Retroviral Recombination, RNA Dimers & Multiple Drug Resistant HIV-1
Funder
National Health and Medical Research Council
Funding Amount
$405,017.00
Summary
The emergence of multiple drug resistant strains of HIV-1 has threatened the continue success of current clinical treatment to suppress virus propagation. Retroviruses, such as HIV-1, can reshuffle its two copies of genetic materials during the viral replication process, which leads to the production of offspring viruses that contain a mixture of the parental genetic materials. This process of genetic information reshuffling is believed to be important for the generation of multiple drug resista ....The emergence of multiple drug resistant strains of HIV-1 has threatened the continue success of current clinical treatment to suppress virus propagation. Retroviruses, such as HIV-1, can reshuffle its two copies of genetic materials during the viral replication process, which leads to the production of offspring viruses that contain a mixture of the parental genetic materials. This process of genetic information reshuffling is believed to be important for the generation of multiple drug resistant strains of HIV-1. The objective of this proposal is to define the parameters that regulate the reshuffling of HIV-1 genetic materials and to design novel tools to inhibit the production of multiple drug resistant HIV-1.Read moreRead less
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.
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
Characterising The Genotypic And Phenotypic Properties Of The HIV-1 Viral Reservoir
Funder
National Health and Medical Research Council
Funding Amount
$316,819.00
Summary
Current drug treatments can not eradicate HIV from the body. This is because HIV can infect and establish a latent or “silent” infection in long-lived cells of the immune system that can re-emerge out of these cells when drug treatment is stopped. This project aims to find out how these cells become infected and what type of HIV is infecting them. The results from this study will help us better understand the latent infection and will help researchers design ways to eradicate HIV.
Envelope Glycoprotein Determinants Of HIV-1 Subtype C Tropism And Pathogenicity
Funder
National Health and Medical Research Council
Funding Amount
$657,745.00
Summary
HIV-1 subtype C is the most common subtype of HIV-w worldwide, yet we know comparatively little about how it causes disease in humans. This study will elucidate how HIV-1 subtype C evolves in patients to become more pathogenic over time.
Elucidating The Mechanisms And Consequences Of Clinical HIV-1 Resistance To The CCR5 Antagonist Maraviroc
Funder
National Health and Medical Research Council
Funding Amount
$622,732.00
Summary
CCR5 antagonists are a new class of anti-HIV drug, and maraviroc (MVC) is the only CCR5 antagonists that is licensed for use as a HIV treatment. Like all HIV treatments, drug resistance to MVC can develop in patients. This study will determine the mechanism of how HIV becomes resistant to MVC, which will permit the development of improved, second generation CCR5 antagonists, and will reveal ways to determine which patients are more likely to develop MVC resistance.
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.
Understanding HIV Resistance To Entry Inhibitors To Advance The Development Of Novel Antivirals
Funder
National Health and Medical Research Council
Funding Amount
$877,585.00
Summary
We cannot afford to be complacent in the search for improved anti HIV drugs for 2 principal reasons; First, worldwide a staggering 66% of infected individuals who need treatment are still unable to access therapy; and Second, the main reason why most treated patients are now living longer and more healthy lives is because we have never stopped developing newer therapies to provide options for patients. In this study we will develop and test newer drugs that block HIV infection of cells.