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
Development Of National Protocols For The Detection Of Influenza A H5N1
Funder
National Health and Medical Research Council
Funding Amount
$248,229.00
Summary
This project will develop a best practice approach to the diagnosis of influenza A H5N1 (Bird Flu) in Australian public health laboratories. Tests such as reverse transcription polymerase chain reaction (RT-PCR) are in use globally for influenza A H5N1 detection. Some proprietary rapid influenza A tests also claim to detect influenza A H5N1. However there is little information on systematic evaluation of these, largely because there have been relatively few human influenza A H5N1 cases and patie ....This project will develop a best practice approach to the diagnosis of influenza A H5N1 (Bird Flu) in Australian public health laboratories. Tests such as reverse transcription polymerase chain reaction (RT-PCR) are in use globally for influenza A H5N1 detection. Some proprietary rapid influenza A tests also claim to detect influenza A H5N1. However there is little information on systematic evaluation of these, largely because there have been relatively few human influenza A H5N1 cases and patient specimens. Australian laboratories need authoritative guidelines as to optimal influenza tests, target genes and reagents. Development of a simple, potentially automated type specific test for influenza A H5N1 antibody such as enzyme immunoassay (EIA) is also desirable, as widely used tests cannot distinguish between infection with H5 or other influenza types. Reference methods such as haemagglutination inhibition (HAI) are cumbersome. In this project mock specimens for virus and antibody detection will be created using viral cell culture and infected chicken derived influenza A H5N1. This will be undertaken in physical containment level 4 (PC4) facilities in Australia's designated human and animal PC4 laboratories. This material will be used for (i) specimen panels to compare the performance of candidate laboratory tests (ii) positive control material in all tests undertaken and (iii) quality assurance exercises to ensure high standards of testing. Using these panels the group will assess influenza H5N1 RT-PCR, tests for detection of influenza proteins including immunofluorescence, and rapid point of care influenza A detection tests available in Australia. An EIA method currently used to detect influenza antibodies from different animal species will be refined to develop a simple test for type specific detection influenza A H5N1 antibodies, and subsequently evaluated using animal sera. A standard method for HAI reference serology for use in public health laboratories will also be recommended, and the best approaches to high throughput automated RT-PCR, and performing RT-PCR in the field on portable instrumentation will be explored. Recommendations for standard protocols for influenza A H5N1 will be developed and will submitted for review and endorsement by Commonwealth ministerial advisory committees.Read moreRead less