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
The Role Of Noncoding Viral RNAs In Flavivirus Infection And Exosomal Signalling
Funder
National Health and Medical Research Council
Funding Amount
$683,447.00
Summary
The application is aimed at investigating the novel role for viral noncoding RNAs in exosomal antiviral signalling and associated outcome of infection with West Nile virus. We will identify host enzymes involved in generation of viral noncoding RNAs, determine which host proteins they interact with and how these interactions determine their incorporation into secreted exosomes to influence outcome of infection.
Understanding How Cytomegaloviruses Establish Systemic Infection
Funder
National Health and Medical Research Council
Funding Amount
$668,144.00
Summary
Human cytomegalovirus (HCMV) infects most Australians, causes birth defects and harms transplant patients. Vaccines against it have worked poorly. HCMV spreads throughout the body and is never cleared. To control infection we must identify its key checkpoints. Using mouse CMV, we find that host dendritic cells, which normally defend against infections, are taken over and spread virus to new sites. The viral gene responsible is a potential target for intervention. We will define how it works.
New Drug Combinations To Enhance Elimination Of Hepatitis B Infection
Funder
National Health and Medical Research Council
Funding Amount
$888,304.00
Summary
We have developed a therapy that kills hepatitis B virus infected cells and promotes elimination of infection. We are now testing novel drugs that can be used to maximise the efficacy of our new treatment to promote better outcomes that may be translated to other infections.
Burden Of Respiratory Infection In The First 2 Years Of Life: A Birth Cohort Study Of Emerging Respiratory Pathogens.
Funder
National Health and Medical Research Council
Funding Amount
$1,168,963.00
Summary
Respiratory illnesses are extremely common, but there is little information about patterns of infection in the community using modern diagnostic tests. Children have the highest rates of infection and transmit to all other age groups. We intend to recruit 138 newborns to monitor respiratory symptoms and collect specimens for testing in the first two years of life. This will allow us to document illnesses due to known and newly identified respiratory pathogens.
Characterization Of Neutralizing Antibody Responses In HCV Infected Individuals.
Funder
National Health and Medical Research Council
Funding Amount
$478,076.00
Summary
Hepatitis C virus is a major human pathogen infecting 200 million people world-wide. Currently, there is no vaccine to prevent infection and treatment regimes are only partially effective. IInitial HCV infection is frequently asymptomatic and 30% of people spontaneously clear the virus. The remaining 70% of people develop a life-long chronic infection that causes progressive liver disease, cirrhosis and in some cases liver cancer. The reason why some people are able to clear virus has been attri ....Hepatitis C virus is a major human pathogen infecting 200 million people world-wide. Currently, there is no vaccine to prevent infection and treatment regimes are only partially effective. IInitial HCV infection is frequently asymptomatic and 30% of people spontaneously clear the virus. The remaining 70% of people develop a life-long chronic infection that causes progressive liver disease, cirrhosis and in some cases liver cancer. The reason why some people are able to clear virus has been attributed to the development of a strong cellular immune response and antibody is belived to play a monir role in achieving viral clearance. However, measurememnt of antibody responses in HCV infected pateints is routinely performed using conventional diagnostic tests that do not measure antibody that can help neutralize and clear virus. We have developed an assay that accurately measures the level of NAb in patient sera. We have found that chronically infected patients have broadly reactive neutralizing antibodies but that patients who clear virus, naturally or through treatment do not have broadly reactive neutralizing antibodies. Possibly explaining this phenomenon is that early during infection, antibody is frequently specific only to the infecting virus therefore to detect neutralizing antibodies, homologous viral sequences must be examined. In addition, we have found evidence that HCV can evade neutralzing antibodies through masking of sites to which antibodies bind. We propose to explore whether acutely infected patients develop NAb to autologous viral sequences, and how do these viral sequences and the antibody titre change throughout the course of infection and treatment. We also plan to determine the mechanism of neutralization resistance through the use of mutagenesis of resistant HCV glycoproteins. These studies are aimed at gaining a thorough understanding of the true role of antibody in HCV infection and its influence on viral evolution.Read moreRead less
Clearing Chronic Infectious Diseases – Enhancing Host Immune Effector Function
Funder
National Health and Medical Research Council
Funding Amount
$92,314.00
Summary
Chronic infections produced by pathogens such as HIV, overwhelm our immune system leading to an exhausted state where cells responsible for the clearance of invading microorganisms are unable to respond effectively. We have recently identified a highly promising therapeutic target that enhances immune effector function. We seek to understand the underlying mechanism, and to explore the therapeutic potential of this approach for the treatment of a broad range of pathogens, including those respons ....Chronic infections produced by pathogens such as HIV, overwhelm our immune system leading to an exhausted state where cells responsible for the clearance of invading microorganisms are unable to respond effectively. We have recently identified a highly promising therapeutic target that enhances immune effector function. We seek to understand the underlying mechanism, and to explore the therapeutic potential of this approach for the treatment of a broad range of pathogens, including those responsible for chronic disease.Read moreRead less
The Role Of Rip3 And Caspase 8 In Necroptosis And Apoptosis During Viral Infection
Funder
National Health and Medical Research Council
Funding Amount
$459,499.00
Summary
Programmed cell death can be beneficial or detrimental depending on circumstances. This delicate balance is most obvious during an infection. The host tries to limit the spread of a pathogen by initiating programmed death in infected cells but excessive death particularly in uninfected cells is catastrophic. It is essential to have a thorough understanding of the interplay between cell death mechanisms so we can overt pathological outcomes and this is the focus of our research.