Genes Of Mycobacterium Tuberculosis Essential For Latent Tuberculosis Infection
Funder
National Health and Medical Research Council
Funding Amount
$590,103.00
Summary
One third of the worlds population is latently infected with M. tuberculosis, the bacteria which causes TB. We have identified key genes in M. tuberculosis that enable the bacterium to shut-down and become latent. This project will investigate these genes, identify their role and yield vital information for a new paradigm of drug and vaccine development. Improved vaccines and drugs which can target and inhibit latency would be of enormous benefit to the global community.
Pro-apoptotic Therapies For The Treatment Of Mycobacterium Tuberculosis Disease And Latent Infection
Funder
National Health and Medical Research Council
Funding Amount
$140,949.00
Summary
Programmed cell death has an important role in our ability to fight organisms. Upon infection, processes result in activation of death-inducing cascades, resulting in death of cell and pathogen. M. tuberculosis, an escalating health problem, has developed mechanisms to prevent this, leading to latency. This study, which uses mouse M.tb models, hypothesises that reversal of these mechanisms, using drugs currently in trial in leukaemia (ABT-737 & BV6), may lead to clearance of infection.
Understanding The Role Of Ongoing Viral Activity In Herpes Simplex Virus Latency
Funder
National Health and Medical Research Council
Funding Amount
$980,762.00
Summary
The virus that causes cold sores and genital herpes has a dormant phase from which renewed infection can recur. We recently discovered that this dormant phase is more active than we thought and we now want to learn how the body acts to suppress the virus so that these defence mechanisms might be improved to stop recurrent infections.
The Impact Of HIV Integration Sites On Eliminating HIV Latency
Funder
National Health and Medical Research Council
Funding Amount
$778,313.00
Summary
Current antiviral therapy for HIV controls virus production and allows recovery but does not eliminate the silent infection that prevents complete virus elimination and cure. We will examine two ways that HIV can silently infect T cells for differences in the sites at which the HIV DNA inserts into the genome. We will examine the way in which these differences at the genomic level may limit the ability to activate and eliminate persistent infection in memory T cells.
The Role Of Chemokine Signalling In Maintenance Of The Latent HIV Reservoir
Funder
National Health and Medical Research Council
Funding Amount
$92,161.00
Summary
HIV cure research aims to eliminate cells with HIV in their DNA. These cells have higher levels of a receptor, CCR6, signalling through which causes migration to and concentration in the gut. This gut migration may help to maintain the HIV reservoir by bringing susceptible cells close to infected cells. We will assess the effect of blocking CCR6 signalling on the ability to infect these cells with HIV in the laboratory and its effect on the reservoir of an analogous virus in macaques.
Mechanisms Of Immune Modulation By Human Cytomegalovirus During The Latent Phase Of Infection
Funder
National Health and Medical Research Council
Funding Amount
$165,500.00
Summary
Human cytomegalovirus (CMV) is a herpesvirus which infects a majority of the population. CMV is a significant cause of serious, life-threatening disease in neonates and in people who are immunosuppressed. Bone marrow and solid organ transplant recipients are particularly at risk of developing serious CMV disease. CMV has the remarkable ability to hide in the body in a dormant or latent form for the life of the host. However, when conditions are right the virus can awaken (ie reactivate) from its ....Human cytomegalovirus (CMV) is a herpesvirus which infects a majority of the population. CMV is a significant cause of serious, life-threatening disease in neonates and in people who are immunosuppressed. Bone marrow and solid organ transplant recipients are particularly at risk of developing serious CMV disease. CMV has the remarkable ability to hide in the body in a dormant or latent form for the life of the host. However, when conditions are right the virus can awaken (ie reactivate) from its latent state, producing new infectious virus and disease. It is in immunosuppressed individuals such as transplant patients that reactivation from latency is of most medical significance, yet the latent phase of infection remains very poorly understood. We recently reported that during latent infection CMV interfered with the expression of a protein which plays a crucial role in our immune system. This protein is called MHC class II and its proper function is essential for our immune system to fight infections. Thus, we postulated that the ability of CMV to successfully hide in a cell in a latent state is at least partially due to its ability to interfere with the cells ability to properly make MHC class II proteins. This project aims to futher define and characterise the functions of latent CMV that enable it to interfere with our immune system. Firstly, we aim to continue with our studies to determine the mechanism by which latent CMV interferes with MHC class II expression. Secondly, we will seek to determine whether latent CMV interferes with any other important components of our immune system. Thirdly, we will seek to identify the precise viral gene that causes the interference with MHC class II expression. Determining the mechanism of immune system regulation and the viral gene(s) responsible for this interference may lead to the design of gene therapies to lessen the clinical impact of CMV disease in transplant recipients.Read moreRead less