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.
Argonaute Proteins In The Mammalian Antiviral Response
Funder
National Health and Medical Research Council
Summary
Viruses are the most abundant infectious agents on earth, and the diseases caused by them are a constant threat and cause of mortality worldwide. Awarded the Nobel Prize for Medicine in 2006, RNA interference (RNAi) is a natural process that plants use to attack viruses. Humans possess all of the tools for RNAi, but whether it is used for antiviral defense is unknown. This study aims to uncover this immune process which will open new avenues to treat virus infections, such as influenza and HIV.
Defining The Molecular Effectors And Regulators Of Anti-viral Immune Responses
Funder
National Health and Medical Research Council
Funding Amount
$447,750.00
Summary
In humans, cytomegalovirus infection can cause severe disease and may even be fatal in individuals with immature or compromised immune systems, such as newborns, AIDS patients, transplant recipients and people treated with chemotherapeutic drugs. The majority of healthy individuals however can clear the infection with minimal disease. The ability of cytomegalovirus to cause disease is increased in the absence of effective immune responses which would normally clear the virus before illness occur ....In humans, cytomegalovirus infection can cause severe disease and may even be fatal in individuals with immature or compromised immune systems, such as newborns, AIDS patients, transplant recipients and people treated with chemotherapeutic drugs. The majority of healthy individuals however can clear the infection with minimal disease. The ability of cytomegalovirus to cause disease is increased in the absence of effective immune responses which would normally clear the virus before illness occurs. Understanding the role of specific mediators of anti-viral immune responses is therefore of paramount importance in establishing the guidelines for the design of more effective anti-viral therapies. The mouse model of cytomegalovirus infection provides a unique system to dissect the roles of specific components of the immune response during the course of viral infection. Our previous studies have shown that anti-viral immune responses are complex and involve a multitude of players. The central aim of the work in the current proposal is to establish the precise contribution of specific molecular effectors and regulators of anti-viral immune responses and define their relevance during the different stages of viral infection. Hence, the results of these studies will be relevant to understanding the pathogenesis of cytomegalovirus infection in humans and more importantly will provide critical insights into the rational design of improved antiviral drugs and vaccines. Since the molecules and cells under investigation are also known to play a crucial role in immune responses that control tumour growth and transplant survival, the proposed studies will provide valuable insight towards the development of new therapies for pathologies associated not only with cytomegalovirus infection, but also with the conditions named above.Read moreRead less
Norovirus Infection At The Stress Granule-PKR-p-elF2α Axis
Funder
National Health and Medical Research Council
Funding Amount
$505,967.00
Summary
This project application will aim to investigate and understand how viruses that cause vomiting and diarrhoea are able to infect, proliferate and spread within the human body. It aims to address how viruses are able to avoid and replicate in the presence of an effective immune response. We have evidence showing that Noroviruses are able to exploit certain antiviral proteins to paradoxically aid in virus replication and survival.
Inhibition Of Interferon-alpah-beta By Chikungunya Virus And The Induction Of Arthritis
Funder
National Health and Medical Research Council
Funding Amount
$709,193.00
Summary
Chikungunya virus is a mosquito borne virus which has caused epidemics of arthritis around the world (recently 260,000 people Reunion Island, France and 1.6 million people in India). The virus is ordinarily very sensitive to the main mammalian anti-viral defence system (interferon alpha-beta). This grant seeks to understand how, despite the activation of this system during infection, the virus manages to persist and cause 3-6 months of debilitating arthritis.
Understanding The Host Pathogen Relationships Of Hendra Virus In Bats, Horses And Humans
Funder
National Health and Medical Research Council
Funding Amount
$648,339.00
Summary
We will examine why bats can be infected with Hendra Virus with no apparent symptoms, yet the virus causes severe disease in other mammals including humans. We will examine the innate immune response towards the virus in the natural host (fruit bats), horses and humans. In addition to the innate immune response we will also examine the adaptive immune response in bats and humans. We hope this information can be used to design new drugs or vaccines to Hendra Virus.
Understanding The Innate Immune Response To Viral Infection Of The Female Reproductive Tract And Placenta
Funder
National Health and Medical Research Council
Funding Amount
$784,273.00
Summary
Viral infection of the female reproductive tract (FRT) can have a significant impact on FRT health and may cause significant birth defects if the virus infects the placenta and developing fetus. In this application we will investigate the role of a novel molecule termed interferon epsilon and how it impacts viral infection of the FRT, the fetus and how the placenta responds to viral infection. This work will develop innovative antiviral strategies to combat viral infections of the FRT.
THE IMMUNOLOGICAL LEGACY OF OBESITY ON VIRAL PATHOGENESIS
Funder
National Health and Medical Research Council
Funding Amount
$652,275.00
Summary
Obesity is a key risk factor for severe viral infections. Our preliminary data suggest that in mice this susceptibility is not reduced by weight loss. In this grant we will investigate a) the mechanisms driving the legacy effect of obesity on antiviral immunity b) whether or not we can reverse this legacy effect by treatment with the drug MCC950 and c) the antiviral response of overweight children and adults who have and haven't recently lost weight.
microRNAs (miRNAs) constitute a novel mechanism used by cells and viruses to regulate gene expression. Studies carried out in non-human primates demonstrated great potential for miRNA-inhibiting drugs as novel antiviral agents against hepatitis C virus infection. By characterising how miRNAs control the antiviral state, we will gain new insights into how miRNA-modulating drugs could present novel strategies to treat viral infections.