Transport And Egress Of Herpes Simplex Virus In Neurones
Funder
National Health and Medical Research Council
Funding Amount
$592,023.00
Summary
Herpes simplex virus (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 grant is to determine how HSV is transpor ....Herpes simplex virus (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 grant is to determine how HSV is transported within nerve cells at the molecular level. Recent discoveries have shown how virus transport in nerve cells is dependent on interactions between specific viral proteins and cellular motor proteins and how the virus escapes from nerves to infect skin and cause disease. Such information on viral transport will allow development of inhibitors of this process which may be candidates for use as antivirals for control of recurrent herpes simplex. In addition, this information will allow the virus to be exploited for use in gene therapy to introduce DNA into human nerve cells to correct genetic abnormalities. Finally this data will assist in understanding similar mechanisms for other viruses transported in nerve cells such as those causing shingles and rabies.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.
Solving Delivery Of Gene Therapy For Control Of Human Immunodeficiency Virus Infection
Funder
National Health and Medical Research Council
Funding Amount
$765,439.00
Summary
Antiretroviral therapy free control of Human Immunodeficiency Virus (HIV) infection requires control of the viral reservoir. We have a unique approach, aimed at enforcing HIV latency by targeting highly conserved regions in the viral promoter. These constructs completely silence viral transcription for long periods of time. We intend to develop & assess vectors that are specifically targeted to the reservoir and which can enforce viral latency despite immune activation or viral variation.
Cell Type Specific Biologic Responses To HIV Infection
Funder
National Health and Medical Research Council
Funding Amount
$636,242.00
Summary
The way in which HIV alters the internal environment of its target cells to facilitate its growth will be examined. These changes enhance its ability to gain a toehold in the human body after entering the genital tract and its persistence for life in the brain and elsewhere in the body.
Pathogenesis Of Persistent Human Virus Infections Of Global Significance
Funder
National Health and Medical Research Council
Funding Amount
$6,571,328.00
Summary
The study will investigate why humans cannot eradicate particular viruses (HIV-AIDS, cytomegalovirus and herpes simplex virus), the long term effects of these viruses and ways to improve control. Current treatments can only partly suppress the levels of these viruses, because they persist in certain parts of the body called reservoirs, only to resurge later causing disease. Thus, the overall aim of the research program is to discover the mechanisms by which these viruses are able to successfully ....The study will investigate why humans cannot eradicate particular viruses (HIV-AIDS, cytomegalovirus and herpes simplex virus), the long term effects of these viruses and ways to improve control. Current treatments can only partly suppress the levels of these viruses, because they persist in certain parts of the body called reservoirs, only to resurge later causing disease. Thus, the overall aim of the research program is to discover the mechanisms by which these viruses are able to successfully persist within reservoirs in the human body. The research program brings together a group of 6 leading scientists and clinicians located at 3 sites in 2 Australian cities. The team is comprised of experts in the study of HIV-AIDS, cytomegalovirus and herpes simplex virus who will combine their knowledge and expertise to speed up the process of research on these viruses that are of major health importance. Studies will also utilise a number of cutting edge technologies that now make it possible to much more rapidly and precisely determine how viruses cause disease. Advances in our understanding of how viruses persist may form the basis for treatments aimed at controlling persistent infections and the serious diseases caused by these viruses.Read moreRead less
HIV-1 Transcriptional Gene Silencing By Promoter Targeted Si/shRNAs: Uncovering Mechanisms, Optimising Delivery Systems, Assessing In Vivo Efficacy.
Funder
National Health and Medical Research Council
Funding Amount
$641,789.00
Summary
Current therapy for HIV is effective but must be taken for life. If therapy is stopped the virus comes back immediately from reservoirs not affected by current drugs. These fluctuating levels of virus are associated with increased illness and death. We are exploring a method of inducing prolonged viral latency using short double stranded RNA molecules. We propose to understand the mechanism of action of these possible therapeutics and to develop these constructs towards use in clinical trials.
Arbovirus Activation And Modulation Of NLRP3 Inflammasome
Funder
National Health and Medical Research Council
Funding Amount
$779,720.00
Summary
This project aims to establish how mosquito borne viruses such as Ross River and dengue viruses interacts with the human host to cause disease, including how the virus evades the host’s immune response to persist and cause disease for prolonged periods. Knowing how differences in the virus and the host’s immune system interplay to cause asymptomatic to severely disabling disease will assist in devising new treatments and prevention programs to lessen the impact of these diseases in Australia.
New Insights Into Viral Inflammatory Disease Mechanisms And Approaches To Therapy
Funder
National Health and Medical Research Council
Funding Amount
$631,010.00
Summary
This fellowship aims to establish how viruses cause disease, including how they evade the immune response to persist and cause disease for prolonged periods. My vision is that knowing how the virus and the immune system interact to determine disease severity will assist in devising new treatments and prevention programs to lessen the impact of viral diseases in Australia and worldwide.
Mosquito-borne alphaviruses such as Ross River and chikungunya viruses cause widespread epidemics and exert extreme pressure on the public health systems of affected regions. Alphaviruses spreads to joints and triggers a severe disease in those affected. There are no effective treatments or vaccines. The project will investigate virus-host interaction at the bite site. The outcome will be new knowledge to treat infection at the mosquito bite site to prevent joint disease.
Novel Insights Into The Pathobiology Of Alphavirus Infections
Funder
National Health and Medical Research Council
Funding Amount
$827,660.00
Summary
Infections with mosquito-borne viruses are increasing at an alarming rate worldwide. Ross River virus is endemic in parts of Australia, PNG and Pacific islands, while chikungunya virus is distributed globally and causes recurrent pandemics that involve millions of people. These viruses cause severe musculoskeletal disease for several months after infection. This project aims to establish how these viruses interact with the human host to cause disease and may provide a basis for new treatments.