Viral And Cellular Factors Affecting Early Steps In HIV Reverse Transcription
Funder
National Health and Medical Research Council
Funding Amount
$465,750.00
Summary
One of the key events in the life cycle of HIV is the conversion of viral RNA into a double stranded DNA intermediate. This process, called reverse transcription, is carried out by the viral enzyme reverse transcriptase (RT) in conjunction with other viral and cellular factors. While HIV RT has been extensively studied and RT inhibitors have been used in anti-retroviral therapy for HIV patients, other viral and cellular factors essential for efficient HIV reverse transcription have not been prop ....One of the key events in the life cycle of HIV is the conversion of viral RNA into a double stranded DNA intermediate. This process, called reverse transcription, is carried out by the viral enzyme reverse transcriptase (RT) in conjunction with other viral and cellular factors. While HIV RT has been extensively studied and RT inhibitors have been used in anti-retroviral therapy for HIV patients, other viral and cellular factors essential for efficient HIV reverse transcription have not been properly investigated and may represent a new class of anti-HIV targets.This project, based on our long standing (>10 years) research interest and experience, aims at identification of the viral and cellular factors particularly involved in the early steps of HIV reverse transcription.We have obtained preliminary data which lead to hypotheses regarding what kind of viral and cellular factors might be involved and their possible modes of action. Experiments have been designed to specifically prove or disprove these hypotheses. Thus this project will help us achieve a more comprehensive understanding on how HIV uses other viral and cellular factors, in addition to RT, to accomplish one of the mandatory stage of its growth (reverse transcription); and identify viral and cellular factors which can be further explored as new targets for anti-retroviral therapy. This is particularly important, as HIV resistance to current drug therapy has emerged as one serious issue facing HIV patients, and the HIV care communities.Read moreRead less
Gene therapy is a novel form of medical treatment in which healthy genes are used to replace defective genes in cells. It is sobering to realise that in the next few years the whole human DNA sequence will be known. Consequently the already large list of genes which are known to cause disease will be greatly expanded through the application of molecular genetics. Surprisingly, however, treatments based on the correction of disease genes in the cells of a patient are not keeping up with expectati ....Gene therapy is a novel form of medical treatment in which healthy genes are used to replace defective genes in cells. It is sobering to realise that in the next few years the whole human DNA sequence will be known. Consequently the already large list of genes which are known to cause disease will be greatly expanded through the application of molecular genetics. Surprisingly, however, treatments based on the correction of disease genes in the cells of a patient are not keeping up with expectations. In attempting to achieve clinically relevant results, viruses (masters of forcing infected cells to do their bidding) have been harnessed to deliver healthy genes into diseased cells. The problem has been that the modified, safe viruses used clinically have not been efficient at achieving sustained production of healthy genes in sufficient numbers of cells. In the studies described , we will attack this problem using a number of different, but complementary approaches. Our main focus will be to facilitate efficient virus entry of appropriate target cells. We have recently been successful in cloning the receptors for two important viruses which can enter human cells. Identification of these receptors gives us clues to methods of improving virus entry. Now that we know the identity of these receptors, we can create tools to define the type of cells that these viruses can readily target.Read moreRead less
Analysis And Manipulation Of The Genome-wide Integration Signatures Of Gamma-retroviral And Lentiviral Vectors In Human Haematopoietic Stem Cells
Funder
National Health and Medical Research Council
Funding Amount
$612,154.00
Summary
Gene therapy has been successful in treating several diseases involving the bone marrow, but has been associated with the development of leukaemia in a number of patients. The cause has been tracked to the gene transfer technology used and associated damage to the genetic blueprint of treated cells. In this study we plan to use high-throughput genetic analysis to better understand the nature of this damage and to develop strategies to improve the safety of the gene repair process.
HTLV-1 is a lifelong infection of immune cells that sustains high infection rates up to 45% in key Australian communities. Despite HTLV-1 causing serious malignancy and inflammatory co-morbidities that shorten lifespan, few biomedical interventions are available. We will examine how the virus grows and alters immune responses to cause disease. With this, we can develop antiviral treatments to reduce virus infected cells, and make new diagnostic biomarker assays suitable for remote settings.