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.
Understanding The Role Of Ongoing Viral Activity In Herpes Simplex Virus Latency
Funder
National Health and Medical Research Council
Funding Amount
$980,762.00
Summary
The virus that causes cold sores and genital herpes has a dormant phase from which renewed infection can recur. We recently discovered that this dormant phase is more active than we thought and we now want to learn how the body acts to suppress the virus so that these defence mechanisms might be improved to stop recurrent infections.
A Humanised Mouse Model For Herpes Simplex Virus Pathogenesis
Funder
National Health and Medical Research Council
Funding Amount
$277,109.00
Summary
Herpes simplex virus (HSV) causes cold sores and genital herpes, diseases that persist and recur. This persistence is because HSV has several ways of stopping the body from detecting and eliminating the cells that it infects. This project will generate new tools that will help us to understand one of the ways that HSV hides from our defences and may be useful in developing immune-based therapies to treat the infection.
Defining The Mechanism Of Assembly Of Herpes Simplex Virus In The Neuronal Growth Cone And Its Subsequent Exit To Epithelial Cells
Funder
National Health and Medical Research Council
Funding Amount
$774,624.00
Summary
Herpes simplex virus (HSV) causes dormant infection of nerve cell bodies near the spine. It periodically reactivates to be transported along nerves to the skin where it causes oral, genital or neonatal herpes and mediates HIV superinfection. HSV assembles into its final form in the terminal part of the axon just prior to crossing into skin. Elucidating the mechanism of HSV assembly and exit will facilitate new strategies for antiviral agents and immune treatment for HSV and similar viruses.
The Mechanism Of HSV-1 Transport In Sensory Axons And Its Unique Assembly At The Axon Terminus
Funder
National Health and Medical Research Council
Funding Amount
$670,284.00
Summary
Herpes simplex viruses 1 and 2 cause common diseases such as genital herpes and, occasionally, neonatal deaths and encephalitis and predisposes to HIV infection. New antiviral strategies are required for resistant viruses for control. These aims will be facilitated by understanding how HSV is transported down nerves and across into skin. In this study, we will define how a key viral protein plays a major role in assembly of the virus at the tip of the nerve before it enters skin.
Defining The Contribution Of Skin Gamma Delta T Cells To Cutaneous Immunosurveillance, Immunity And Disease After HSV Infection.
Funder
National Health and Medical Research Council
Funding Amount
$601,386.00
Summary
Herpes simplex virus (HSV) causes genital herpes and encephalitis. Disease is severe in the immunocompromised and the newborn. HSV enters through breaks in the skin or mucosa, where it first encounters gamma delta T cells. We have recently made the key finding that HSV can infect gamma delta T-cells shortly after inoculation. Here we will study how they contribute to the immune response when a virus enters the skin in mice and human tissues. This may lead development of new topical antiviral vac ....Herpes simplex virus (HSV) causes genital herpes and encephalitis. Disease is severe in the immunocompromised and the newborn. HSV enters through breaks in the skin or mucosa, where it first encounters gamma delta T cells. We have recently made the key finding that HSV can infect gamma delta T-cells shortly after inoculation. Here we will study how they contribute to the immune response when a virus enters the skin in mice and human tissues. This may lead development of new topical antiviral vaccines.Read moreRead less
Structural Basis Of Substrate Recognition By The Membrane-Associated E3 Ubiquitin Ligases
Funder
National Health and Medical Research Council
Funding Amount
$415,244.00
Summary
Membrane-associated E3 ubiquitin ligases control cellular levels of important immunoregulatory molecules and occur in both host- and virus-encoded forms. Target selectivity maps to the transmembrane domains of ligases and their substrates in a little-studied mode of intramembrane molecular recognition. Our goal is to determine the physical basis of this interaction by establishing which sequences drive the association and providing atomic-resolution structures of the membrane-embedded complexes.
Regulation Of Tissue-Resident Memory T Cell Development
Funder
National Health and Medical Research Council
Funding Amount
$494,554.00
Summary
A recently identified subset of T cells that reside in the skin are critical to combat viral infection. However, little is known about how these T cell populations are formed. This project will characterise the pathways required to generate these cells and will identify novel factors that regulate their development. A greater understanding of how these T cells can be generated will open the way to utilise these cells in new vaccine strategies.
Initial Interactions Of Herpes Simplex Virus With Innate Immune Cells In Human Skin
Funder
National Health and Medical Research Council
Funding Amount
$522,589.00
Summary
Herpes simplex viruses 1 and 2 cause widespread and occasionally serious diseases including genital herpes, neonatal death and encephalitis. Current vaccine candidates are at best partially effective. This grant will examine the way that the virus enters, initially spreads within the skin and interacts with immune cells to help determine which cells should be stimulated by vaccines.
Topical microbicides are urgently required to protect women from the sexual transmission of HIV. Lactic acid is produced by bacteria that are normally present in the healthy female vaginal tract and is more potent in the inactivation of HIV compared to low pH alone. This study seeks to determine how lactic acid inactivates HIV and to undertake laboratory studies to determine its suitability for development as a topical microbicide to prevent HIV transmission.