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.
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.
Targeting Myeloid Cells To Restrict Gamma-herpesvirus Spread
Funder
National Health and Medical Research Council
Funding Amount
$643,152.00
Summary
Gamma-herpesviruses infect most people and cause cancers. Vaccines to date have worked poorly. We have identified a key role for myeloid cells in infection that suggests a new approach. Interferons restrict infection in some myeloid cells. We will test whether inducing interferons can make all myeloid cells restrictive and reduce chronic infection. We will test then whether myeloid-restricting antibodies can recruit the same defences to provide a basis for vaccination.
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.
Cell Type Specific Biologic Responses To HIV Infection
Funder
National Health and Medical Research Council
Funding Amount
$636,242.00
Summary
The way in which HIV alters the internal environment of its target cells to facilitate its growth will be examined. These changes enhance its ability to gain a toehold in the human body after entering the genital tract and its persistence for life in the brain and elsewhere in the body.
Elucidating Unique Molecular Mechanisms Involved In HIV-1 Subtype C Pathogenicity
Funder
National Health and Medical Research Council
Funding Amount
$710,989.00
Summary
Most people infected with human immunodeficiency virus (HIV) have subtype C virus (C-HIV) and live in Southern Africa and Central Asia. These regions are where the HIV pandemic is at its worst. However, we know very little about C-HIV. We have evidence that C-HIV evolves differently compared to other HIV-1 subtypes, which impacts the way it leads to AIDS. This project aims to characterise these unique molecular mechanisms, which may lead to vaccines and drugs that are optimised for C-HIV.
Elucidating The Flexibility Of Coreceptor Engagement By HIV-1 Important For Macrophage Tropism And Escape From Entry Inhibitors
Funder
National Health and Medical Research Council
Funding Amount
$635,506.00
Summary
CCR5 antagonists are a new type of anti-HIV-1 drug that stops the virus from entering cells. We have evidence to suggest that the ability of CCR5 antagonists to function properly is linked to the ability of HIV-1 to infect a type of immune cell called macrophages. In this proposal, we will investigate precisely how HIV-1 enters macrophage cells, and then determine how this may influence the outcome of patients who are receiving these drugs as part of their clinical care.