The Role Of HIV Infection Of Astrocytes In The Development Of HIV Associated Dementia
Funder
National Health and Medical Research Council
Funding Amount
$144,250.00
Summary
Dementia is an extremely common problem in the late stages of Human Immunodeficiency Virus (HIV) infection. HIV-associated dementia is the most common cause of dementia in people under 40 years of age. Despite the development of very good drugs to attack the virus, HIV-associaed dementia continues to be a major clinical problem. We are looking at the reasons why some people infected with HIV become demented and others do not. We are also looking at how best to prevent the development of dementia ....Dementia is an extremely common problem in the late stages of Human Immunodeficiency Virus (HIV) infection. HIV-associated dementia is the most common cause of dementia in people under 40 years of age. Despite the development of very good drugs to attack the virus, HIV-associaed dementia continues to be a major clinical problem. We are looking at the reasons why some people infected with HIV become demented and others do not. We are also looking at how best to prevent the development of dementia. We believe that astrocytes (an important brain cell that supports neurons) play a very important role in the development of HIV-associated dementia. With an improved understanding of the steps leading to dementia we can better plan treatments to prevent the development of this devastating complication of HIV-AIDS.Read moreRead less
Macfarlane Adaptive Changes In HIV-1 Subtype C Envelope Glycoproteins Contributing To Pathogenicity.
Funder
National Health and Medical Research Council
Funding Amount
$310,787.00
Summary
HIV exists as multiple subtypes. The most commonly studied is type B (B-HIV). B-HIV is common in developed countries, but accounts for only a small fraction of HIV infections worldwide. Type C HIV (C-HIV) in Africa and Asia accounts for the majority of infections worldwide, yet very little is known about how C-HIV causes AIDS. We aim to understand how C-HIV causes AIDS. This is critical for development of drugs and vaccines specifically designed for those who are most urgently need.
Drug Resistance Mutations In The Connection Subdomain Of The HIV-1 Reverse Transcriptase
Funder
National Health and Medical Research Council
Funding Amount
$376,710.00
Summary
Human immunodeficiency virus type 1 (HIV-1) infections can be controlled with antiretroviral drugs. In the majority of patients on antiretroviral therapy the virus mutates and is no longer inhibited by the drug. The emergence of drug-resistant HIV-1 is one of the major factors that lead to loss of drug efficacy in patients. Mutations that confer drug resistance have been defined and are specific for different drug classes. Genotype assays that are used to predict drug resistance are routinely us ....Human immunodeficiency virus type 1 (HIV-1) infections can be controlled with antiretroviral drugs. In the majority of patients on antiretroviral therapy the virus mutates and is no longer inhibited by the drug. The emergence of drug-resistant HIV-1 is one of the major factors that lead to loss of drug efficacy in patients. Mutations that confer drug resistance have been defined and are specific for different drug classes. Genotype assays that are used to predict drug resistance are routinely used to guide therapeutic decisions in the treatment of HIV-1 infected individuals. For drugs that target the HIV-1 reverse transcriptase (RT), commonly used genotype kits normally analyse mutations in the first 240 out of 560 amino acids of the reverse transcriptase. This ignores the impact of mutations in other regions of the enzyme, which are potentially important in drug resistance. Recently, mutations that inhibit ribonuclease H function of the HIV-1 RT have been shown to confer high-level resistance to zidovudine, providing the precendent that mutations beyond codon 240 can confer drug resistance. Our analysis of a different region to ribonuclease H called the connection subdomain has demonstrated the presence of mutations that are highly prevalent in drug-treated versus drug naive patients. In this study we will use in vitro assays to define the effect of these mutations on drug resistance and viral fitness . We will also determine the mechanism by which these mutations confer drug resistance. Finally, using our unique database consisting of over 20,000 genotyped samples , we will establish the role of these mutations in the patient. This study is anticipated to identify clinically significant mutations that are present in the RT connection subdomain. Additionally, this study will lead to the development of more accurate genotype assays which will improve the clinical management of HIV infected individuals.Read moreRead less
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
Inhibition Of Nef-activated Src-family Kinases By CHK
Funder
National Health and Medical Research Council
Funding Amount
$514,307.00
Summary
HIV hijacks infected blood cells to produce its own proteins. Nef is one of these proteins and Nef alone is sufficient to cause an AIDS-like disease. Recently, we discovered that a protein called CHK can inhibit Nef. Our research will determine how CHK inhibits Nef and test the feasibility of drugs based on CHK. Such drugs would slow AIDS progression, assisting conventional therapies and patients' immune systems to combat the infection, leading to longer, healthier, more productive lives.