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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
Our centre combines clinical and laboratory expertise to tackle autoimmune, inflammatory, and immune deficiency diseases. Starting from a genetic discovery platform, we aim to understand precisely how the immune system goes wrong in each individual patient to cause disease. This approach will make diagnoses more accurate and tailor treatment to each patient. The centre's approach should provide a template for the implementation of genomics and personalized medicine into routine clinical practice
It is feasible to sequence patient genomes but we need to know more about how genetic variants cause complex disease. We have sequenced genomes from patients with immune deficiency and will test the idea that genetic variation causes consistent changes in particular white blood cells, thus providing a bridge between genomic information and clinical diagnosis. Outcomes will include more accurate diagnosis, better understanding of immunity, and a strategy for using whole genome information.
Arbovirus Activation And Modulation Of NLRP3 Inflammasome
Funder
National Health and Medical Research Council
Funding Amount
$779,720.00
Summary
This project aims to establish how mosquito borne viruses such as Ross River and dengue viruses interacts with the human host to cause disease, including how the virus evades the host’s immune response to persist and cause disease for prolonged periods. Knowing how differences in the virus and the host’s immune system interplay to cause asymptomatic to severely disabling disease will assist in devising new treatments and prevention programs to lessen the impact of these diseases in Australia.
New Insights Into Viral Inflammatory Disease Mechanisms And Approaches To Therapy
Funder
National Health and Medical Research Council
Funding Amount
$631,010.00
Summary
This fellowship aims to establish how viruses cause disease, including how they evade the immune response to persist and cause disease for prolonged periods. My vision is that knowing how the virus and the immune system interact to determine disease severity will assist in devising new treatments and prevention programs to lessen the impact of viral diseases in Australia and worldwide.
RNAi Therapeutic Intervention Of Human Viral Respiratory Disease
Funder
National Health and Medical Research Council
Funding Amount
$584,117.00
Summary
Human metapneumovirus (HMPV), causes clinical disease that is very similar to human respiratory syncytial virus (RSV) and co-circulates with RSV. HMPV is emerging as a major cause of morbidity and life-threatening respiratory tract disease in infants, young children and the elderly worldwide. No treatment is currently available. The objectives of this proposal are to develop novel antiviral drugs that silence the expression of viral genes and to examine protection against the disease.
Mosquito-borne alphaviruses such as Ross River and chikungunya viruses cause widespread epidemics and exert extreme pressure on the public health systems of affected regions. Alphaviruses spreads to joints and triggers a severe disease in those affected. There are no effective treatments or vaccines. The project will investigate virus-host interaction at the bite site. The outcome will be new knowledge to treat infection at the mosquito bite site to prevent joint disease.
Mechanism/s Of Disease Caused By Respiratory Viral Infections
Funder
National Health and Medical Research Council
Funding Amount
$479,517.00
Summary
A newly discovered respiratory virus, human metapneumovirus (HMPV), causes clinical disease that is very similar to human respiratory syncytial virus (RSV) and co-circulates with RSV. Human RSV is a major cause of morbidity and life-threatening respiratory tract disease in infants and young children worldwide, and is recognised as an important respiratory pathogen in elderly adults and immune compromised patients. The recent isolation of HMPV from children hospitalised with respiratory tract ill ....A newly discovered respiratory virus, human metapneumovirus (HMPV), causes clinical disease that is very similar to human respiratory syncytial virus (RSV) and co-circulates with RSV. Human RSV is a major cause of morbidity and life-threatening respiratory tract disease in infants and young children worldwide, and is recognised as an important respiratory pathogen in elderly adults and immune compromised patients. The recent isolation of HMPV from children hospitalised with respiratory tract illness similar to RSV, but with an unknown etiology, suggests that HMPV may mediate similar clinical pathology. Nothing is currently known about the immune response to HMPV, or the association of these responses with lung disease. The objectives of this proposal are to elucidate the mechanisms of immunity and disease pathogenesis associated with human metapneumovirus (HMPV) and to investigate the use of a novel vaccine to protect against HMPV infection. Once this data is obtained, the study will provide the foundation for further research in the development of vaccines or therapeutic protocols to treat HMPV. It will also provide valuable information for understanding the disease in humans. Also,it is likely that HMPV, like hRSV, may prove to be an agent associated with long-term decreased pulmonary function and airflow limitation perhaps developing to asthma.Read moreRead less
Novel Insights Into The Pathobiology Of Alphavirus Infections
Funder
National Health and Medical Research Council
Funding Amount
$827,660.00
Summary
Infections with mosquito-borne viruses are increasing at an alarming rate worldwide. Ross River virus is endemic in parts of Australia, PNG and Pacific islands, while chikungunya virus is distributed globally and causes recurrent pandemics that involve millions of people. These viruses cause severe musculoskeletal disease for several months after infection. This project aims to establish how these viruses interact with the human host to cause disease and may provide a basis for new treatments.