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
Functions Of Viral Chemokine Receptor Homologues Important For Cytomegalovirus Pathogenesis And Latency
Funder
National Health and Medical Research Council
Funding Amount
$461,597.00
Summary
Cytomegalovirus (CMV) causes life-threatening disease in babies, transplant recipients and HIV-AIDS patients. We will focus on a CMV gene that has been 'hijacked' from the host cell and enables the virus to switch on signalling molecules within infected cells. We will determine how these signals enable CMV to infect sites of the body that are critical for virus transmission and contribute to long-term virus persistence. Our results will provide new strategies for drugs against CMV.
The Role Of The Inflammasome In Modulating Disease During Influenza Virus Infection
Funder
National Health and Medical Research Council
Funding Amount
$616,979.00
Summary
Highly pathogenic influenza A virus (IAV) infections in humans are associated with high mortality rates. This project will provide global and fundamental insights into our understanding of why IAV often cause fatal disease. It will advance knowledge of the mechanisms by which the host and virus interact and elucidate how the host's immune system responds to the infection and modulates disease, to facilitate the development of improved treatments for severe IAV infections.
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.
NEW INSIGHT INTO GLYCAN REQUIREMENTS FOR ROTAVIRUS-CELL ATTACHMENT AND ENTRY
Funder
National Health and Medical Research Council
Funding Amount
$1,068,758.00
Summary
Rotavirus causes significant infection and loss of life in children, particularly in underdeveloped countries. This project will investigate the role of carbohydrates as contact points for this deadly virus towards the goal of developing novel vaccines and drug therapies.
Understanding The Role Of NS Segments In Evading Influenza A Virus-specific Humoral And T Cell Immunity
Funder
National Health and Medical Research Council
Funding Amount
$213,812.00
Summary
Influenza viruses developed two ways to survive against host immune response: (i) mutating in its genes to escape host immune response, which may cause a new pandemic; (ii) using its NS1 protein to impair host immune response. However, little is known on how these two processes occur and whether NS1 could influence the outcome of escape mutants. By using virological and immunological methods, this study will show how viruses use different NS1 to enhance the viral escape mechanism.
Cell Surface Lectin Receptors For Attachment And Entry Of Influenza Viruses Into Cells Of The Innate Immune System
Funder
National Health and Medical Research Council
Funding Amount
$530,094.00
Summary
Influenza virus is a leading cause of respiratory infection and death worldwide. Infection of humans is initiated when the virus contacts cells lining the respiratory tract. Infection of epithelial cells leads to virus amplification whereas infection of immune cells results in virus destruction. Despite extensive research efforts, it is not clear how the virus infects these cells. This project aims to identify receptors on human cells used by influenza virus to attach to and infect immune cells.
Molecular Pathogenesis Of Emerging West Nile Viruses
Funder
National Health and Medical Research Council
Funding Amount
$594,133.00
Summary
West Nile virus (WNV) is a mosquito-borne virus that causes potentially fatal encephalitis in humans and horses. This project will investigate the recent emergence of pathogenic for horses WNV in Australia and the potential of this new isolate to cause severe disease in humans. We will define the viral and host factors determining the outcome of WNV infection. This project will provide knowledge on the factors involved in the emergence of virulent WNV strains from attenuated isolates.