Flaviviruses are the agents of many mosquito-transmitted infections such as encephalitis and dengue. Hepatitis C virus is a member of the same virus family. Using Australian flavivirus Kunjin as a model and advanced techniques in molecular biology, biochemistry and electron micriscopy, the research at SASVRC has established international leadership in the area of flavivirus RNA replication and ultrastructure of virus-infected cells. The objectives of this application are to advance further our u ....Flaviviruses are the agents of many mosquito-transmitted infections such as encephalitis and dengue. Hepatitis C virus is a member of the same virus family. Using Australian flavivirus Kunjin as a model and advanced techniques in molecular biology, biochemistry and electron micriscopy, the research at SASVRC has established international leadership in the area of flavivirus RNA replication and ultrastructure of virus-infected cells. The objectives of this application are to advance further our understanding of how the flavivirus RNA replication complex synthesizes RNA and how this RNA is specifically packaged to produce infectious virus. To achieve these goals we will employ state-of-the-art molecular biology techniques based on manipulations with infectious complementary DNA copy of Kunjin virus RNA. The intimate understanding of these mechanisms in flavivirus replication should facilitate the design of efficient antiviral drugs by specifically targeting unique events in RNA replication and-or packaging. This may assist in the development of antiviral drugs for treatment of infections caused by other higly pathogenic flaviviruses in Australia, such as dengue, Japanese encephalitis and Murray Valley encephalitis, and in the rest of the wirld such as New York strain of West Nile virus as well as the related heptitis C virus. Understanding the mechanisms of Kunjin virus replication and assembly will also aid in the further development of this virus as a safe vaccine vector against other viruses, e.g. HIV, and diseases such as cancer.Read moreRead less
Molecular Analyses Of Flavivirus RNA Replication, Encapsidation, And Complementation
Funder
National Health and Medical Research Council
Funding Amount
$602,545.00
Summary
Flaviviruses are the agents of many mosquito-transmitted infections such as encephalitis and dengue. Hepatitis C virus is a member of the same virus family. Using Australian flavivirus Kunjin as a model and advanced techniques in molecular biology, biochemistry and electron micriscopy, the Flavivirus Research Unit at SASVRC has established itself as an international leader in the area of flavivirus RNA replication and ultrastructure of virus-infected cells. The objectives of this application are ....Flaviviruses are the agents of many mosquito-transmitted infections such as encephalitis and dengue. Hepatitis C virus is a member of the same virus family. Using Australian flavivirus Kunjin as a model and advanced techniques in molecular biology, biochemistry and electron micriscopy, the Flavivirus Research Unit at SASVRC has established itself as an international leader in the area of flavivirus RNA replication and ultrastructure of virus-infected cells. The objectives of this application are to advance further our understanding of how the flavivirus RNA replication complex is assembled, how it synthesizes RNA and how this RNA is specifically packaged to produce infectious virus. To achieve these goals we will employ state-of-the-art molecular biology techniques based on manipulations with infectious complementary DNA copy of Kunjin virus RNA. The intimate understanding of these mechanisms in flavivirus replication should facilitate the design of efficient antiviral drugs by specifically targeting unique events in RNA replication and-or packaging. This may assist in the development of antiviral drugs for treatment of infections caused by other higly pathogenic flaviviruses in Australia, such as dengue, Japanese encephalitis and Murray Valley encephalitis, as well as of the related heptitis C virus.Read moreRead less
Coordinated Cleavages In The Flavivirus Structural Polyprotein: Role In Virus Assembly And Host-pathogen Interaction
Funder
National Health and Medical Research Council
Funding Amount
$285,000.00
Summary
Flaviviruses are important human pathogens responsible for epidemics of hemorrhagic fever or encephalitis, world-wide. This project aims to investigate unique aspects in the biology of the flaviviruses with wider cell biological and immunological implications. First, we propose to test a mechanism important for the efficient assembly of virus particles. An understanding of this stage of the virus life-cycle will benefit research applying recombinant DNA technology in order to produce replication ....Flaviviruses are important human pathogens responsible for epidemics of hemorrhagic fever or encephalitis, world-wide. This project aims to investigate unique aspects in the biology of the flaviviruses with wider cell biological and immunological implications. First, we propose to test a mechanism important for the efficient assembly of virus particles. An understanding of this stage of the virus life-cycle will benefit research applying recombinant DNA technology in order to produce replication-incompetent viruses for use in vaccination and gene delivery. Second, we have recently discovered a mechanism for immune-modulation, so far unique to the flaviviruses, which interferes with the immune response important in the destruction of virus-infected cells. This project aims to identify the viral gene products responsible for this phenomenon.Read moreRead less
Flavivirus Replication - Biogenesis, Ultrastructure And Roles Of Induced Membranes
Funder
National Health and Medical Research Council
Funding Amount
$334,880.00
Summary
Flaviviruses are the agents of many mosquito-transmitted infections such as encephalitis and dengue, and hepatitis C virus is a member of the same virus family. During virus multiplication in cells, new membrane structures are induced and these represent regions where the replication events occur. Using Kunjin virus, an agent of Australian encephalitis, as a model, and advanced techniques in biochemistry and electron microscopy, we have previously identified these membranes as the site of synthe ....Flaviviruses are the agents of many mosquito-transmitted infections such as encephalitis and dengue, and hepatitis C virus is a member of the same virus family. During virus multiplication in cells, new membrane structures are induced and these represent regions where the replication events occur. Using Kunjin virus, an agent of Australian encephalitis, as a model, and advanced techniques in biochemistry and electron microscopy, we have previously identified these membranes as the site of synthesis of the viral RNA or genetic material, and the viral proteins involved. These comprise the viral replication complex. The research will define the origin of these membranes, and how the components of the associated replication complex are assembled. Assembly of the virus particles in cells is also being analysed using similar technology. Hepatitis C virus cannot be reliably grown at present for research purposes in cultured cells, and we will attempt to develop a helper system to overcome the problem. An understanding of these processes, and how the viral RNA is copied into progeny RNA for new virus particles, may assist in the development of antiviral drugs for treatment of slow or persistent virus infections such as hepatitis C.Read moreRead less
The Role Of Subgenomic Non-coding Viral RNA In Flavivirus Pathogenicity
Funder
National Health and Medical Research Council
Funding Amount
$555,325.00
Summary
Flaviviruses are transmitted by insects and pose a serious health threat to the Australian population. They can cause fever syndromes, encephalitis and death. We aim at better understanding of how these viruses cause disease. We are particularly interested in elucidating the role of small non-coding nucleic acid produced by flaviviruses in the viral pathogenicity. Ultimately, this deeper understanding should lead to the development of effective vaccines and antiviral therapies.
Structure, Function And Cellular Trafficking Of The Flavivirus NS1 Protein
Funder
National Health and Medical Research Council
Funding Amount
$496,500.00
Summary
Flaviviruses are spread mainly by mosquitoes or ticks and include globally important pathogens such as yellow fever, dengue, Japanese encephalitis and West Nile. This proposal seeks to elucidate the precise function of a component of the virus ( the NS1 protein) essential for its infection cycle. We will analyse the structure and function of this protein and its role in viral disease. A complete understanding of the replication cycle of these viruses will shed further light on how they have evol ....Flaviviruses are spread mainly by mosquitoes or ticks and include globally important pathogens such as yellow fever, dengue, Japanese encephalitis and West Nile. This proposal seeks to elucidate the precise function of a component of the virus ( the NS1 protein) essential for its infection cycle. We will analyse the structure and function of this protein and its role in viral disease. A complete understanding of the replication cycle of these viruses will shed further light on how they have evolved to replicate in animal cells and provide valuable information for the design of safe, new generation antiviral drugs and vaccines.Read moreRead less
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