HIV Assembly, Transport, Egress And Transfer From Infected Dendritic Cells
Funder
National Health and Medical Research Council
Funding Amount
$511,629.00
Summary
HIV-AIDS is the fourth leading killing disease worldwide, with the disease burden shifting towards women. Study of the HIV life cycle in cells known to be targetted during HIV transmission is key towards designing additional preventative measures in the form of topical gels known as microbicides. Mapping of the basic pathways of viral transport within such cells, will aid further drug discovery and-or appropriateness of use of existing drugs in microbicide formulations.
Does HIV Function As A Lipid-raft During Infection?
Funder
National Health and Medical Research Council
Funding Amount
$607,289.00
Summary
The exterior surface of HIV has a layer of lipids (a type of fat), which represents approximately 1-3 of HIV by weight. This layer of lipids may serve as a mechanistic trigger, which enables viral components to be systemically released or dispatched from the main structure post-entry to establish successful infection. Completion of this project will define the role of lipids in this process. This new knowledge will be vital to identify new targets to deter the HIV infection process.
The HIV-1 Spacer Peptide P1: A Novel Anti-retroviral Target
Funder
National Health and Medical Research Council
Funding Amount
$384,000.00
Summary
Human immunodeficiency virus type 1 (HIV-1) is the virus that causes AIDS. The treatment that is in current use, called highly active anti-retroviral therapy (HAART), has significantly delayed the onset of AIDS in HIV-1 infected patients. This therapeutic regimen requires the action of three or more drugs to generate a potency that is sufficient to suppress the virus and restrict outgrowth of resistant mutants. However, even on HAART the virus continues to replicate at a low level, and the threa ....Human immunodeficiency virus type 1 (HIV-1) is the virus that causes AIDS. The treatment that is in current use, called highly active anti-retroviral therapy (HAART), has significantly delayed the onset of AIDS in HIV-1 infected patients. This therapeutic regimen requires the action of three or more drugs to generate a potency that is sufficient to suppress the virus and restrict outgrowth of resistant mutants. However, even on HAART the virus continues to replicate at a low level, and the threat of the development of resistant mutations is ever present. Consequently, additional drug targets are required to continue the successful treatment of HIV-1 infected patients. This research is focused on a large polyprotein produced by HIV called Gag. One end of Gag contains a smaller protein called P1 that is crucial for the ability of HIV to reproduce itself. Small changes to the genetic makeup of P1 (one or two amino acids) lead to a defective virus that cannot replicate. The apparent integral role of P1 in viral replication makes it an excellent target for anti-retroviral therapy. With this project we will further our understanding of P1's role in HIV replication and look at ways we target P1 for the development of effective anti-viral agents.Read moreRead less
Human immunodeficiency virus type 1 (HIV-1) is the causative agent of AIDS. Recent advances with combination antiretroviral therapy have prolonged the survival time of HIV-1 infected patients, and provideed two important hints for a strategy to effectively treat this disease. First, administration of a combination of antiretroviral agents that target different stages of the viruses life cycle improves the clinical status of HIV-1 infected patients; and second, the formation of viral particles du ....Human immunodeficiency virus type 1 (HIV-1) is the causative agent of AIDS. Recent advances with combination antiretroviral therapy have prolonged the survival time of HIV-1 infected patients, and provideed two important hints for a strategy to effectively treat this disease. First, administration of a combination of antiretroviral agents that target different stages of the viruses life cycle improves the clinical status of HIV-1 infected patients; and second, the formation of viral particles during the HIV-1 replication cycle is an effective target for antiretroviral treatment, as demonstrated by the potency of drugs called protease inhibitors. A virus such as HIV is composed of viral proteins as well as genetic material called RNA. Two strands of viral RNA come together during the formation of HIV-1 in a process callered dimerization. It may be possible to interfere with RNA dimerization thus inhibiting HIV replication. This would provide a new target for HIV therapy. In order to do this, the process of RNA dimerization needs to be understood.The focus of this project is to define the mechanism of HIV-1 RNA dimerization, and to identify factors that are critical for virion RNA dimerization. Understanding the mechanism of virion RNA dimerization is likely to provide novel therapeutic target for the development of effective antiviral agents.Read moreRead less
Regulation Of Endosome Function By The AAA-ATPase Vps4
Funder
National Health and Medical Research Council
Funding Amount
$220,500.00
Summary
Cells respond to many signals from the environment. Some signals tell cells to grow and divide and other signals tell cells to rest. These signals are usually in balance in healthy cells. To prevent cells from growing and dividing in an uncontrolled manner and forming a cancer, there are mechanisms to turn off signals for growth. One mechanism is to destroy the proteins responsible for growth signalling. This involves flipping (by a process called multivesicular body, or MVB, sorting) the signal ....Cells respond to many signals from the environment. Some signals tell cells to grow and divide and other signals tell cells to rest. These signals are usually in balance in healthy cells. To prevent cells from growing and dividing in an uncontrolled manner and forming a cancer, there are mechanisms to turn off signals for growth. One mechanism is to destroy the proteins responsible for growth signalling. This involves flipping (by a process called multivesicular body, or MVB, sorting) the signalling protein from one side of the membrane where signalling occurs to the other side where signalling cannot occur and where the signalling protein can be degraded. Interestingly, it has recently been discovered that some viruses (including the AIDS virus) use the same MVB sorting mechanisms to escape from infected cells. Instead of undergoing MVB sorting into an internal compartment and getting degraded, however, the virus is able to use the same mechanism to flip out of the cell. How MVB sorting occurs is not known, but the mechanism has been conserved through evolution and even microbes like yeast can perform MVB sorting of proteins. We are investigating a component of the MVB sorting mechanism known as Vps4 which is present in both human cells and in yeast cells. Since the human Vps4 and yeast Vps4 seem to function in the same way, and since powerful molecular genetic approaches can be used in yeast to elucidate how proteins function (some of which are not possible with human cells), we are using yeast to investigate Vps4 function. Once we understand how the yeast Vps4 works, we will be able to test if human Vps4 works the same way. Understanding the MVB sorting mechanism will give us information on how cells prevent uncontrolled growth and division and may also help us find ways of preventing AIDS infection.Read moreRead less
Structural Analysis Of Poxvirus Immature Particles And Spheroids
Funder
National Health and Medical Research Council
Funding Amount
$387,489.00
Summary
Despite the eradication of smallpox by vaccination, poxviruses remain a threat to public health because of bioterrorist scares from kept variola stocks and because of the possible emergence of other poxvirus pathogens from the extensive animal reservoir. The structural analysis of the assembly of poxvirus will not only improve our knowledge of fundamental processes, highly conserved in DNA viruses, but could also provide valuable targets for the rational design of antiviral drugs.
The Role Of HIV Infection Of Astrocytes In The Development Of HIV Associated Dementia
Funder
National Health and Medical Research Council
Funding Amount
$144,250.00
Summary
Dementia is an extremely common problem in the late stages of Human Immunodeficiency Virus (HIV) infection. HIV-associated dementia is the most common cause of dementia in people under 40 years of age. Despite the development of very good drugs to attack the virus, HIV-associaed dementia continues to be a major clinical problem. We are looking at the reasons why some people infected with HIV become demented and others do not. We are also looking at how best to prevent the development of dementia ....Dementia is an extremely common problem in the late stages of Human Immunodeficiency Virus (HIV) infection. HIV-associated dementia is the most common cause of dementia in people under 40 years of age. Despite the development of very good drugs to attack the virus, HIV-associaed dementia continues to be a major clinical problem. We are looking at the reasons why some people infected with HIV become demented and others do not. We are also looking at how best to prevent the development of dementia. We believe that astrocytes (an important brain cell that supports neurons) play a very important role in the development of HIV-associated dementia. With an improved understanding of the steps leading to dementia we can better plan treatments to prevent the development of this devastating complication of HIV-AIDS.Read moreRead less
Macfarlane Adaptive Changes In HIV-1 Subtype C Envelope Glycoproteins Contributing To Pathogenicity.
Funder
National Health and Medical Research Council
Funding Amount
$310,787.00
Summary
HIV exists as multiple subtypes. The most commonly studied is type B (B-HIV). B-HIV is common in developed countries, but accounts for only a small fraction of HIV infections worldwide. Type C HIV (C-HIV) in Africa and Asia accounts for the majority of infections worldwide, yet very little is known about how C-HIV causes AIDS. We aim to understand how C-HIV causes AIDS. This is critical for development of drugs and vaccines specifically designed for those who are most urgently need.