An RNA Element Negatively Regulates Initation HIV-1 Reverse Transcription And Inhibits Proviral Integration
Funder
National Health and Medical Research Council
Funding Amount
$581,524.00
Summary
We recently made the discovery that the virus that causes AIDS can be potently inhibited by stimulating a specific step in the virus life cycle. Our evidence suggests this stimulation is controlled by a host factor which will be identified in this study. Its discovery would be an important step towards a new means to fight HIV 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 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.
Silent Mutations In The HIV-1 Reverse Transcriptase Selected During Antiretroviral Therapy
Funder
National Health and Medical Research Council
Funding Amount
$555,325.00
Summary
This project seeks to determine the role of silent mutations in the HIV reverse transcriptase that are selected during drug therapy in HIV infected individuals on HIV fitness, reverse transcriptase function and the emergence of drug resistance. This study will increase our understanding of the mechanisms by which the virus evades the effects of antiretrovirals and will provide a rationale for deciding on the best drug combinations for use in patients infected with specific HIV strains (clades).
Molecular Studies Of The Astrocyte Reservoir Of HIV-1 In The Central Nervous System
Funder
National Health and Medical Research Council
Funding Amount
$592,661.00
Summary
HIV infects the brain causing dementia in 10-20% patients. Strategies aimed at eradicating HIV infection fail to take into account CNS infection. Understanding the way in which HIV enters, infects and replicates in the brain is pivotal in development of drugs to prevent brain infection and dementia. Our studies have shown that HIV infection of the brain involves mechanisms distinct to those observed for blood and other organs. This study seeks to clarify such mechanisms.
Elucidating The Mechanism Of Action Of Dendrimer Nanoparticles Against HIV
Funder
National Health and Medical Research Council
Funding Amount
$559,354.00
Summary
Dendrimers are nanoparticles with highly branched structures and they are being developed as topical microbicides to prevent the sexual transmission of HIV. This study will determine how dendrimers block HIV entry into host cells so that we can design more effective inhibitors and microbicides.
Molecular Studies Of The Astrocyte Reservoir Of HIV-1 In The Central Nervous System
Funder
National Health and Medical Research Council
Funding Amount
$533,828.00
Summary
Human immunodeficiency virus type 1 (HIV-1) causes AIDS and, to date, has infected approximately 20 thousand people in Australia and more than 40 million worldwide. HIV infects the central nervous system and causes HIV associated dementia in 10-20% of patients with AIDS. Despite the introduction of highly active antiretroviral therapy the prevalence in Australia continues to rise and studies have shown that the incidence has been under represented in the South east Asian region. Infection of the ....Human immunodeficiency virus type 1 (HIV-1) causes AIDS and, to date, has infected approximately 20 thousand people in Australia and more than 40 million worldwide. HIV infects the central nervous system and causes HIV associated dementia in 10-20% of patients with AIDS. Despite the introduction of highly active antiretroviral therapy the prevalence in Australia continues to rise and studies have shown that the incidence has been under represented in the South east Asian region. Infection of the CNS has two major implications for the treatment of AIDS patients. Firstly, HIV-associated dementia is the most common cause of dementia in people under 40 and this continuing increase in the number of young adults with dementia is placing increased pressure on health resources in the community. Secondly, strategies aimed at eradicating HIV infection from AIDS patients have thus far have failed to take into account the important and unique viral reservoir present in the CNS of an infected patient. The mechanisms involved in HIV-1infection of the brain remain unclear. Understanding the mechanisms by which HIV enters, infects and replicates the brain, are pivotal to the development of regimes to prevent infection of the brain in the first instance as well as development of targeted drug therapy to prevent dementia. Our preliminary studies have shown that HIV infection of the brain involves unique HIV virus and cellular mechanism distinct to those observed for the blood and other organs. This study seeks to clarify such mechanisms. This study will contribute to a greater understanding of how HIV-1 enters the brain and causes dementia, both of which are essential to the development of new drugs to treat HIV-1 infection.Read moreRead less
The Role Of Chemokines In Establishing HIV Latency
Funder
National Health and Medical Research Council
Funding Amount
$372,049.00
Summary
Although antiviral therapy is effective in controlling HIV, therapy must be continued life-long because the virus cannot be cleared from long lived infected CD4+ T cells that are silently or latently infected. In this proposal we will explore the mechanism of how HIV can enter these resting CD4+ T-cells and establish long lived latent infection. Understanding this process may potentially lead to new strategies to cure HIV infection.
How Does A Host Cell Stimulatory Factor Stabilize The HIV-1 Reverse Transcription Complex?
Funder
National Health and Medical Research Council
Funding Amount
$631,883.00
Summary
We have identified a host cell activity which HIV uses to infect cells. The activity assists the uniques ability of HIV to convert its genome to a form which inserts itself into the host cell DNA. If we can identify the protein responsible for this activity we may be able to target it for drug development. Targetting host cell proteins rather than virus proteins for new drug may have advantages in preventing the acquisition of drug resistance.
Human immunodeficiency virus type 1 (HIV-1) causes AIDS and, to date, has infected approximately 20 thousand people in Australia and more than 40 million worldwide. People infected with HIV-1 first experience a period of 5-7 years where they remain healthy, ofter assisted by the use of anti-HIV-1 drugs, and this period is referred to as the asymptomatic period. After this period, infected individuals become sick due to their immune system being destroyed, and this is referred to as AIDS. Researc ....Human immunodeficiency virus type 1 (HIV-1) causes AIDS and, to date, has infected approximately 20 thousand people in Australia and more than 40 million worldwide. People infected with HIV-1 first experience a period of 5-7 years where they remain healthy, ofter assisted by the use of anti-HIV-1 drugs, and this period is referred to as the asymptomatic period. After this period, infected individuals become sick due to their immune system being destroyed, and this is referred to as AIDS. Research into how HIV-1 causes AIDS has shown us that the virus changes over time to make itself better able to kill cells of the immune system, by at least 2 mechanisms. The first mechanism, which is the best characterised one, is where the virus changes the way it infects cells, whereby it can infect many more cells in the body by taking advantage of an alternate receptor molecule on the cell called CXCR4. This molecule is very widely expressed on immune cells, and thus the virus can now infect and kill many more cells. However, in about 50% of infected people who eventually get AIDS, the virus does not change this way. The virus instead uses it's original receptor to infect cells, called CCR5. Our preliminary studies, as well as other published reports, suggest that the virus changes itself another way to make it kill immune cells better, without using CXCR4. However, the mechanism by which HIV-1 does this is poorly understood. This proposal aims to better understand this mechanism. We expect to find that, in this group of patients, the Env proteins on the virus change to be able to bind CCR5 more tightly, and thus be able to use fewer molecules of CCR5 to infect cells. We believe that these forms of the virus are now better able to kill immune cells, leading to AIDS. This study will contribute to a greater understanding of how HIV-1 causes AIDS, which is necessary for the development of new drugs to treat HIV-1 infection.Read moreRead less