Analysis Of The Role Of Rotavirus Infection In Development Of Type 1 Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$348,875.00
Summary
Our earlier studies in children with a family history of type 1 diabetes have shown that infection with a common virus, rotavirus, may be one factor contributing to their progression to diabetes. Rotavirus is the most common cause of diarrhoea, vomiting and dehydration in young children, and it was thought that rotavirus infection is usually confined to the intestine. To understand how rotavirus infection might promote diabetes, my group has developed a mouse model. Using mice for these studies ....Our earlier studies in children with a family history of type 1 diabetes have shown that infection with a common virus, rotavirus, may be one factor contributing to their progression to diabetes. Rotavirus is the most common cause of diarrhoea, vomiting and dehydration in young children, and it was thought that rotavirus infection is usually confined to the intestine. To understand how rotavirus infection might promote diabetes, my group has developed a mouse model. Using mice for these studies allows us to control infection and completely analyse the results of infection, which we cannot do in humans. A type of mouse that is very likely to develop type 1 diabetes in its first 6 months of life is infected by mouth with rotavirus. We have shown that these mice develop diabetes 7 weeks faster than the same type of mice that are not given virus. In this project, we will determine the effects of mouse age, virus strain, the number of times infection occurs, and levels of virus growth in the intestine or pancreas on virus-induced diabetes acceleration. The ability of treatments for rotavirus infection, and vaccination against rotavirus, to block this accelerated diabetes also will be tested. We expect that rotavirus will be found growing in the pancreas, that virus growth is necessary for diabetes acceleration, and that prevention of rotavirus infection will also prevent the rapid diabetes onset. This model could prove to be suitable for testing the effectiveness and safety of new drugs and vaccines against both rotavirus and type 1 diabetes. Our studies will be crucial in determining the importance of rotavirus infection in the development of type 1 diabetes.Read moreRead less
Modulation Of Type 1 Diabetes Development By Rotavirus Infection
Funder
National Health and Medical Research Council
Funding Amount
$413,775.00
Summary
Rotavirus is the main cause of severe diarrhoea in children, and may contribute to progression to type 1 diabetes. We have now shown that rotavirus also modulates diabetes in mice, by a novel mechanism. In this project, the mechanism of this process will be elucidated and the capacity of human rotavirus to affect diabetes will be determined. This study will help determine the design of further human studies, and whether rotavirus vaccines also are possible modulators of diabetes development.
Roles Of Integrins In Rotavirus Cell Attachment, Entry And Tropism
Funder
National Health and Medical Research Council
Funding Amount
$339,480.00
Summary
In this project, we aim to discover how rotavirus, the main cause of infantile gastroenteritis, attaches to the surface of cells. Previously, we have shown that rotavirus binds to certain members of the integrin family of proteins on the cell surface. These proteins are intimately involved in cell adhesion, movement, communication and growth. We will continue studies aimed at identifying at the molecular level the requirements for rotavirus interactions with these integrins. It will also be dete ....In this project, we aim to discover how rotavirus, the main cause of infantile gastroenteritis, attaches to the surface of cells. Previously, we have shown that rotavirus binds to certain members of the integrin family of proteins on the cell surface. These proteins are intimately involved in cell adhesion, movement, communication and growth. We will continue studies aimed at identifying at the molecular level the requirements for rotavirus interactions with these integrins. It will also be determined whether expression of these integrins on cells from the intestine, kidney, pancreas and immune system is a requirement for the cells to be infected with rotavirus. Previously, we have shown that rotavirus infection may be linked with progression of at-risk children towards development of type I diabetes, a pancreatic autoimmune disease. This means that understanding how the virus interacts with pancreatic and immune cells is of particular importance. The parts of the virus particle which bind to the integrins will be identified, and these will be produced and tested for their ability to block rotavirus infection in cells and in mice. It is likely that rotavirus binds to integrins by a somewhat different mechanism to that used by other viruses and cellular components. If this is so, then in future it should be possible to design drugs which block virus infection without interfering with the normal function of integrins. This work will also provide data useful for design of rotavirus vaccines, and for improved understanding of the disease process.Read moreRead less
RV3 Rotavirus Vaccine: A Human Neonatal Rotavirus Vaccine For The Asia-Pacific Region
Funder
National Health and Medical Research Council
Funding Amount
$2,264,330.00
Summary
Rotavirus infection is the leading cause of severe dehydrating gastroenteritis responsible for ~600,000 deaths per year in children <5 years of age worldwide. In this proposal we outline plans for the development of a human neonatal rotavirus vaccine in Indonesia. The goal is a safe and effective rotavirus vaccine affordable for children within the Asia-Pacific region and worldwide.
Roles Of Virus-integrin Interactions And Rotavirus Modulation Of Host Cell Responses In Viral Pathogenesis
Funder
National Health and Medical Research Council
Funding Amount
$474,000.00
Summary
Rotaviruses are the main cause of severe gastroenteritis in children, and cause 1 in 27 Australian children under the age of 5 years to spend time in hospital. There is currently no rotavirus vaccine available. We aim to discover how rotavirus interacts with host cells. This information is necessary to formulate a safe and effective vaccine, or a therapeutic agent that can block virus growth in host cells. Previously, we showed that rotavirus attaches to cells and enters them using several membe ....Rotaviruses are the main cause of severe gastroenteritis in children, and cause 1 in 27 Australian children under the age of 5 years to spend time in hospital. There is currently no rotavirus vaccine available. We aim to discover how rotavirus interacts with host cells. This information is necessary to formulate a safe and effective vaccine, or a therapeutic agent that can block virus growth in host cells. Previously, we showed that rotavirus attaches to cells and enters them using several members of the integrin protein family that are present on the surface of the cells. Integrins are critical for cell adhesion, survival and communication. In this project, we will identify how rotavirus usage of integrins modulates cell functions. This will help us understand how rotavirus causes disease, how virus spreads in the body and how the immune response defends us from rotavirus. Rotavirus binds integrins using particular stretches of protein sequence that we have shown are also present in other human viral pathogens that cause hepatitis, AIDS and measles. We will determine if these other viruses also recognize integrins.Read moreRead less