Silent Mutations In The HIV-1 Reverse Transcriptase Selected During Antiretroviral Therapy
Funder
National Health and Medical Research Council
Funding Amount
$555,325.00
Summary
This project seeks to determine the role of silent mutations in the HIV reverse transcriptase that are selected during drug therapy in HIV infected individuals on HIV fitness, reverse transcriptase function and the emergence of drug resistance. This study will increase our understanding of the mechanisms by which the virus evades the effects of antiretrovirals and will provide a rationale for deciding on the best drug combinations for use in patients infected with specific HIV strains (clades).
Worldwide there are approximately 40 million people living with HIV-AIDS. An effective HIV vaccine does not exist at present. Therefore, current strategies to control the HIV pandemic include the use of life saving antiretroviral drugs. While the current drugs are successful in controlling infections, new and more effective agents are needed that inhibit HIV replication by distinct mechanisms due to the inevitable development of drug resistant strains of HIV. The HIV reverse transcriptase enzyme ....Worldwide there are approximately 40 million people living with HIV-AIDS. An effective HIV vaccine does not exist at present. Therefore, current strategies to control the HIV pandemic include the use of life saving antiretroviral drugs. While the current drugs are successful in controlling infections, new and more effective agents are needed that inhibit HIV replication by distinct mechanisms due to the inevitable development of drug resistant strains of HIV. The HIV reverse transcriptase enzyme is essential for HIV replication and has been a successful target for nucleoside reverse transcriptase inhibitors (NRTIs) and nonnucleoside reverse transcriptase inhibitors (NNRTIs). NNRTIs act in part by stabilizing the reverse transcriptase enzyme, thus blocking enzyme function. However, no drugs have been developed that can specifically prevent formation of the reverse transcriptase enzyme, which would result in the production of noninfectious viral particles. We propose that formation of the active reverse transcriptase enzyme, from a large polyprotein called Gag-Pol, proceeds through a homodimer intermediate, which represents an ideal target for blocking reverse transcriptase formation in HIV infected cells. This homodimer intermediate is an attractive target with greater potential for disruption with small molecule inhibitors compared to the mature reverse transcriptase enzyme as it is less stable than the reverse transcriptase found in viruses. This study will determine whether formation of the active RT enzyme is dependent on this intermediate. In addition, we will examine how the reverse transcriptase encoded on Gag-Pol regulates activation of the HIV protease, which is also critical for the formation of infectious virus particles. These studies will increase our understanding of how the virus produces infectious particles and will identify new approaches for targeting the HIV reverse transcriptase enzyme.Read moreRead less
I am a virologist carrying out research to determine the mechanisms underlying rotavirus cellular tropism and the pathogenesis of rotavirus disease. Rotavirus is the major cause of infantile gastroenteritis worldwide. I am combining the expertise of my group in rotavirus biology with the power of inter-disciplinary collaborations in the areas of sugar chemistry, cell biology, structural biology and diabetes to expand understanding in these areas. Novel treatments and improvements in rotavirus va ....I am a virologist carrying out research to determine the mechanisms underlying rotavirus cellular tropism and the pathogenesis of rotavirus disease. Rotavirus is the major cause of infantile gastroenteritis worldwide. I am combining the expertise of my group in rotavirus biology with the power of inter-disciplinary collaborations in the areas of sugar chemistry, cell biology, structural biology and diabetes to expand understanding in these areas. Novel treatments and improvements in rotavirus vaccines are the long term goal of our research.Read moreRead less
Resolving Human Immunodeficiency Virus (HIV) Transmission
Funder
National Health and Medical Research Council
Funding Amount
$745,213.00
Summary
To increase the breadth of HIV prevention strategies, it is imperative that we biologically understand how HIV enters our bodies. Through two unique clinical cohorts, we will determine why circumcision is protective and how a commonly acquired sexual transmitted infection (human papilloma virus) can increase HIV transmission.
The Human Immunodeficiency Virus (HIV) is a virus that infects and kills the cells of your immune system. This infection eventually leads to the Acquired Immune Deficiency Syndrome (AIDS). An important aspect in preventing infection is to study how HIV enters immune cells and how infection spreads. Our lab is researching drugs to block the entry of HIV in immune cells, which can hopefully be used together with existing anti-HIV drugs to slow down the spread of the virus and the onset of AIDS.
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.
Improved Health Outcomes For People Living With HIV
Funder
National Health and Medical Research Council
Funding Amount
$560,284.00
Summary
Despite the success of antiviral therapy for HIV infection, HIV cannot be cured and treatment is life long. In addition, there are complications in patients on long term antiviral therapy due to impaired immune recovery. This grant will identify strategies to eliminate HIV from latently infected cells that persist in patients on antiviral therapy as well as identify novel ways to improve the immune response to antiviral treatment for patients with HIV infection as well as patients co-infected wi ....Despite the success of antiviral therapy for HIV infection, HIV cannot be cured and treatment is life long. In addition, there are complications in patients on long term antiviral therapy due to impaired immune recovery. This grant will identify strategies to eliminate HIV from latently infected cells that persist in patients on antiviral therapy as well as identify novel ways to improve the immune response to antiviral treatment for patients with HIV infection as well as patients co-infected with hepatitis B virus (HBV)Read moreRead less
A Novel RNA Repressor Element Regulates HIV-1 Replication
Funder
National Health and Medical Research Council
Funding Amount
$341,453.00
Summary
HIV-1 causes acquired immunodeficiency syndrome, with up to 40 million infected people and 5 million infected annually. The spatio-temporal regulation of HIV-1 reverse transcription has recently been recognised as a possible new drug target. Our research has revealed a novel repressor of reverse transcripiton (RRT). The RRT plays a major role in regulating the spatio-temporal regulation of reverse transcripiton. Targetting the RRT function would be a novel means to combat HIV-1 infection.
Addressing The Major Challenges In HIV Vaccine And Cure Research
Funder
National Health and Medical Research Council
Funding Amount
$16,136,755.00
Summary
HIV remains one of the defining global health challenge of our times. 37 million people are living with HIV with 2 million new infections each year. Despite advances in management of HIV infection with antiretroviral therapy, there is still no cure, no effective vaccine, and several co-infections reduce life expectancy. This program assembles Australia’s leading HIV researchers to use innovative basic and translational science to tackle priority areas in controlling the HIV epidemic.
An RNA Element Negatively Regulates Initation HIV-1 Reverse Transcription And Inhibits Proviral Integration
Funder
National Health and Medical Research Council
Funding Amount
$581,524.00
Summary
We recently made the discovery that the virus that causes AIDS can be potently inhibited by stimulating a specific step in the virus life cycle. Our evidence suggests this stimulation is controlled by a host factor which will be identified in this study. Its discovery would be an important step towards a new means to fight HIV infection.