Successful HIV remission and cure, where patients can live normally without daily drug therapy and risk of transmitting infectious virus, will critically depend on understanding the mechanisms that control the expression of viral messenger RNA and proteins. This project further explores the mechanisms controling poorly understood steps in the proecssing of viral mRNA that are required for HIV protein produciton, and identifies new targets and strategies to drive HIV into permanent remission.
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.
HIV is a rapidly evolving virus, and within an infected individual it continually acquires new mutations and joins together mutations by recombination. We have developed a novel system for studying recombination, and find that different individuals have different recombination rates, which may contribute to why some individuals survive longer. This project aims to identify the mechanisms responsible for differing recombination rates and how we can alter these to improve patient outcome.
Topical microbicides are urgently required to protect women from the sexual transmission of HIV. Lactic acid is produced by bacteria that are normally present in the healthy female vaginal tract and is more potent in the inactivation of HIV compared to low pH alone. This study seeks to determine how lactic acid inactivates HIV and to undertake laboratory studies to determine its suitability for development as a topical microbicide to prevent HIV transmission.
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.
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.
The primary aim of this grants to determine how HIV spreads through our immune system. The above knowledge will determine key Achille’s Heel moments in the HIV life cycle and thus lead to better therapeutic HIV treatments/prevention.
Characterize The Post-entry Events Of HIV Infection
Funder
National Health and Medical Research Council
Funding Amount
$605,190.00
Summary
For HIV to successful infect a target cell, it must properly remove the outer layers of its protective gears (outer viral protein coats) to allow the viral genetic materials to be replicate (duplicate and multiplied) for the generation of their ‘offspring viruses’. This process is known as viral uncoating, and it is arguably one of the least understood areas of HIV. In this proposal, we will use a number of complementary state-of-the-arts research tools to characterize the HIV uncoating process.
HIV infection is a dynamic process, in which the host immune response tries to control viral growth and keep up with the rapid evolution of the virus. This project assembles an interdisciplinary team of mathematicians and biologists to use a modelling approach to understand the dynamics of viral infection, viral evolution, and immune control in the infected individual. The insights gained from this project will help in the development of new drug and vaccination strategies.
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.