The Role Of Noncoding Subgenomic Flavivirus RNA In Virus-host Interactions
Funder
National Health and Medical Research Council
Funding Amount
$624,429.00
Summary
Flaviviruses such as Dengue, Japanese encephalitis , and West Nile are major human pathogens causing more than 50 million infections per year. Elements in viral genome responsible for pathogenesis of these viruses are not well defined. Recently we have identified a unique for these viruses noncoding subgenomic flavivirus RNA (sfRNA) and showed that it is contributing to viral pathogenesis. In this proposal we aim to determine mechanisms by which sfRNA facilitates viral pathogenesis.
Viral And Host Factors Determining Outcome Of Zika Virus Infection
Funder
National Health and Medical Research Council
Funding Amount
$910,780.00
Summary
The proposal aims at identifying viral and host factors determining outcomes of infection with Zika virus, a significant mosquito-transmitted pathogen associated with debilitating neurological pathology in new-borne babies from mothers infected during pregnancy. We will use cutting edge methodologies and infections models to bring our understanding of Zika virus infection to unprecedented level. The results could also facilitate identification of targets for effective anti-viral therapy.
Current combination antiviral therapy can't cure an HIV infection because long-lived T-cells carrying latent HIV DNA can rekindle the infection when drugs are removed. We will study elements in HIV genetic code that control expression of HIV proteins from latent HIV. A detailed molecular understanding of the structure and function of these HIV RNA elements and the viral and host cell factors that interact with them will expose new targets for therapy of latent HIV.
Successful HIV remission and cure, where patients can live normally without daily drug therapy and risk of transmitting infectious virus, will critically depend on understanding the mechanisms that control the expression of viral messenger RNA and proteins. This project further explores the mechanisms controling poorly understood steps in the proecssing of viral mRNA that are required for HIV protein produciton, and identifies new targets and strategies to drive HIV into permanent remission.
Control Of Viral Replication By Non-coding Viral RNA
Funder
National Health and Medical Research Council
Funding Amount
$502,270.00
Summary
In 25 years since identified, HIV-AIDS deaths have exceeded 30 million and 40 million more are now living with HIV. The toll will soon far surpass any other infectious disease epidemic in history, or even military deaths from war in the past century. While effective combination drug therapies are available, multi-drug resistant HIV strains are commonly transmitted, leaving some patients with limited treatment options. New classes of drugs aimed at different steps in virus replication are urgentl ....In 25 years since identified, HIV-AIDS deaths have exceeded 30 million and 40 million more are now living with HIV. The toll will soon far surpass any other infectious disease epidemic in history, or even military deaths from war in the past century. While effective combination drug therapies are available, multi-drug resistant HIV strains are commonly transmitted, leaving some patients with limited treatment options. New classes of drugs aimed at different steps in virus replication are urgently needed. We have discovered that viral RNAs that do not code for protein serve important functions in HIV replication. We will study the molecular mechanisms these non-coding (intron) RNAs previously considered junk use to support of HIV gene expression and assess their potential as drug targets. First, we will investigate the role of these junk RNA loops, or lariat introns, produced in large amounts during the HIV replication cycle. Retroviruses employ RNA splicing to make mRNA for envelope and regulatory accessory genes. The complex alternative RNA splicing pattern of HIV spawns several non-coding lariats, including the lariat-intron that contains much of the removed env coding sequence. We have made the counterintuitive finding that the env-lariat dramatically enhances expression of Env protein. We will examine how this occurs and the involvement of the new class of gene-expression controlling micro-RNAs in this process. We will test for functional activity from the other lariat-introns that are produced by HIV. Second, we will characterise the mRNA-element required for efficient expression of the HIV envelope glycoprotein, Env gp160, which is essential for virus binding and entry during infection. This RNA-element directs the cell protein translation machinery to commence protein synthesis at the start of the Envgp160 rather than at upstream start sites for Vpu and Rev. We will determine how this RNA element works, its structure, and how it might be inactivated.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.
Novel Antivirals For The Treatment Of Hendravirus Infection.
Funder
National Health and Medical Research Council
Funding Amount
$199,227.00
Summary
Hendravirus outbreaks have become frequent and 7 human cases have been reported, this has resulted in 4 deaths. Currently we have no treatment options. Researchers at Griffith University and the CSIRO have developed a new treatment that attacks the virus by turning off the viral genes at the site of infection. The plan is to treat patients soon after infection to slow or stop the virus and allow patients to recover naturally from this highly lethal disease.