Herpesviruses infect most Australians and cause recurrent ulcers, birth defects and cancer. Infection lasts lifelong, and spreads to close contacts without obvious clinical signs. Thus disease is hard to prevent. However we can learn much from related animal infections. We have shown that both mouse and human herpesviruses enter mice via cells in the nose. Thus human infections might follow the same route. We will define what body defences work here and whether vaccines can prevent infection.
Human ?-herpesviruses persist for life, cause cancers and emerge with particular virulence when the immune system is weak. Vaccination against them is therefore an important health priority. We have shown for a related ?-herpesvirus of mice that live vaccines protect. Antibody seems to play a major role. We will test whether safer, recombinant vaccines are also sufficient to elicit protective antibody. Thus we can establish a viable strategy for preventing virus-induced human cancers.
Studies On The Flavivirus Nonstructural Proteins And Untranslated Regions Of The Genome Involved In Virus Replication
Funder
National Health and Medical Research Council
Funding Amount
$244,277.00
Summary
Flaviviruses cause potentially fatal diseases of global importance such as yellow fever, Japanese encephalitis (JE) and dengue haemorrhagic fever. Flavivirus disease is also important in Australia with recurrent outbreaks of dengue fever, Australian encephalitis and more recently JE in the northern regions of the continent. Effective vaccines are only available to yellow fever and JE and tick-borne encephalitis and are either live or killed preparations which are potentially hazardous and costly ....Flaviviruses cause potentially fatal diseases of global importance such as yellow fever, Japanese encephalitis (JE) and dengue haemorrhagic fever. Flavivirus disease is also important in Australia with recurrent outbreaks of dengue fever, Australian encephalitis and more recently JE in the northern regions of the continent. Effective vaccines are only available to yellow fever and JE and tick-borne encephalitis and are either live or killed preparations which are potentially hazardous and costly to produce. There are no therapeutic agents (antivirals) available against flavivirus diseases. To produce safe and cost effective vaccines against flaviviruses and to identify targets for antiviral agents, a more complete understanding of how these viruses replicate in the cell and cause disease is required. This investigation aims to define specific aspects of the flavivirus life cycle that are currently unknown.Read moreRead less
Viral infections of the gut are one of the most debilitating infections one can suffer from. Noroviruses are the most common causative agents of viral-associated gastroenteritis but unfortunately little is known regarding their biology and pathogenesis. Our study aims to investigate the replication and pathogenesis of a mouse norovirus to shed light on similar aspects relating to human norovirus infection. We aim to understand how virus infection in cells leads to disease symptoms.
Defining The Requirement For The Inhibition Of Bak To The Pathogenesis Of Cytomegalovirus Infection
Funder
National Health and Medical Research Council
Funding Amount
$592,661.00
Summary
Apoptosis, or programmed cell death is a powerful defence mechanism against viral infection. Thus, to replicate efficiently viruses have evolved means to inhibit apoptosis. The central aim of this work is to understand how cytomegalovirus prevents cell death protein during infection. The proposed studies will improve our understanding of the mechanisms that regulate viral replication and will contribute insights into the normal processes that control cell survival.
Influenza A Virus PB1-F2 Protein: A Putative Virulence Factor And Initiator Of Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$474,718.00
Summary
Influenza virus produces a protein of undefined function called PB1-F2. Infection of mice with virus expressing PB1-F2 from virulent strains causes severe lung inflammation, while PB1-F2 from milder seasonal viruses does not. We will examine how PB1-F2 influences virulence of human influenza in the ferret, which exhibits the same illness as humans. This work will help understand the disease severity of newly evolved influenza viruses of humans and the role of PB1-F2 in mediating this.
Understanding HIV Resistance To Entry Inhibitors To Advance The Development Of Novel Antivirals
Funder
National Health and Medical Research Council
Funding Amount
$877,585.00
Summary
We cannot afford to be complacent in the search for improved anti HIV drugs for 2 principal reasons; First, worldwide a staggering 66% of infected individuals who need treatment are still unable to access therapy; and Second, the main reason why most treated patients are now living longer and more healthy lives is because we have never stopped developing newer therapies to provide options for patients. In this study we will develop and test newer drugs that block HIV infection of cells.
Current combination antiviral therapy can't cure an HIV infection because long-lived T-cells carrying latent HIV DNA can rekindle the infection when drugs are removed. We will study elements in HIV genetic code that control expression of HIV proteins from latent HIV. A detailed molecular understanding of the structure and function of these HIV RNA elements and the viral and host cell factors that interact with them will expose new targets for therapy of latent HIV.