SERPINB2 IS AN INDUCIBLE HOST FACTOR INVOLVED IN ENHANCING HIV-1 TRANSCRIPTION AND REPLICATION
Funder
National Health and Medical Research Council
Funding Amount
$496,446.00
Summary
SerpinB2 is one of the most abundant proteins made at sites of inflammation. We have shown that HIV-1 infection also induces SerpinB2 and that SerpinB2 then helps the virus to replicate. In this grant we seek to understand how the virus causes this protein to be made and how this protein then increases virus replication. In the human population there are different forms of SerpinB2 and this grant seeks to determine whether these different forms affect HIV-1 replications differently. It may for i ....SerpinB2 is one of the most abundant proteins made at sites of inflammation. We have shown that HIV-1 infection also induces SerpinB2 and that SerpinB2 then helps the virus to replicate. In this grant we seek to understand how the virus causes this protein to be made and how this protein then increases virus replication. In the human population there are different forms of SerpinB2 and this grant seeks to determine whether these different forms affect HIV-1 replications differently. It may for instance be possible that an individual who has a certain form of SerpinB2 may be less susceptable to AIDS following HIV-1 infection.Read moreRead less
Consequences Of Disulfide Exchange In CD4 For Function
Funder
National Health and Medical Research Council
Funding Amount
$332,580.00
Summary
CD4 is a particular type of receptor on the surface of immune cells that participates in our response to infection. CD4 is also the primary receptor for the HIV virus which causes AIDS. We have discovered that a particular type of chemistry is occurring in CD4. This chemistry, which is known as redox chemistry, changes the shape of CD4. The shape change appears to be controlled by the immune cell. We have suggested that the redox chemistry in CD4 is important for controlling how immune cells res ....CD4 is a particular type of receptor on the surface of immune cells that participates in our response to infection. CD4 is also the primary receptor for the HIV virus which causes AIDS. We have discovered that a particular type of chemistry is occurring in CD4. This chemistry, which is known as redox chemistry, changes the shape of CD4. The shape change appears to be controlled by the immune cell. We have suggested that the redox chemistry in CD4 is important for controlling how immune cells respond to infection and how the HIV virus infects immune cells. Moreover, we have designed a small synthetic compound that blocks the redox chemistry in CD4 and prevents HIV infection in the test tube. We propose to investigate how the redox chemistry in CD4 controls the function of immune cells and infection by HIV.Read moreRead less
Controlling HIV-1 Replication In Macrophages: Cellular Regulation Of Tat Expression
Funder
National Health and Medical Research Council
Funding Amount
$466,500.00
Summary
Monocytes in the blood and macrophages in the tissues are the scavenger cells of the body's immune system. They are among the first cells to become infected with HIV and harbour the virus for the lifetime of the cell, which can be up to several years. While monocytes are only infected at low frequency, macrophages in tissues can be infected in high numbers and can contribute significantly to virus production. Current potent combination therapies are unable to clear the virus from these cells and ....Monocytes in the blood and macrophages in the tissues are the scavenger cells of the body's immune system. They are among the first cells to become infected with HIV and harbour the virus for the lifetime of the cell, which can be up to several years. While monocytes are only infected at low frequency, macrophages in tissues can be infected in high numbers and can contribute significantly to virus production. Current potent combination therapies are unable to clear the virus from these cells and have limited efficacy in this cell type. There are no treatments which specifically target HIV infection in these important viral reservoirs. We have found that in a laboratory model of HIV infection in macrophages, the infection changes from active and productive to chronic and non-productive over the course of several weeks. This change is characterised by a decrease in one of the virus' important regulatory proteins, Tat. In this project, we aim to determine how the cells induce this change in the virus' growth. This may lead to novel ways in which HIV could be controlled in these important cells by targeting cellular rather than viral proteins. Controlling infection in macrophages and preventing spread of the virus to other cells would assist with the problem of the virus rebounding rapidly when patients stop or interrupt therapy and would help with long term treatment and management, leading to eventual eradication of the virus from the body.Read moreRead less
Determinants Of Immune Restoration Disease And Persistent Immune Dysfunction In HIV Patients Responding To ART
Funder
National Health and Medical Research Council
Funding Amount
$445,011.00
Summary
Many people throughout the world now receive antiretroviral treatment (ART) for HIV-AIDS. ART increases numbers of CD4 T-cells, but does not restore all functions the immune system. In addition, some patients experience serious exacerbations of pre-existing secondary infections when they respond to ART. We were the first to describe these Immune Restoration Diseases and will investigate the underlying mechanisms and the causes of persistent immune deficiency here.
Mucosal Human Immunodeficiency Virus Vaccine Late Pre-clinical Evaluation
Funder
National Health and Medical Research Council
Funding Amount
$575,315.00
Summary
Despite many candidate vaccines entering clinical development for protection against HIV, none has yet been successful. This proposal centres on late preclinical development for a novel mucosal vaccine strategy for HIV, which combines a preclinically-proven approach to generating strong T cell immune responses, with an existing approach to generating broadly neutralising antibody responses to HIV. Proof of synergy between these approaches will lead directly to clinical development.
Pre-clinica Evaluation Of A Novel HIV-1 Vaccine Statrgy
Funder
National Health and Medical Research Council
Funding Amount
$528,440.00
Summary
Recently, we have designed two mucosal HIV vaccine strategies that temporary block hormone-like molecules IL-4/IL-13 at the vaccination site inducing excellent antibody and killer T cell immunity with protective efficacy in small animals. This project aims to evaluate the safety and efficacy of these novel HIV mucosal vaccines prior to clinical evaluation.
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.