RNA viruses are one of the last frontiers for globally significant infections. There ability to rapidly hide from the host's immune response and cause additional infections has made the ability to make vaccines very difficult. By studying patients that naturally and rapidly clear multiple infections we have identified strategies to conquer these highly divergent viruses. We are currently dedicated to trying to understand how we can mold this knowledge into a protective vaccine.
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.
Innate Immune Functions Of The Intracellular Antibody Receptor TRIM21
Funder
National Health and Medical Research Council
Funding Amount
$408,768.00
Summary
The immune system can fight viral infections with antibodies, which mark viruses outside of cells for elimination by immune cells. Antibody-coated viruses try to escape elimination by hiding inside cells. This project will determine how immune cells recognise the antibody-coated viruses ‘hiding’ within them, and the defence response they launch to eliminate viral infection. Such knowledge may allow us to develop better anti-viral drugs and vaccines to fight viral diseases like the common cold.
Herpesviruses infect most Australians and cause recurrent ulcers, birth defects and cancer. Infection lasts lifelong, and spreads to close contacts without obvious clinical signs. Thus disease is hard to prevent. However we can learn much from related animal infections. We have shown that both mouse and human herpesviruses enter mice via cells in the nose. Thus human infections might follow the same route. We will define what body defences work here and whether vaccines can prevent infection.
Even in well-resourced countries, the ability to continue treating HIV patients for their lifetime may become unaffordable, which has focused attention on developing a cure for HIV. We have exploited unique insights into a pathway for Tat expression from latent HIV to identify novel compounds that target HIV latency. This project assembles a multidisciplinary team to optimize the lead compounds, and develop novel drug regimens to fast-track into clinical development as a HIV-curative therapy.
Human ?-herpesviruses persist for life, cause cancers and emerge with particular virulence when the immune system is weak. Vaccination against them is therefore an important health priority. We have shown for a related ?-herpesvirus of mice that live vaccines protect. Antibody seems to play a major role. We will test whether safer, recombinant vaccines are also sufficient to elicit protective antibody. Thus we can establish a viable strategy for preventing virus-induced human cancers.
Cells of the macrophage lineage, the immune system's scavenger cells which attack invading organisms and other infected cells, are important targets of HIV infection, are among the first cells to become infected when the virus is transmitted from person to person and serve as reservoirs of the virus throughout disease progression. Monocytes in the blood, the precursers to macrophages in the tissues, are not very susceptible to infection with HIV but we and others have shown that small numbers ar ....Cells of the macrophage lineage, the immune system's scavenger cells which attack invading organisms and other infected cells, are important targets of HIV infection, are among the first cells to become infected when the virus is transmitted from person to person and serve as reservoirs of the virus throughout disease progression. Monocytes in the blood, the precursers to macrophages in the tissues, are not very susceptible to infection with HIV but we and others have shown that small numbers are infected throughout an infected person's life and that they remain infected despite years of treatment with potent combination drug therapies which reduce the amount of virus in the blood to undetectable levels. We have evidence that suggests that a certain subset of monocytes may be preferentially infected with HIV and may contribute significantly to its persistence in the body. This subset is known to be expanded in response to certain infections, probably including HIV, and during inflammation. We have shown that these cells accumulate in the brains of HIV-infected people especially those with AIDS related dementia. In this project we will characterise these cells in the blood and test our hypothesis that ongoing infection in this subset of monocytes plays an important role in the course of HIV disease and contributes to the persistence of HIV infection and the failure of currently available therapies to eradicate it.Read moreRead less
Antiviral therapy for HIV infection has substantially reduced mortality but HIV can't be cured. This is because HIV causes a silent or latent infection in some cells. This grant will investigate a new class of drugs which show promise in reversing latent infection and potentially eliminating HIV from infected patients
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.
The Adaptive Immune Response To Epstein-Barr Virus.
Funder
National Health and Medical Research Council
Funding Amount
$92,314.00
Summary
Epstein-Barr virus (EBV), the causative agent of glandular fever, is carried by a large proportion of adults worldwide. EBV is known to cause many cancers including Burkitt's lymphoma and has been linked to autoimmune diseases such as multiple sclerosis. The aim of this project is to find new fragments of EBV that the body's immune system can recognise and use to protect itself against the virus. Once found these pieces will form parts of the puzzle that will one day combine as a vaccine against ....Epstein-Barr virus (EBV), the causative agent of glandular fever, is carried by a large proportion of adults worldwide. EBV is known to cause many cancers including Burkitt's lymphoma and has been linked to autoimmune diseases such as multiple sclerosis. The aim of this project is to find new fragments of EBV that the body's immune system can recognise and use to protect itself against the virus. Once found these pieces will form parts of the puzzle that will one day combine as a vaccine against EBV.Read moreRead less