significant cause of disease and mortality in individuals with suppressed immune systems such as transplant and AIDS patients, and in the ....Herpesviruses can cause infections that persist for the lifetime of the host. They have evolved many mechanisms to elude the host's immune response that would otherwise eliminate them. One memberof the herpesvirus family that is particularly adept at avoiding host immunity is cytomegalovirus. This virus, while not causing symptoms in healthy individuals, is a significant cause of disease and mortality in individuals with suppressed immune systems such as transplant and AIDS patients, and in the fetus which has a poorly developed immune system. In the current project we will explore at a molecular level how a virus-encoded molecule called m11 interferes with the functions of a cellular receptor called CD44 that has a range of cell functions including cell migration, activation and proliferation and signal transduction. The interaction of m11 with CD44 modifies cell migration and is likely to affect cell activation. Defining how m11 mediates its affects will allow us to define strategies to develop potential antiviral therapies. As CD44 is also involed in contributing to a range of diseases where inappropriate inflammation develops it may be that m11, or derivatives of it, could be harnessed to ameliorate these inflammatory diseases.Read moreRead less