SERPINB2 IS AN INDUCIBLE HOST FACTOR INVOLVED IN ENHANCING HIV-1 TRANSCRIPTION AND REPLICATION
Funder
National Health and Medical Research Council
Funding Amount
$496,446.00
Summary
SerpinB2 is one of the most abundant proteins made at sites of inflammation. We have shown that HIV-1 infection also induces SerpinB2 and that SerpinB2 then helps the virus to replicate. In this grant we seek to understand how the virus causes this protein to be made and how this protein then increases virus replication. In the human population there are different forms of SerpinB2 and this grant seeks to determine whether these different forms affect HIV-1 replications differently. It may for i ....SerpinB2 is one of the most abundant proteins made at sites of inflammation. We have shown that HIV-1 infection also induces SerpinB2 and that SerpinB2 then helps the virus to replicate. In this grant we seek to understand how the virus causes this protein to be made and how this protein then increases virus replication. In the human population there are different forms of SerpinB2 and this grant seeks to determine whether these different forms affect HIV-1 replications differently. It may for instance be possible that an individual who has a certain form of SerpinB2 may be less susceptable to AIDS following HIV-1 infection.Read moreRead less
The Dengue Virus Glycoprotein NS1 Binds Cholesterol And Mediates Cellular Activation
Funder
National Health and Medical Research Council
Funding Amount
$632,029.00
Summary
Cholesterol has been shown to play a vital role in the life cycle of many viruses. This project will investigate the basis of dengue virus interaction with this important host molecule and along with investigations of how dengue is able to stimulate host cells, will provide new insights into the way these viruses cause severe disease. Findings from this study will also aid in the development of new drug strategies for dengue and related viruses such as West Nile virus.
The Impact Of HIV Integration Sites On Eliminating HIV Latency
Funder
National Health and Medical Research Council
Funding Amount
$778,313.00
Summary
Current antiviral therapy for HIV controls virus production and allows recovery but does not eliminate the silent infection that prevents complete virus elimination and cure. We will examine two ways that HIV can silently infect T cells for differences in the sites at which the HIV DNA inserts into the genome. We will examine the way in which these differences at the genomic level may limit the ability to activate and eliminate persistent infection in memory T cells.
Identification Of Host Factors That Restrict Influenza Virus Replication In Macrophages
Funder
National Health and Medical Research Council
Funding Amount
$566,446.00
Summary
Influenza virus infects different cells in the airways, including immune cells (macrophages) and non-immune cells (epithelial cells). Epithelial cell infection results in virus amplification and release whereas macrophage infection leads to virus destruction. This project will identify cellular factors expressed by macrophages that block virus amplification and release. Identification of novel antiviral factors is an important step towards developing strategies to reduce influenza disease.
Pathogenesis Of Persistent Human Virus Infections Of Global Significance
Funder
National Health and Medical Research Council
Funding Amount
$6,571,328.00
Summary
The study will investigate why humans cannot eradicate particular viruses (HIV-AIDS, cytomegalovirus and herpes simplex virus), the long term effects of these viruses and ways to improve control. Current treatments can only partly suppress the levels of these viruses, because they persist in certain parts of the body called reservoirs, only to resurge later causing disease. Thus, the overall aim of the research program is to discover the mechanisms by which these viruses are able to successfully ....The study will investigate why humans cannot eradicate particular viruses (HIV-AIDS, cytomegalovirus and herpes simplex virus), the long term effects of these viruses and ways to improve control. Current treatments can only partly suppress the levels of these viruses, because they persist in certain parts of the body called reservoirs, only to resurge later causing disease. Thus, the overall aim of the research program is to discover the mechanisms by which these viruses are able to successfully persist within reservoirs in the human body. The research program brings together a group of 6 leading scientists and clinicians located at 3 sites in 2 Australian cities. The team is comprised of experts in the study of HIV-AIDS, cytomegalovirus and herpes simplex virus who will combine their knowledge and expertise to speed up the process of research on these viruses that are of major health importance. Studies will also utilise a number of cutting edge technologies that now make it possible to much more rapidly and precisely determine how viruses cause disease. Advances in our understanding of how viruses persist may form the basis for treatments aimed at controlling persistent infections and the serious diseases caused by these viruses.Read moreRead less
Novel Insights Into The Pathobiology Of Alphavirus Infections
Funder
National Health and Medical Research Council
Funding Amount
$583,477.00
Summary
Ross River virus and chikungunya virus cause muscle and joint pain that can persist for a long time. This project looks at factors in the human host that affect the disease severity, with the aim of finding new treatments.
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.
Human immunodeficiency virus type 1 (HIV-1) causes AIDS and, to date, has infected approximately 20 thousand people in Australia and more than 40 million worldwide. People infected with HIV-1 first experience a period of 5-7 years where they remain healthy, ofter assisted by the use of anti-HIV-1 drugs, and this period is referred to as the asymptomatic period. After this period, infected individuals become sick due to their immune system being destroyed, and this is referred to as AIDS. Researc ....Human immunodeficiency virus type 1 (HIV-1) causes AIDS and, to date, has infected approximately 20 thousand people in Australia and more than 40 million worldwide. People infected with HIV-1 first experience a period of 5-7 years where they remain healthy, ofter assisted by the use of anti-HIV-1 drugs, and this period is referred to as the asymptomatic period. After this period, infected individuals become sick due to their immune system being destroyed, and this is referred to as AIDS. Research into how HIV-1 causes AIDS has shown us that the virus changes over time to make itself better able to kill cells of the immune system, by at least 2 mechanisms. The first mechanism, which is the best characterised one, is where the virus changes the way it infects cells, whereby it can infect many more cells in the body by taking advantage of an alternate receptor molecule on the cell called CXCR4. This molecule is very widely expressed on immune cells, and thus the virus can now infect and kill many more cells. However, in about 50% of infected people who eventually get AIDS, the virus does not change this way. The virus instead uses it's original receptor to infect cells, called CCR5. Our preliminary studies, as well as other published reports, suggest that the virus changes itself another way to make it kill immune cells better, without using CXCR4. However, the mechanism by which HIV-1 does this is poorly understood. This proposal aims to better understand this mechanism. We expect to find that, in this group of patients, the Env proteins on the virus change to be able to bind CCR5 more tightly, and thus be able to use fewer molecules of CCR5 to infect cells. We believe that these forms of the virus are now better able to kill immune cells, leading to AIDS. This study will contribute to a greater understanding of how HIV-1 causes AIDS, which is necessary for the development of new drugs to treat HIV-1 infection.Read moreRead less
Understanding The Role Of Host Arih2 In Defence Against Viral Infection And Disease Pathogenesis
Funder
National Health and Medical Research Council
Funding Amount
$537,737.00
Summary
A set of proteins, called E3 ligases, modulate many aspects of immunity. Arih 2 is a novel E3 ligase that limits immune cell activation to maintain the immune system in a quiescent state. The details of how Arih2 functions and its role in immunity to chronic overwhelming infection are the focus of this study. The insights gained from these studies have important implications for our understanding of how immune responses can be promoted during infection or halted in autoimmunity.