HIV Maturation

Funded Activity Summary

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.

Funded Activity Details

Start Date: 01-01-2006

End Date: 01-01-2008

Funding Scheme: NHMRC Project Grants

Funding Amount: $283,767.00

Funder: National Health and Medical Research Council

Research Topics

ANZSRC Field of Research (FoR)

Medical Virology

ANZSRC Socio-Economic Objective (SEO)

There are no SEO codes available for this funding activity

Other Keywords

HIV-1/AIDS | HIV/AIDS | antiretrovirals | drug resistance | human immunodeficiency virus type 1 | protein-protein interaction | reverse transcriptase | virus replication

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