HIV Phenotypes Important For The Establishment Of Persistent Reservoirs In The Central Nervous System And Which Impact Neurotropism And Neuropathogenesis
Funder
National Health and Medical Research Council
Funding Amount
$762,492.00
Summary
This grant will determine whether or not the CNS is a reservoir for HIV and identify the cellular targets of persistent infection and type of HIV-1 present.
Characterising The Genotypic And Phenotypic Properties Of The HIV-1 Viral Reservoir
Funder
National Health and Medical Research Council
Funding Amount
$316,819.00
Summary
Current drug treatments can not eradicate HIV from the body. This is because HIV can infect and establish a latent or “silent” infection in long-lived cells of the immune system that can re-emerge out of these cells when drug treatment is stopped. This project aims to find out how these cells become infected and what type of HIV is infecting them. The results from this study will help us better understand the latent infection and will help researchers design ways to eradicate HIV.
Envelope Glycoprotein Determinants Of HIV-1 Subtype C Tropism And Pathogenicity
Funder
National Health and Medical Research Council
Funding Amount
$657,745.00
Summary
HIV-1 subtype C is the most common subtype of HIV-w worldwide, yet we know comparatively little about how it causes disease in humans. This study will elucidate how HIV-1 subtype C evolves in patients to become more pathogenic over time.
Novel HIV-1 Glycoprotein Vaccines With Enhanced Presentation Of Broad Neutralization Epitopes
Funder
National Health and Medical Research Council
Funding Amount
$743,682.00
Summary
A prophylactic vaccine represents the best strategy for blocking HIV-1 transmission but one is not yet available. Current antiviral vaccines rely on neutralizing antibodies (NAbs) that block infection, however, current HIV-1 vaccine formulations do not induce broadly reactive NAbs (bNAbs). We have discovered a novel HIV-1 glycoprotein vaccination candidate with enhanced presentation of bNAb epitopes. We propose to determine if this vaccine induces effective bNAbs in experimental animals.
Envelope Glycoprotein Determinants Underlying Cytopathicity Of CCR5-restricted Human Immunodeficiency Virus Type 1
Funder
National Health and Medical Research Council
Funding Amount
$428,602.00
Summary
HIV weakens the immune system causing AIDS, but the mechanism by which HIV does this are poorly understood. This proposal aims to define these mechanisms. We expect that HIV evolves in infected people, becoming better able to infect and kill cells of the immune system, and that this results from specific genetic changes in the virus. This study will contribute to a greater understanding of how HIV causes AIDS, which is necessary for the development of new drugs to treat HIV infection.
Assembly Functions Of Respiratory Syncytial Virus Matrix Protein
Funder
National Health and Medical Research Council
Funding Amount
$239,250.00
Summary
Respiratory syncytial virus (RSV) is the single most important cause of lower respiratory infections (pneumonia and bronchiolitis) in young infants. In addition to the morbidity of RSV infection itself, it is well established that symptomatic RSV infection in infancy predisposes to asthma later in life. As all infants are infected by RSV at least once by age 2 yrs, this virus represents a major public health problem. Additionally, re-infection by RSV is increasingly being recognized as a cause o ....Respiratory syncytial virus (RSV) is the single most important cause of lower respiratory infections (pneumonia and bronchiolitis) in young infants. In addition to the morbidity of RSV infection itself, it is well established that symptomatic RSV infection in infancy predisposes to asthma later in life. As all infants are infected by RSV at least once by age 2 yrs, this virus represents a major public health problem. Additionally, re-infection by RSV is increasingly being recognized as a cause of severe lower respiratory disease in the elderly and in immunocompromised patients. The goal of this research is to understand better the mechanisms used by RSV to replicate itself in mammalian cells. Information from this work could be used to design novel antiviral drugs to treat RSV, and novel attenuating mutations that may assist in developing live RSV vaccines. The research focuses on a key viral protein, the matrix (M) protein, which is involved in many steps in virus replication. We aim to understand how M protein interacts with other components of the virus (specifically, envelope proteins) to orchestrate virus assembly. To coordinate assembly of new virus particles, M protein binds to portions of virus envelope glycoproteins and to RSV nucleocapsids (the internal machinery of the virus), bringing them together at the cell membrane. The protein-protein interactions which are responsible for these functions of RSV M protein will be determined.Read moreRead less
Studies On The Activation And Immunogenicity Of The HIV-1 Glycoproteins, Gp120-gp41
Funder
National Health and Medical Research Council
Funding Amount
$606,438.00
Summary
More than 34 million people were living with HIV-1 in 2011 with ~7,000 new infections still occurring daily. A prophylactic vaccine for HIV-1 is needed to stop its transmission, however, this goal is yet to be achieved. Our proposed studies will inform the design of prophylactic HIV-1 vaccines that act by making antibodies that neutralize the virus.
Structure And Function Of Hepatitis C Virus Glycoproteins
Funder
National Health and Medical Research Council
Funding Amount
$480,750.00
Summary
Hepatitis C Virus infects approximately 200 million people world-wide and is the major cause of liver transplantation in the Western world. At present there is no vaccine and interferon alpha is the only therapy available and has only limited success in clearing viral infection. HCV is distantly related to flaviviruses eg tick-borne encephaltitis virus and yellow fever virus. All viruses attach to target cells using receptors to initiate the infection process. In the case of HCV, the envelope gl ....Hepatitis C Virus infects approximately 200 million people world-wide and is the major cause of liver transplantation in the Western world. At present there is no vaccine and interferon alpha is the only therapy available and has only limited success in clearing viral infection. HCV is distantly related to flaviviruses eg tick-borne encephaltitis virus and yellow fever virus. All viruses attach to target cells using receptors to initiate the infection process. In the case of HCV, the envelope glycoproteins interact with as yet unknown receptors on the target cell surface resulting in the virus being internalized into endosomes. It is believed that the low pH environment of these endosomes triggers fusion of the viral and cellular membranes. After fusion the genome of the virus is released into target cells and begins the replication process. The actual events intitiating these processes are not understood for HCV but are believed to be mediated using two envelope glycoproteins. In this project we seek to gain a greater understanding of how viral fusion and entry occurs. We have new information regarding the localisation of the two envelope glycoproteins that will now enable us to carefully examine how viral fusion occurs. Using biochemical approaches, we will study their structure and function and examine how this relates to the well understood flavivirus mode of fusion and entry. We will test the functional consequences of altering the structure of the HCV envelope glycoproteins by developing in vitro assays of HCV fusion. Assays for HCV fusion are essential for future studies to identify viral receptors, examine the role of antibody in viral neutralization and can be used to test novel inhibitors of viral fusion and entry.Read moreRead less
Elucidating Unique Molecular Mechanisms Involved In HIV-1 Subtype C Pathogenicity
Funder
National Health and Medical Research Council
Funding Amount
$710,989.00
Summary
Most people infected with human immunodeficiency virus (HIV) have subtype C virus (C-HIV) and live in Southern Africa and Central Asia. These regions are where the HIV pandemic is at its worst. However, we know very little about C-HIV. We have evidence that C-HIV evolves differently compared to other HIV-1 subtypes, which impacts the way it leads to AIDS. This project aims to characterise these unique molecular mechanisms, which may lead to vaccines and drugs that are optimised for C-HIV.
Elucidating The Flexibility Of Coreceptor Engagement By HIV-1 Important For Macrophage Tropism And Escape From Entry Inhibitors
Funder
National Health and Medical Research Council
Funding Amount
$635,506.00
Summary
CCR5 antagonists are a new type of anti-HIV-1 drug that stops the virus from entering cells. We have evidence to suggest that the ability of CCR5 antagonists to function properly is linked to the ability of HIV-1 to infect a type of immune cell called macrophages. In this proposal, we will investigate precisely how HIV-1 enters macrophage cells, and then determine how this may influence the outcome of patients who are receiving these drugs as part of their clinical care.