Cellular Microenvironments Facilitating The Replication And Propagation Of Flaviviruses
Funder
National Health and Medical Research Council
Funding Amount
$505,279.00
Summary
Flaviviruses are the agents of many mosquito-transmitted infections and many deaths globally each year. The emerging virus West Nile virus (strain New York) is a member of this virus family and shares 99% amino acid homology with the endemic Australian virus Kunjin virus. During virus growth in cells, cellular membrane structures are induced or rearranged by these viruses for their own purpose. That being the production of more virus particles for reinfection of other cells. Using Kunjin virus a ....Flaviviruses are the agents of many mosquito-transmitted infections and many deaths globally each year. The emerging virus West Nile virus (strain New York) is a member of this virus family and shares 99% amino acid homology with the endemic Australian virus Kunjin virus. During virus growth in cells, cellular membrane structures are induced or rearranged by these viruses for their own purpose. That being the production of more virus particles for reinfection of other cells. Using Kunjin virus as a model, and advanced techniques in biochemistry and electron microscopy, we have identified for the first time these membrane structures as the apparent sites of replication of the viral RNA or genetic material, and of the viral proteins involved. We have also observed how new virus particles are able to get out of infected cells and shown how some drugs can prevent this occurring thus limiting their transmission. This research will focus on how the membrane structures are formed in infected cells. The research will determine what cellular components are required by the virus to help it propagate. In particular specific cellular proteins and membrane components that are captured by the virus and moved to different sites in the infected cells. These apparent requirements could possibly lead us to a greater understanding of the complex interactions that occur between the invading virus and the host cells. We aim to directly visualize the process of infection within living cells using new and innovative microscopic techniques. Another of our objectives is to determine the effects of infection on normal cells. The question being whether flavivirus infection disrupts normalcell fuctions like secretion etc. An understanding of these processes, and how the viral RNA is copied into new RNA for more virus particles, will assist in the development of antiviral drugs for treatment of this pathogenic group of viruses.Read moreRead less
Impact Of HIV Infection And Treatment With Highly Active Retroviral Therapy On Reverse Cholesterol Transport
Funder
National Health and Medical Research Council
Funding Amount
$339,375.00
Summary
HIV has been found to be associated with increased risk of cardiovascular diseases. The introduction of new treatment for HIV resulted in a dramatic improvement in morbidity and mortality of HIV-infected patients, but paradoxically cardiovascular complications became more frequent and severe. It is not currently clear whether increased cardiovascular risk is due to long lasting HIV or due to the impact of therapy. In both cases a major complication of HIV and-or therapy is rapid development of a ....HIV has been found to be associated with increased risk of cardiovascular diseases. The introduction of new treatment for HIV resulted in a dramatic improvement in morbidity and mortality of HIV-infected patients, but paradoxically cardiovascular complications became more frequent and severe. It is not currently clear whether increased cardiovascular risk is due to long lasting HIV or due to the impact of therapy. In both cases a major complication of HIV and-or therapy is rapid development of atherosclerosis. Atherosclerosis is the cause of more than half of heart diseases, which is a leading cause of death in Western societies. Atherosclerosis develops when cholesterol is deposited within artery walls, causing the formation of a fatty plaque and restricting blood flow. The mechanism behind the effect of HIV and its treatment on development of atherosclerosis is unknown. This project is designed to investigate how and why HIV infection and its treatment results in this increased risk of cardiovascular disease.Read moreRead less
What happens when viruses infect cells? How do they control the cells they infect? How do the make the cells do the things the virus wants? These are the questions that we aim to address within this research proposal. Primarily we hope to identify how viruses are able to replicate in cells and avoid immune detection. We believe these processes are related.