EEF1A1 Is Critical For HIV-1 Reverse Transcription And Replication
Funder
National Health and Medical Research Council
Funding Amount
$521,429.00
Summary
The project will investigate interaction between the AIDS virus, HIV-1, and the human cell it grows in specifically focusing on a human protein called eEF1A. Our research shows eEF1A is required for HIV-1 growth by regulating a step in the virus life cycle called reverse transcription. The goal of this project is investigate how interaction with eEF1A helps HIV-1 reverse transcription and to find drugs that block HIV-1 interaction with eEF1A.
How Does A Host Cell Stimulatory Factor Stabilize The HIV-1 Reverse Transcription Complex?
Funder
National Health and Medical Research Council
Funding Amount
$631,883.00
Summary
We have identified a host cell activity which HIV uses to infect cells. The activity assists the uniques ability of HIV to convert its genome to a form which inserts itself into the host cell DNA. If we can identify the protein responsible for this activity we may be able to target it for drug development. Targetting host cell proteins rather than virus proteins for new drug may have advantages in preventing the acquisition of drug resistance.
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.
Investigating The Host Determinants Of Viral Clearance Versus Collateral Pathology In Chronic Infection
Funder
National Health and Medical Research Council
Funding Amount
$1,250,756.00
Summary
Hepatitis B virus has infected over 2 billion people. Some people control the virus but it remains incurable and there is a lifelong risk of liver cancer. Understanding how host cells interact with the virus, the mechanisms the cells use in an attempt to eliminate the virus and the mechanisms the virus uses to sabotage these responses, will provide insights that could lead to therapies. Potential therapies could be applicable to other infections like HIV-1 and tuberculosis.
Both human and viral genetic materials (ribonucleic acids, RNA) are made up of 4 different basic residues, namely A, U, G and C. Combination of any three of these ribonucleic acids residues is known as codon , which is essential to target one of the twenty amino acids to the host cell machinery for the making of proteins. Eighteen out of these twenty amino acids can be represented by more than one codon during the making of proteins. Interestingly, human and viral proteins, such as HIV-1, utilis ....Both human and viral genetic materials (ribonucleic acids, RNA) are made up of 4 different basic residues, namely A, U, G and C. Combination of any three of these ribonucleic acids residues is known as codon , which is essential to target one of the twenty amino acids to the host cell machinery for the making of proteins. Eighteen out of these twenty amino acids can be represented by more than one codon during the making of proteins. Interestingly, human and viral proteins, such as HIV-1, utilise two completely different subsets of codons (codon bias) for the synthesis of their respective proteins. The objective of this proposal is to delineate the functional requirement of this codon bias in HIV-1 replication cycle. Results from this work will identify novel elements that may be used for the design of novel antiretroviral strategy. Furthermore, lesson learned from this project will also provide important clues to improve the efficacy and safety of the design of current retroviral gene delivery vector.Read moreRead less
Control Of Viral Replication By Non-coding Viral RNA
Funder
National Health and Medical Research Council
Funding Amount
$502,270.00
Summary
In 25 years since identified, HIV-AIDS deaths have exceeded 30 million and 40 million more are now living with HIV. The toll will soon far surpass any other infectious disease epidemic in history, or even military deaths from war in the past century. While effective combination drug therapies are available, multi-drug resistant HIV strains are commonly transmitted, leaving some patients with limited treatment options. New classes of drugs aimed at different steps in virus replication are urgentl ....In 25 years since identified, HIV-AIDS deaths have exceeded 30 million and 40 million more are now living with HIV. The toll will soon far surpass any other infectious disease epidemic in history, or even military deaths from war in the past century. While effective combination drug therapies are available, multi-drug resistant HIV strains are commonly transmitted, leaving some patients with limited treatment options. New classes of drugs aimed at different steps in virus replication are urgently needed. We have discovered that viral RNAs that do not code for protein serve important functions in HIV replication. We will study the molecular mechanisms these non-coding (intron) RNAs previously considered junk use to support of HIV gene expression and assess their potential as drug targets. First, we will investigate the role of these junk RNA loops, or lariat introns, produced in large amounts during the HIV replication cycle. Retroviruses employ RNA splicing to make mRNA for envelope and regulatory accessory genes. The complex alternative RNA splicing pattern of HIV spawns several non-coding lariats, including the lariat-intron that contains much of the removed env coding sequence. We have made the counterintuitive finding that the env-lariat dramatically enhances expression of Env protein. We will examine how this occurs and the involvement of the new class of gene-expression controlling micro-RNAs in this process. We will test for functional activity from the other lariat-introns that are produced by HIV. Second, we will characterise the mRNA-element required for efficient expression of the HIV envelope glycoprotein, Env gp160, which is essential for virus binding and entry during infection. This RNA-element directs the cell protein translation machinery to commence protein synthesis at the start of the Envgp160 rather than at upstream start sites for Vpu and Rev. We will determine how this RNA element works, its structure, and how it might be inactivated.Read moreRead less
Comparative Expression Studies To Identify Cellular Factors Promoting Hendra Virus Replication For A Comprehensive Understanding Of Hendra Virus Pathogenesis
Funder
National Health and Medical Research Council
Funding Amount
$374,619.00
Summary
Hendra virus (HeV) is an emerging pathogen indigenous to fruit bats. HeV is associated with limited outbreaks with high mortality in domesticated animals and humans. To advance the understanding of HeV-related pathogenesis, we will perform comparative studies in bat and human cell lines to recognise differences in virus-host cell interactions leading to a comprehensive understanding of the HeV life cycle and pathogenesis.
A single vaccine for influenza and pneumonia. Influenza and bacterial pneumonia collaborate to kill millions of people each year. This project aims to develop a single vaccine that will provide long-lasting protection against both influenza and pneumonia.
Exploration Of The Role Of Microbes In Gastrointestinal Diseases
Funder
National Health and Medical Research Council
Funding Amount
$687,974.00
Summary
This fellowship will investigate diseases of the gastrointestinal tract of children. The research program will undertake a range of is a highly innovative projects including; development of an effective rotavirus vaccine to be administered to newborns; genetic characterisation of rotavirus strains able to escape vaccine protection; and how alterations in the human gut microbiome (bacteria and viruses) influence the development/relapse of CrohnÍs disease.
Discovery of Novel Respiratory Viruses Causing Influenza-Like Illness in Healthy Australian Adults Aged 18 to 64 Years. This work will inform our understanding of the causes of acute respiratory illnesses in Australia at the present time by looking for both known and previously undiscovered respiratory viruses. Increasing the knowledge base regarding causes of disease will have downstream relevance for health policy planners seeking to assess the burden of disease due to different causes. Early ....Discovery of Novel Respiratory Viruses Causing Influenza-Like Illness in Healthy Australian Adults Aged 18 to 64 Years. This work will inform our understanding of the causes of acute respiratory illnesses in Australia at the present time by looking for both known and previously undiscovered respiratory viruses. Increasing the knowledge base regarding causes of disease will have downstream relevance for health policy planners seeking to assess the burden of disease due to different causes. Early identification and description of new diseases will allow pre-emptive evaluation of new public health threats. This information will help to ensure availability and marketability of vaccines to prevent infection.Read moreRead less