The Role Of Paramyxovirus P Protein Subcellular Trafficking In Virus Pathogenicity And Antagonism Of Host Interferon Responses
Funder
National Health and Medical Research Council
Funding Amount
$78,491.00
Summary
Emerging zoonotic viruses pose a major health threat worldwide, highlighted by recent outbreaks of viruses such as Nipah and Hendra via interspecies invasion to infect humans. A major barrier to interspecies infection is the innate immune response, which viruses must evolve to combat before successful infection can occur. We aim to examine in detail the mechanisms underlying immune evasion of such viruses, with the ultimate goal of discovering novel targets for therapeutics to viral infection.
We will construct different genetically engineered viruses, which infect cells in the respiratory tract, to deliver genes encoding proteins from human immunodeficiency virus (the AIDS virus). These engineered viruses can be expected to generate an active immune response in mucosal tissues, including the vaginal and rectal tracts. As these are the major routes for transmission of the AIDS virus, these new vaccines are expected to reduce transmission of the AIDS virus.
Molecular Characterisation Of Host Cell Targets Of Human Pathogenic Viruses And Evaluating Their Potential As Novel Therapeutic Targets.
Funder
National Health and Medical Research Council
Funding Amount
$307,946.00
Summary
There are currently no therapeutics to treat victims of Hendra, Nipah or Rabies virus infections, which account for > 50,000 deaths/yr worldwide. Through not fully understood mechanisms, these viruses affect the functions of specific cellular proteins in order to inhibit the host immune system, a process essential to their pathogenicity. We aim to characterise the mechanisms underlying viral inhibition of host immunity and evaluate their potential as novel targets to develop urgently needed t ....There are currently no therapeutics to treat victims of Hendra, Nipah or Rabies virus infections, which account for > 50,000 deaths/yr worldwide. Through not fully understood mechanisms, these viruses affect the functions of specific cellular proteins in order to inhibit the host immune system, a process essential to their pathogenicity. We aim to characterise the mechanisms underlying viral inhibition of host immunity and evaluate their potential as novel targets to develop urgently needed therapeutics against these deadly pathogens.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