The Impact Of HIV Integration Sites On Eliminating HIV Latency
Funder
National Health and Medical Research Council
Funding Amount
$778,313.00
Summary
Current antiviral therapy for HIV controls virus production and allows recovery but does not eliminate the silent infection that prevents complete virus elimination and cure. We will examine two ways that HIV can silently infect T cells for differences in the sites at which the HIV DNA inserts into the genome. We will examine the way in which these differences at the genomic level may limit the ability to activate and eliminate persistent infection in memory T cells.
The Role Of Dendritic Cells In Sexual Transmission Of HIV And Viral Reservoir Formation
Funder
National Health and Medical Research Council
Funding Amount
$654,296.00
Summary
This grant aims to determine the subsets of dendritic cells found in the different tissue of the anogenital tracts and to determine which ones play the key roles in HIV transmission. The relative ability of these cells to transfer the virus to activated T cells leading to productive infection and resting memory T cells leading to latent infection will be investigated. Finally the key receptors which mediate this process will be determined and strategies to block this transfer developed.
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.
Defining The Mechanism Of Assembly Of Herpes Simplex Virus In The Neuronal Growth Cone And Its Subsequent Exit To Epithelial Cells
Funder
National Health and Medical Research Council
Funding Amount
$774,624.00
Summary
Herpes simplex virus (HSV) causes dormant infection of nerve cell bodies near the spine. It periodically reactivates to be transported along nerves to the skin where it causes oral, genital or neonatal herpes and mediates HIV superinfection. HSV assembles into its final form in the terminal part of the axon just prior to crossing into skin. Elucidating the mechanism of HSV assembly and exit will facilitate new strategies for antiviral agents and immune treatment for HSV and similar viruses.
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.
Immune Modulatory Effects Of Vaginal Microbiota Metabolites And HIV Susceptibility
Funder
National Health and Medical Research Council
Funding Amount
$795,110.00
Summary
This study will advance knowledge on how acid molecules produced by beneficial and harmful bacteria are able to promote or impede HIV infection of the female genital mucosa through their effects on the barrier and immune function of cells that line the vagina and cervix. The results of this study are anticipated to augment the efficacy of topical HIV prevention strategies and lead to the development of safe vaginal hygiene products that help protect against other sexually transmitted infections.
Chronic Active Viral Persistence Versus Host Immune Mediated Pathology: An Analysis And Manipulation Of The Balance.
Funder
National Health and Medical Research Council
Funding Amount
$418,658.00
Summary
Our robust ability to mount an immune response and clear infections is tempered by the possibility of promoting autoimmunity. Several host genes regulate immunity. Viruses like HIV have exploited these to abrogate antiviral immunity. This project attempts to define host factors that promote chronic infection. This will be extremely valuable in understanding the vulnerabilities of our immune system and provide an insight into how we can treat chronic infections.
A Longitudinal Study Of Natural Killer Cell Function In HIV-infected Individuals Initiating Therapy
Funder
National Health and Medical Research Council
Funding Amount
$620,176.00
Summary
HIV infected people no longer die from AIDS but suffer and die from non-AIDS conditions such as non-AIDS related cancers. We have discovered persistent abnormalities in natural killer cells in HIV patients receiving antiretroviral therapy. These cells help prevent the development of and control cancers so understanding why they are abnormal in HIV patients will help prevent early death from non-AIDS cancers.