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The Role Of A Novel Cytokine Of The Innate Immune Response In Viral Infection
Funder
National Health and Medical Research Council
Funding Amount
$344,407.00
Summary
Sexually transmitted infections represent a critical global health and socioeconomic problem with over 1 billion new cases per annum. I propose a world-first description of a new protein that has a protective role against herpes simplex virus (HSV) infection of female reproductive tract. This unique protein, called interferon epsilon, was discovered in our laboratory. This project will facilitate development of new therapeutic approaches of benefit in HSV-2 infection.
Anti-viral Immunity And The Survival Of Cells Infected With Herpes Simplex Virus In Vivo
Funder
National Health and Medical Research Council
Funding Amount
$574,890.00
Summary
Herpes simplex virus causes cold sores and genital herpes. A person can only catch the virus once in their life, but it stays in their body and can cause occasional outbreaks of disease. This recurrent disease can be frequent and severe. The place where the herpes virus hides in a dormant state between outbreaks is in the nervous system. This project aims to learn more about how the virus becomes dormant and also whether the immune system is important in keeping the virus in this state.
Interactions Between Herpes Simplex Viral And Neuronal Motor Proteins
Funder
National Health and Medical Research Council
Funding Amount
$222,962.00
Summary
Herpes simplex virus (HSV) lies dormant within the nerve cell bodies near the spinal cord in most people. Intermittently the virus reactivates and is transported down the nerve to the skin where it causes blisters-ulcers or is shed without causing symptoms. The aim of this grant is to determine how Herpes Simplex virus is transported within nerve cells at the molecular level. It builds on recent discoveries of a direct interaction between a Herpes simplex viral protein and the nerve cell motor p ....Herpes simplex virus (HSV) lies dormant within the nerve cell bodies near the spinal cord in most people. Intermittently the virus reactivates and is transported down the nerve to the skin where it causes blisters-ulcers or is shed without causing symptoms. The aim of this grant is to determine how Herpes Simplex virus is transported within nerve cells at the molecular level. It builds on recent discoveries of a direct interaction between a Herpes simplex viral protein and the nerve cell motor protein which transports essential components down nerves from the spinal cord to the skin. Ultimately we aim to develop inhibitors of this process which might be candidates for further development as antivirals for control of recurrent herpes simplex.Read moreRead less
The Biology Of Events Following Reactivation Of Herpes Simplex Virus.
Funder
National Health and Medical Research Council
Funding Amount
$388,522.00
Summary
Herpes simplex virus causes genital herpes, severe disease in neonates, cold sores and occasionally fatal encephalitis. It lies doemant within nerve cells near the spine and reactivates intermittently, travelling down nerves to cause the characteristic ulcers in the skin, including the genitals. This grant has two major components. In the first we aim to continue studies which are defining the way in which Herpes simplex viruses assemble within nerve cells. These processes have always been the s ....Herpes simplex virus causes genital herpes, severe disease in neonates, cold sores and occasionally fatal encephalitis. It lies doemant within nerve cells near the spine and reactivates intermittently, travelling down nerves to cause the characteristic ulcers in the skin, including the genitals. This grant has two major components. In the first we aim to continue studies which are defining the way in which Herpes simplex viruses assemble within nerve cells. These processes have always been the subject of much debate and have never been properly studied in the nerve cells in which the virus lives. Furthermore the way in which herpes simplex virus enters the processes of nerve cells and moves to the cell body will be studied by similar techniques. Such studies may contribute to the development of herpes simplex virus as a vector for gene therapy for treatment of diseases of the nervous system. The second part of the grant will examine the immune processes that occur in the skin during the early stages of a recurrent herpes simplex lesion. In particular there is a linkage between nerves and the major cells in the skin which present viral antigen to defensive T-cells. This link may provide a route for direct access of herpes simplex virus to these cells. In previous work the viral protein targets in infected skin cells for killer T-cells which infiltrate the skin have been defined. In this grant we also aim to find the stretches of amino acids which are specifically targetted by these cells.Read moreRead less
Molecular Pathogenesis Of Herpes Simplex Virus Latency And Reactivation : Relationship With Viral Genomic Structure
Funder
National Health and Medical Research Council
Funding Amount
$217,060.00
Summary
A major target for antiviral drugs that combat herpes simplex infections, such as genital herpes and herpes encephalitis, is replication of viral DNA. There are significant gaps in the understanding of herpes simplex virus DNA replication which are addressed in this project. Further, a major factor responsible for the high impact of herpes simplex on the community is virus' ability to lie dormant (latent) in the body. The significance of lateny is that it periodically reactivates giving rise to ....A major target for antiviral drugs that combat herpes simplex infections, such as genital herpes and herpes encephalitis, is replication of viral DNA. There are significant gaps in the understanding of herpes simplex virus DNA replication which are addressed in this project. Further, a major factor responsible for the high impact of herpes simplex on the community is virus' ability to lie dormant (latent) in the body. The significance of lateny is that it periodically reactivates giving rise to recurrent infections. In molecular terms, latency is a reversible interruption of viral DNA replication, but the precise mechanisms involved are incompletely understood. This project explores ways in which latency might be established and reactivated. This information may eventually lead to improved strategies for reducing the burdens caused by herpes simplex virus infections.Read moreRead less
The Generation Of HSV-1 Specific Effector And Memory CD4+ T Cell Responses.
Funder
National Health and Medical Research Council
Funding Amount
$460,509.00
Summary
This proposal aims to determine the mechanisms underpinning the generation of helper T cell responses following HSV-1 infection. It will determine the factors that allow T cells to access sites of viral replication and the mechanisms by which they provide protection from skin infections.
Assembly And Transport Of Herpes Simplex Virus Within Neurones
Funder
National Health and Medical Research Council
Funding Amount
$475,500.00
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 and assemblied 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. Such information on viral transport and assembly mechanisms will allow development of inhibitors of these processes 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.Read moreRead less
Transport, Assembly And Egress Of Herpes Simplex Virus In Neurones
Funder
National Health and Medical Research Council
Funding Amount
$639,661.00
Summary
Herpes simplex viruses 1 and 2 are important pathogens, causing encephalitis, blindness and severe neonatal infection but they also enhance the acquisition of HIV three-fold. The transport of the virus to and from the periphery to the spinal cord is a key component of their life cycle. Determination of the exact mechanism will assist in a general understanding of nerve function and the development of new strategies for antiviral drugs.
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