The Role Of Vif In Enhancing HIV Replication And Effecting The Integrity Of The Replication Complexes Of HIV
Funder
National Health and Medical Research Council
Funding Amount
$260,200.00
Summary
HIV-AIDS is still one of the leading causes of infectious human fatality worldwide. The genome of HIV encodes six viral accessory proteins that are necessary for viral replication and infection. One of these genes, viral infectivity factor (vif), is essential for production of infectious virus. Exactly how this viral protein works within the cell is not clear at present. Current literature suggests that Vif acts in some way to enhance reverse transcription, one of the early stages of the viral l ....HIV-AIDS is still one of the leading causes of infectious human fatality worldwide. The genome of HIV encodes six viral accessory proteins that are necessary for viral replication and infection. One of these genes, viral infectivity factor (vif), is essential for production of infectious virus. Exactly how this viral protein works within the cell is not clear at present. Current literature suggests that Vif acts in some way to enhance reverse transcription, one of the early stages of the viral life cycle. We aim to investigate the action of Vif in stabilizing early HIV reverse transcription complexes to understand how it acts to enhance HIV replication and viral infection. The early stages of HIV replication are critical for establishing infection and hence ideal targets for therapeutic intervention. This research will help understand how Vif works in a cell and affects the infectivity of HIV viral particles and may be suggestive of potential targets for development of anti-viral drugs.Read moreRead less
Defining The Requirement For The Inhibition Of Bak To The Pathogenesis Of Cytomegalovirus Infection
Funder
National Health and Medical Research Council
Funding Amount
$592,661.00
Summary
Apoptosis, or programmed cell death is a powerful defence mechanism against viral infection. Thus, to replicate efficiently viruses have evolved means to inhibit apoptosis. The central aim of this work is to understand how cytomegalovirus prevents cell death protein during infection. The proposed studies will improve our understanding of the mechanisms that regulate viral replication and will contribute insights into the normal processes that control cell survival.
Viral disease is a major health hazard in the modern world. SV40 is a relatively simple virus which must enter mammalian cells in order to replicate. As it does so, it causes the infected cell to divide and hence triggers tumour formation in the host. This proposal is aimed at understanding how SV40 enters cells, and then passes to the nucleus where it replicates. Most viruses have hijacked existing pathways into cells. For example, some viruses have used the pathway by which cells take up nutri ....Viral disease is a major health hazard in the modern world. SV40 is a relatively simple virus which must enter mammalian cells in order to replicate. As it does so, it causes the infected cell to divide and hence triggers tumour formation in the host. This proposal is aimed at understanding how SV40 enters cells, and then passes to the nucleus where it replicates. Most viruses have hijacked existing pathways into cells. For example, some viruses have used the pathway by which cells take up nutrients from the external medium. However, we have shown that SV40 uses a completely novel pathway involving surface pits called caveolae. The subsequent steps in the pathway are unknown and have been difficult to study. We have discovered a number of agents which inhibit infection by SV40. In this proposal we will characterise the infectious entry pathway by investigating exactly where in the cell these agents work. We will then isolate the virus from within the cell and attempt to reconstitute part of the viral entry pathway in vitro. These studies will provide insights into the entry pathway of the virus which may lead to new therapeutic strategies to combat viral disease. In addition, study of this pathway, leading from the cell surface to the nucleus, may provide new avenues for drug delivery and-or gene targetting.Read moreRead less
Current combination antiviral therapy can't cure an HIV infection because long-lived T-cells carrying latent HIV DNA can rekindle the infection when drugs are removed. We will study elements in HIV genetic code that control expression of HIV proteins from latent HIV. A detailed molecular understanding of the structure and function of these HIV RNA elements and the viral and host cell factors that interact with them will expose new targets for therapy of latent HIV.
Hepatitis C Virus infects 3% of the world's population causing recurring liver disease, cirrhosis and hepatocellular carcinoma. To infect a liver cell, the viral glycoproteins attach to cell surface molecules wher they are activated to mediate merger of the viral and cellular membranes. This project grant will explore how the viral glycopropteins become activated and obtain essential structural information on the viral glycoproteins. These studies will help us to design antiviral agents.
The Role Of Cyp2e1, Alcohol And HCV In Modulation Of Hepatocyte Homeostasis HCV Replication And Resistance To Interferon
Funder
National Health and Medical Research Council
Funding Amount
$455,520.00
Summary
Liver disease caused by alcohol consumption and hepatitis C virus (HCV) infection are major national health problems. Liver disease caused by HCV is greatly accelerated by alcohol consumption, however, the connection between the biochemical events initiated by alcohol, HCV and inflammatory pathways resulting in liver disease are not well understood. Preliminary studies have identified a link between an important alcohol-metabolising enzyme, Cyp2e1, HCV replication, oxidative stress and a powerfu ....Liver disease caused by alcohol consumption and hepatitis C virus (HCV) infection are major national health problems. Liver disease caused by HCV is greatly accelerated by alcohol consumption, however, the connection between the biochemical events initiated by alcohol, HCV and inflammatory pathways resulting in liver disease are not well understood. Preliminary studies have identified a link between an important alcohol-metabolising enzyme, Cyp2e1, HCV replication, oxidative stress and a powerful mediator of liver injury called tumour necrosis factor alpha. Furthermore we have shown that alcohol metabolism by Cyp2e1 results in an increase in HCV replication and negatively impacts on the anti-viral action of interferon. The studies contained within this proposal aim to build on these exciting new insights by attempting to identify new mediators and mechanisms of liver disease as a consequence of Cyp2e1 expression, alcohol and HCV replication. We will also examine the molecular mechanisms by which alcohol potentiates HCV replication. These studies will assist in developing therapeutic strategies that will benefit alcohol- and HCV-related liver disease.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