Defining The Interaction Of HIV With The Interferon System In Initial Mucosal Infection
Funder
National Health and Medical Research Council
Funding Amount
$867,716.00
Summary
Very early after virus exposure, immune cells secrete interferons that help limit the spread of viruses within the body. We will investigate the complex interplay between HIV and the interferon system, especially how HIV inhibits the early induction of interferon to aid its spread and then how the body later restores the interferon response. We will also examine how HIV manipulates the interferon system in order to persistent latent reservoirs within tissues.
Mechanisms Of HIV Binding, Uptake, Trafficking And Infection In Dendritic Cells
Funder
National Health and Medical Research Council
Funding Amount
$144,250.00
Summary
HIV is the fourth greatest killing disease in the world. Currently there are more than 40 million people infected with the virus and it is spreading through Asia, especially India and China. The priorities are vaccines and new antiviral strategies to complement the existing ones and provide alternatives in the event of toxicity and viral resistance to existing drugs. HIV infects three types of body cells, CD4 lymphocytes, macrophages and dendritic cells. Dendritic cells are the key cells which n ....HIV is the fourth greatest killing disease in the world. Currently there are more than 40 million people infected with the virus and it is spreading through Asia, especially India and China. The priorities are vaccines and new antiviral strategies to complement the existing ones and provide alternatives in the event of toxicity and viral resistance to existing drugs. HIV infects three types of body cells, CD4 lymphocytes, macrophages and dendritic cells. Dendritic cells are the key cells which normally act as sentinels at the surfaces of the body picking up microbes digesting them and transferring their products to lymph nodes where the immune response is stimulated. HIV uses this pathway to enter the body and particularly to enter CD4 lymphocytes and lymph nodes and undergo explosive replication. This project is aimed at identifying new proteins which the virus uses to bind to these cells and also the pathways which the virus uses within the cells to be transferred to CD4 lymphocytes. Such knowledge should allow the design of new antiviral strategies and may also assist in developing HIV vaccines.Read moreRead less
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.
HIV Assembly, Transport, Egress And Transfer From Infected Dendritic Cells
Funder
National Health and Medical Research Council
Funding Amount
$511,629.00
Summary
HIV-AIDS is the fourth leading killing disease worldwide, with the disease burden shifting towards women. Study of the HIV life cycle in cells known to be targetted during HIV transmission is key towards designing additional preventative measures in the form of topical gels known as microbicides. Mapping of the basic pathways of viral transport within such cells, will aid further drug discovery and-or appropriateness of use of existing drugs in microbicide formulations.
Current anti-HIV therapies can't cure HIV because HIV remains silent(latent) in long-lived cells. The HIV life cycle and virus production is linked to activation of the host cell, which is regulated by dendritic cells. This grant will explore how the factors controlling T cell activation and proliferation control virus expression and latency. By understanding how latent infection is established and maintained, these studies will potentially identify new ways to eliminate HIV infection.
Pathogenesis Of Persistent Human Virus Infections Of Global Significance
Funder
National Health and Medical Research Council
Funding Amount
$6,571,328.00
Summary
The study will investigate why humans cannot eradicate particular viruses (HIV-AIDS, cytomegalovirus and herpes simplex virus), the long term effects of these viruses and ways to improve control. Current treatments can only partly suppress the levels of these viruses, because they persist in certain parts of the body called reservoirs, only to resurge later causing disease. Thus, the overall aim of the research program is to discover the mechanisms by which these viruses are able to successfully ....The study will investigate why humans cannot eradicate particular viruses (HIV-AIDS, cytomegalovirus and herpes simplex virus), the long term effects of these viruses and ways to improve control. Current treatments can only partly suppress the levels of these viruses, because they persist in certain parts of the body called reservoirs, only to resurge later causing disease. Thus, the overall aim of the research program is to discover the mechanisms by which these viruses are able to successfully persist within reservoirs in the human body. The research program brings together a group of 6 leading scientists and clinicians located at 3 sites in 2 Australian cities. The team is comprised of experts in the study of HIV-AIDS, cytomegalovirus and herpes simplex virus who will combine their knowledge and expertise to speed up the process of research on these viruses that are of major health importance. Studies will also utilise a number of cutting edge technologies that now make it possible to much more rapidly and precisely determine how viruses cause disease. Advances in our understanding of how viruses persist may form the basis for treatments aimed at controlling persistent infections and the serious diseases caused by these viruses.Read moreRead less
Herpes Simplex Virus Type 2 Modulates The HIV-1 Infection Of Plasmacytoid And Myeloid Dendritic Cells.
Funder
National Health and Medical Research Council
Funding Amount
$76,637.00
Summary
The aim of my project is to find out why people with herpes simplex virus are more susceptible to HIV infection. Herpes simplex is a common sexually transmitted disease and causes genital ulcers in both men and women. Understanding how the immune system responds to these two viruses will help to reduce heterosexual spread of HIV.
HIV-1 Transcriptional Gene Silencing By Promoter Targeted Si/shRNAs: Uncovering Mechanisms, Optimising Delivery Systems, Assessing In Vivo Efficacy.
Funder
National Health and Medical Research Council
Funding Amount
$641,789.00
Summary
Current therapy for HIV is effective but must be taken for life. If therapy is stopped the virus comes back immediately from reservoirs not affected by current drugs. These fluctuating levels of virus are associated with increased illness and death. We are exploring a method of inducing prolonged viral latency using short double stranded RNA molecules. We propose to understand the mechanism of action of these possible therapeutics and to develop these constructs towards use in clinical trials.
Identifying Molecular Machinery In Dendritic Cells.
Funder
National Health and Medical Research Council
Funding Amount
$687,500.00
Summary
Vaccines invoke immune responses that will protect a vaccinated host if they encounter infection. Vaccines can also be deployed to fight cancer. 'Dendritic cells' are the key immune cell responsible for vaccine immunity. While dendritic cells are pivotal to initiating vaccination, little is known about their internal machinery. This research proposal will identify new machinery for dendritic cell vaccine immunity that will serve as therapeutic targets to boost vaccination.