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.
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.
Avian Influenza: Molecular Basis Of Potential Resistance To Neuraminidase Inhibitors
Funder
National Health and Medical Research Council
Funding Amount
$87,250.00
Summary
In this project we will visualize an avian flu protein bound to various antiviral drugs that are currently in the clinic (Relenza and Tamiflu) or are in clinical development. In the immediate term, the images derived from the project will be a valuable predictive tool for evaluating the likely effectiveness of antiviral drugs and vaccines in response to emerging viral resistance. In the longer term the images could be used to guide the development of new antivirals and vaccines against avian flu ....In this project we will visualize an avian flu protein bound to various antiviral drugs that are currently in the clinic (Relenza and Tamiflu) or are in clinical development. In the immediate term, the images derived from the project will be a valuable predictive tool for evaluating the likely effectiveness of antiviral drugs and vaccines in response to emerging viral resistance. In the longer term the images could be used to guide the development of new antivirals and vaccines against avian flu. This initiative brings together Industry leaders in the development of influenza antivirals and vaccines, CSL and Biota, with a leading Medical Research Institute.Read moreRead less
Influenza A Virus PB1-F2 Protein: A Putative Virulence Factor And Initiator Of Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$474,718.00
Summary
Influenza virus produces a protein of undefined function called PB1-F2. Infection of mice with virus expressing PB1-F2 from virulent strains causes severe lung inflammation, while PB1-F2 from milder seasonal viruses does not. We will examine how PB1-F2 influences virulence of human influenza in the ferret, which exhibits the same illness as humans. This work will help understand the disease severity of newly evolved influenza viruses of humans and the role of PB1-F2 in mediating this.
The Mechanism Of HSV-1 Transport In Sensory Axons And Its Unique Assembly At The Axon Terminus
Funder
National Health and Medical Research Council
Funding Amount
$670,284.00
Summary
Herpes simplex viruses 1 and 2 cause common diseases such as genital herpes and, occasionally, neonatal deaths and encephalitis and predisposes to HIV infection. New antiviral strategies are required for resistant viruses for control. These aims will be facilitated by understanding how HSV is transported down nerves and across into skin. In this study, we will define how a key viral protein plays a major role in assembly of the virus at the tip of the nerve before it enters skin.
Defining The Molecular Mechanisms Of Lyssavirus Replication And Immune Evasion: The P Protein Axis
Funder
National Health and Medical Research Council
Funding Amount
$900,995.00
Summary
Lyssaviruses such as rabies virus (RABV) and Australian bat lyssavirus cause rabies disease, which has the highest case-fatality rate of known infectious diseases, causing >60,000 human deaths/year. Critical to this is a protein produced by the virus that is important for both viral growth and evasion of the host's immune defences. This project aims to understand the molecular mechanisms underlying these processes, which may lead to new approaches to combat currently incurable viral diseases.
Subcellular Trafficking Of P Proteins Of Human Pathogenic Viruses: Roles In Viral Pathogenicity And Targeting For Therapeutics
Funder
National Health and Medical Research Council
Funding Amount
$578,352.00
Summary
In order to infect humans, pathogenic viruses such as rabies, Nipah, Hendra and Australian bat lyssavirus must be able to evade the immune response. To do this, viruses produce "interferon antagonists" that interfere with specific immune processes by mechanisms that are not fully understood. Our study will characterise the mechanisms used by rabies and other viruses to block immunity, and identify strategies to disable viral immune evasion, rendering these lethal viruses susceptible to destructi ....In order to infect humans, pathogenic viruses such as rabies, Nipah, Hendra and Australian bat lyssavirus must be able to evade the immune response. To do this, viruses produce "interferon antagonists" that interfere with specific immune processes by mechanisms that are not fully understood. Our study will characterise the mechanisms used by rabies and other viruses to block immunity, and identify strategies to disable viral immune evasion, rendering these lethal viruses susceptible to destruction by the human immune system.Read moreRead less
The Role Of Vif In Enhancing HIV Replication And Effecting The Integrity Of The Replication Complexes Of HIV
Funder
National Health and Medical Research Council
Funding Amount
$260,200.00
Summary
HIV-AIDS is still one of the leading causes of infectious human fatality worldwide. The genome of HIV encodes six viral accessory proteins that are necessary for viral replication and infection. One of these genes, viral infectivity factor (vif), is essential for production of infectious virus. Exactly how this viral protein works within the cell is not clear at present. Current literature suggests that Vif acts in some way to enhance reverse transcription, one of the early stages of the viral l ....HIV-AIDS is still one of the leading causes of infectious human fatality worldwide. The genome of HIV encodes six viral accessory proteins that are necessary for viral replication and infection. One of these genes, viral infectivity factor (vif), is essential for production of infectious virus. Exactly how this viral protein works within the cell is not clear at present. Current literature suggests that Vif acts in some way to enhance reverse transcription, one of the early stages of the viral life cycle. We aim to investigate the action of Vif in stabilizing early HIV reverse transcription complexes to understand how it acts to enhance HIV replication and viral infection. The early stages of HIV replication are critical for establishing infection and hence ideal targets for therapeutic intervention. This research will help understand how Vif works in a cell and affects the infectivity of HIV viral particles and may be suggestive of potential targets for development of anti-viral drugs.Read moreRead less