Cell Surface Lectin Receptors For Attachment And Entry Of Influenza Viruses Into Cells Of The Innate Immune System
Funder
National Health and Medical Research Council
Funding Amount
$530,094.00
Summary
Influenza virus is a leading cause of respiratory infection and death worldwide. Infection of humans is initiated when the virus contacts cells lining the respiratory tract. Infection of epithelial cells leads to virus amplification whereas infection of immune cells results in virus destruction. Despite extensive research efforts, it is not clear how the virus infects these cells. This project aims to identify receptors on human cells used by influenza virus to attach to and infect immune cells.
The HIV-1 Tat Protein Is An Reverse Transcription Co-factor.
Funder
National Health and Medical Research Council
Funding Amount
$404,592.00
Summary
HIV-1 is the virus that causes AIDS. In order for HIV-1 to grow, the viral genetic material must be converted into a form that is compatible with a human host. Specifically, the HIV-1 genetic material is made of RNA while the human genome is composed of DNA. An HIV-1 enzyme called reverse transcriptase (RT) is used for this purpose. We have discovered that another HIV-1 protein called Tat is also required for the efficient conversion of HIV-1 RNA into HIV-1 DNA. If HIV-1 lacks Tat, then this tra ....HIV-1 is the virus that causes AIDS. In order for HIV-1 to grow, the viral genetic material must be converted into a form that is compatible with a human host. Specifically, the HIV-1 genetic material is made of RNA while the human genome is composed of DNA. An HIV-1 enzyme called reverse transcriptase (RT) is used for this purpose. We have discovered that another HIV-1 protein called Tat is also required for the efficient conversion of HIV-1 RNA into HIV-1 DNA. If HIV-1 lacks Tat, then this transformation process is inefficient and HIV-1 is not able to grow. Recently our group made a breakthrough discovery on how Tat works. Tat can directly bind to RT and stimulate the conversion process. This research is aimed at a detailed analysis of Tat and RT interaction. This information is required in order to understand how this interaction can be blocked in order to stop HIV-1 growth. In the long-term, results produced by this research will be required to discover novel drugs to combat HIV-AIDS.Read moreRead less
The Role Of Noncoding Subgenomic Flavivirus RNA In Virus-host Interactions
Funder
National Health and Medical Research Council
Funding Amount
$624,429.00
Summary
Flaviviruses such as Dengue, Japanese encephalitis , and West Nile are major human pathogens causing more than 50 million infections per year. Elements in viral genome responsible for pathogenesis of these viruses are not well defined. Recently we have identified a unique for these viruses noncoding subgenomic flavivirus RNA (sfRNA) and showed that it is contributing to viral pathogenesis. In this proposal we aim to determine mechanisms by which sfRNA facilitates viral pathogenesis.
Roles Of The Hepatitis C Virus Glycoprotein E2 Variable Regions In Virus Entry, Immunogenicity And Immune Evasion.
Funder
National Health and Medical Research Council
Funding Amount
$682,820.00
Summary
Hepatitis C Virus infects 200 million people world-wide with over 200,000 Australians infected with the disease. This project will examine how the surface proteins of HCV change their shape to evade antibody responses and how this effects the outcome of infection. We will further characterize a vaccine that elicits protective immunity to HCV to identify the optimal formulation for clinical trials.
The occcurence of herpes simplex virus (HSV) in the general population is very high (up to 60%). In Central Africa, co-infection of HSV and HIV may increase HIV transmission in more than 40% of cases. HSV enters the human body via the skin before entering the termini of nerve cell processes. It is transported along these processes to the body of the nerve cell. HSV lies dormant within these nerve cell bodies near the spinal cord in most people. Intermittently the virus reactivates and is transpo ....The occcurence of herpes simplex virus (HSV) in the general population is very high (up to 60%). In Central Africa, co-infection of HSV and HIV may increase HIV transmission in more than 40% of cases. HSV enters the human body via the skin before entering the termini of nerve cell processes. It is transported along these processes to the body of the nerve cell. HSV lies dormant within these nerve cell bodies near the spinal cord in most people. Intermittently the virus reactivates and is transported back down the nerve cell processes to the skin where it causes blisters-ulcers or is shed without causing symptoms. The aim of this project is to determine how HSV is assembled within cells at the molecular level. This will lead to identification of crucial molecular interactions required for viral assembly. Such information on viral assembly will allow development of inhibitors of this process which may be candidates for use as antivirals for control of recurrent herpes simplex. These antiviral agents will be able to target key viral molecular interactions in essentially all types of cells in the body and act against other herpesviruses in general.Read moreRead less
Functional Roles Of The Tegument Proteins Of Herpes Simplex Virus Type 1
Funder
National Health and Medical Research Council
Funding Amount
$461,597.00
Summary
The occurrence of herpes simplex virus (HSV) in the general population is very high (up to 60%). HSV enters the human body via the skin before entering nerve cells where it lies dormant in most people. Intermittently the virus reactivates and usually forms blisters at the skin when it sheds. The aim of this project is to define a molecular interaction network at the protein level during the course of infection of a host cell. This information will provide new targets for design of antivirals.
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