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.
The Role Of CXCR3 Chemokines In Hepatitis C And Other Forms Of Viral Hepatitis
Funder
National Health and Medical Research Council
Funding Amount
$457,267.00
Summary
The majority of individuals infected with hepatitis C virus (HCV) show a slow progression of liver disease over a period of 10-20 years. This liver disease is primarily a result of the host immune response to liver cells (hepatocytes) infected with HCV. As part of this immune response there in an increase in the number of immune cells that infiltrate the liver. To date we do not fully understand the mechanims that attract these cells to the liver but a class of molecules called chemokines is the ....The majority of individuals infected with hepatitis C virus (HCV) show a slow progression of liver disease over a period of 10-20 years. This liver disease is primarily a result of the host immune response to liver cells (hepatocytes) infected with HCV. As part of this immune response there in an increase in the number of immune cells that infiltrate the liver. To date we do not fully understand the mechanims that attract these cells to the liver but a class of molecules called chemokines is the most likely candidate. Thus a greater understanding of the chemokines expressed in the liver, their modulation and role in attracting immune cells to the liver in HCV-related liver disease will help us understand the basic mechanisms of liver disease with the possibility of development of novel therapeutic strategies. In pilot studies we have shown that the chemokine interferon-inducible T cell alpha chemoattractant (I-TAC) is significantly increased in the liver of persons infected with HCV. I-TAC is a member of the CXCR3 ligand chemokine family that attracts lymphocytes to sites of inflammation and as such may play an important role in hepatitis C. We have also shown that hepatocytes express I-TAC and that HCV can upregulate expression of I-TAC in a laboratory model of HCV replication. This proposal plans to determine the molecular mechanisms of I-TAC expression in response to HCV replication and to investigate if I-TAC expression is unique for hepatits C or a general feature of viral infections of the liver. We also plan to determine the the role of I-TAC and other CXCR3 ligand family members in a mouse model of viral hepatitis through the use of CXCR3 ligand antagonists. These experiments will enhance or knowledge of the role of the CXCR3 ligands in hepatitis C and viral hepatitis in general.Read moreRead less
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.
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
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
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.