Current anti-HIV therapies can't cure HIV because HIV remains silent(latent) in long-lived cells. The HIV life cycle and virus production is linked to activation of the host cell, which is regulated by dendritic cells. This grant will explore how the factors controlling T cell activation and proliferation control virus expression and latency. By understanding how latent infection is established and maintained, these studies will potentially identify new ways to eliminate HIV infection.
Herpesviruses infect us all and cause cancer, blindness, and congenital disability. Developing vaccines requires information from both patients and experimental animals. CD4 T cells seem to suppress directly virus replication, and cells in the nose provide an important way for herpesviruses to get in. We will test whether CD4 T cells can clear nasal infection; what targets they recognize; and how they act. Thus we can establish whether CD4 T cell-directed vaccines might protect against disease.
Mechanisms By Which Varicella Zoster Virus And Herpes Simplex Virus Control Host Functions To Enhance Pathogenesis
Funder
National Health and Medical Research Council
Funding Amount
$631,999.00
Summary
Varicella Zoster Virus and Herpes Simplex Virus are alpha-herpesviruses that cause diseases in a majority of the human population. This proposal will explore issues fundamental to disease and pathogenesis of these two closely related herpesviruses, focusing on how these viruses can control host function. In particular, we will define the interactions between these viruses and the natural killer (NK) cell response.
Prophylactic Vaccine Development For The Elimination Of Hepatitis C
Funder
National Health and Medical Research Council
Funding Amount
$936,752.00
Summary
A vaccine that prevents Hepatitis C is urgently needed to prevent infection and assist with global HCV elimination targets. This project grant will advance world-leading HCV vaccine candidates that generate both humoral and cellular immunity for clinical development.
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.
Understanding The Role Of Host Arih2 In Defence Against Viral Infection And Disease Pathogenesis
Funder
National Health and Medical Research Council
Funding Amount
$537,737.00
Summary
A set of proteins, called E3 ligases, modulate many aspects of immunity. Arih 2 is a novel E3 ligase that limits immune cell activation to maintain the immune system in a quiescent state. The details of how Arih2 functions and its role in immunity to chronic overwhelming infection are the focus of this study. The insights gained from these studies have important implications for our understanding of how immune responses can be promoted during infection or halted in autoimmunity.
Rotavirus is the main cause of severe diarrhoea in children worldwide. In this project, we aim to understand the nature of the first-line immune response to rotavirus in the gut, and elucidate how RV counteracts this response to promote infection. These studies will increase our understanding of how rotavirus causes disease, and facilitate the choice of rotavirus targets for drug development and improved vaccines.
Viral Determinants Of HIV-1 Transcriptional Latency In The Central Nervous System
Funder
National Health and Medical Research Council
Funding Amount
$632,489.00
Summary
The anti-HIV drugs that are currently used to treat HIV-1 infection cannot eliminate the virus from the body, and therefore, cannot cure HIV-1 infection. The major reason why the drugs cannot provide a cure is because they cannot reach virus that hides in particular cells types referred to as "reservoirs". This study will determine how HIV-1 can take sanctuary in these reservoirs, which will be critical information for strategies that aim to cure HIV-1 infection.
Viral Determinants Of HIV-1 Transcriptional Latency In The Central Nervous System: Impact On Cure Strategies
Funder
National Health and Medical Research Council
Funding Amount
$847,521.00
Summary
This grant will identify the factors responsible for HIV-1 latency in the CNS, and will determine the effect of drugs aimed at reversing latency both on HIV-1 within the CNS, and also on the cells of the CNS.