The Role Of Dendritic Cells In Sexual Transmission Of HIV And Viral Reservoir Formation
Funder
National Health and Medical Research Council
Funding Amount
$654,296.00
Summary
This grant aims to determine the subsets of dendritic cells found in the different tissue of the anogenital tracts and to determine which ones play the key roles in HIV transmission. The relative ability of these cells to transfer the virus to activated T cells leading to productive infection and resting memory T cells leading to latent infection will be investigated. Finally the key receptors which mediate this process will be determined and strategies to block this transfer developed.
Elucidation Of Immune Mechanisms Underlying HSV Vaccine Development
Funder
National Health and Medical Research Council
Funding Amount
$573,993.00
Summary
HSV-1 and -2 causes genital herpes, cold sores, encephalitis, potential fatal neonatal herpes, keratitis and blindness as well as severe disease in transplant patients. HSV infection also enhances the acquisition of HIV by 2-3 fold. Investigating the mechanism of immune response to HSV infection or components of HSV will assist in understanding immune control of HSV, HSV vaccine development, and assist in reducing in HIV spread.
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
Discovery Of A Novel Immune Evasion Strategy Employed By Mosquito Borne Viruses To Suppress Antiviral Immune Responses
Funder
National Health and Medical Research Council
Funding Amount
$418,642.00
Summary
The transition from mosquitoes, ticks, or other invertebrate vectors to the human hosts represents a crucial step in the successful establishment of arthropod borne viruses (arboviruses). The incidence of arbovirus infections such as dengue virus, West Nile virus, Ross River virus is increasing at an alarming rate in various parts of the world. In addition, the emergence of new viruses resulting in significant mortality in the population is of utmost concern. Vaccines for many of these viruses r ....The transition from mosquitoes, ticks, or other invertebrate vectors to the human hosts represents a crucial step in the successful establishment of arthropod borne viruses (arboviruses). The incidence of arbovirus infections such as dengue virus, West Nile virus, Ross River virus is increasing at an alarming rate in various parts of the world. In addition, the emergence of new viruses resulting in significant mortality in the population is of utmost concern. Vaccines for many of these viruses remain elusive. One factor that contributes to this is the ability of viruses to develop ingenious strategies to avoid or suppress the host defence systems, which enable its successful establishment in the host. Understanding how viruses evade-suppress host defence machinery will certainly enhance and improve our approaches to fight them. For the first time internationally we have discovered a new and novel pathway employed by arboviruses to suppress antiviral immune responses in the host. We have discovered that naturally occurring carbohydrates on viruses derived from mosquito cells, would influence these virus s ability to evade-suppress host antiviral proteins such as interferons. This may be a general effect of arboviruses or may even extend to other viruses , which include a number of deadly pathogens (HIV, Influenza). This research has the potential to significantly expand our understanding of how these viruses establish infection and cause disease. Also this discovery has broader implications for understanding inflammatory processes and their regulation.Read moreRead less
Understanding How Cytomegaloviruses Establish Systemic Infection
Funder
National Health and Medical Research Council
Funding Amount
$668,144.00
Summary
Human cytomegalovirus (HCMV) infects most Australians, causes birth defects and harms transplant patients. Vaccines against it have worked poorly. HCMV spreads throughout the body and is never cleared. To control infection we must identify its key checkpoints. Using mouse CMV, we find that host dendritic cells, which normally defend against infections, are taken over and spread virus to new sites. The viral gene responsible is a potential target for intervention. We will define how it works.
Targeting Myeloid Cells To Restrict Gamma-herpesvirus Spread
Funder
National Health and Medical Research Council
Funding Amount
$643,152.00
Summary
Gamma-herpesviruses infect most people and cause cancers. Vaccines to date have worked poorly. We have identified a key role for myeloid cells in infection that suggests a new approach. Interferons restrict infection in some myeloid cells. We will test whether inducing interferons can make all myeloid cells restrictive and reduce chronic infection. We will test then whether myeloid-restricting antibodies can recruit the same defences to provide a basis for vaccination.
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.
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
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.