Pathogenic Flaviviruses: Molecular Mechanisms Of Disease, Host Response And Vaccines
Funder
National Health and Medical Research Council
Funding Amount
$697,209.00
Summary
The application is aimed at advancing our understanding of the viral and host processes determining outcome of infection with pathogenic flaviviruses (i.e. West Nile virus) to the level allowing most comprehensive design of effective vaccines and anti-viral drugs. One of the aims is also to develop novel viral delivery vectors for cancer therapy based on self-replicating RNA of an attenuated Australian strain of West Nile virus, Kunjin.
The Phylodynamics Of Human Enteroviruses: Informing Vaccine Effectiveness And Outbreak Preparedness
Funder
National Health and Medical Research Council
Funding Amount
$564,868.00
Summary
Enteroviruses such as EV-A71 are increasing in frequency and in Australia have resulted in the hospitalization of children with severe encephalitis. However, major aspects of their evolution and epidemiology are unknown. We will provide new insights on these important pathogens by revealing which enteroviruses are circulating in the region and whether they arise in specific localities, whether some are commonly associated with severe encephalitis, and whether some pose a greater epidemic threat.
Intrinsic Host Antiviral Activity Against Pathogenic Filoviruses
Funder
National Health and Medical Research Council
Funding Amount
$488,754.00
Summary
Bats are a major reservoir for deadly human viruses including Ebola and Marburg virus. In contrast to humans, bats can be infected with these viruses without showing clinical signs of disease. The reason why bats can co-exist with these viruses is unknown. This study will determine if a bat antiviral molecule contributes to limiting virus release compared to the human version that could reveal strategies to prevent and control these deadly viruses in humans.
The Role Of Paramyxovirus P Protein Subcellular Trafficking In Virus Pathogenicity And Antagonism Of Host Interferon Responses
Funder
National Health and Medical Research Council
Funding Amount
$78,491.00
Summary
Emerging zoonotic viruses pose a major health threat worldwide, highlighted by recent outbreaks of viruses such as Nipah and Hendra via interspecies invasion to infect humans. A major barrier to interspecies infection is the innate immune response, which viruses must evolve to combat before successful infection can occur. We aim to examine in detail the mechanisms underlying immune evasion of such viruses, with the ultimate goal of discovering novel targets for therapeutics to viral infection.
Molecular Characterisation Of Host Cell Targets Of Human Pathogenic Viruses And Evaluating Their Potential As Novel Therapeutic Targets.
Funder
National Health and Medical Research Council
Funding Amount
$307,946.00
Summary
There are currently no therapeutics to treat victims of Hendra, Nipah or Rabies virus infections, which account for > 50,000 deaths/yr worldwide. Through not fully understood mechanisms, these viruses affect the functions of specific cellular proteins in order to inhibit the host immune system, a process essential to their pathogenicity. We aim to characterise the mechanisms underlying viral inhibition of host immunity and evaluate their potential as novel targets to develop urgently needed t ....There are currently no therapeutics to treat victims of Hendra, Nipah or Rabies virus infections, which account for > 50,000 deaths/yr worldwide. Through not fully understood mechanisms, these viruses affect the functions of specific cellular proteins in order to inhibit the host immune system, a process essential to their pathogenicity. We aim to characterise the mechanisms underlying viral inhibition of host immunity and evaluate their potential as novel targets to develop urgently needed therapeutics against these deadly pathogens.Read moreRead less
Burden Of Respiratory Infection In The First 2 Years Of Life: A Birth Cohort Study Of Emerging Respiratory Pathogens.
Funder
National Health and Medical Research Council
Funding Amount
$1,168,963.00
Summary
Respiratory illnesses are extremely common, but there is little information about patterns of infection in the community using modern diagnostic tests. Children have the highest rates of infection and transmit to all other age groups. We intend to recruit 138 newborns to monitor respiratory symptoms and collect specimens for testing in the first two years of life. This will allow us to document illnesses due to known and newly identified respiratory pathogens.
CHARACTERISATION OF NOVEL PICORNAVIRUS-LIKE VIRUSES IDENTIFIED FROM PATIENTS WITH ACUTE RESPIRATORY INFECTIONS.
Funder
National Health and Medical Research Council
Funding Amount
$366,998.00
Summary
The common cold and serious chest colds are usually due to viral infections, and mostly occur in children. Unfortunately we can only be certain of the virus causing this illness in as little as 15% of cases. We intend to address this lack of research by examining, in detail, a new virus we recently identified in a child with serious respiratory illness that required admission to hospital. Testing by our laboratory suggests that the new virus is related to picornaviruses (which cause some common ....The common cold and serious chest colds are usually due to viral infections, and mostly occur in children. Unfortunately we can only be certain of the virus causing this illness in as little as 15% of cases. We intend to address this lack of research by examining, in detail, a new virus we recently identified in a child with serious respiratory illness that required admission to hospital. Testing by our laboratory suggests that the new virus is related to picornaviruses (which cause some common colds) but seems to be present in children with far more serious illness. Our study plans to more completely identify the new picornavirus-like virus (PLV) using the tools of molecular biology and the expertise of a senior team of Australian scientists and clinicians who have recently made several virus discoveries in Australia, demonstrating that Australian virus research is capable of achieving highly competitive results that benefit our hospitals and especially their young patients. Our studies will develop extremely sensitive tests which rely on the detection of very small amounts of the viral genome. We can use these tests to determine what the whole virus looks like, when it might occur during the year and whether the PLV are found worldwide. Our studies will also produce viral proteins in the laboratory and use these to make new tests for stored blood samples. If a blood sample comes from a patient who has previously been infected by PLV, their blood will contain specific antibodies which we will then be able to detect. We also intend to determine whether some strains of PLV are more or less likely to cause serious illness than others. Improved understanding of these and other viruses minimises the chance of illness spreading within a hospital, helps scientists to decide against which viruses to design vaccines and drugs and aids medical doctors to better identify what once went undiagnosed.Read moreRead less
Development and commercialization of novel diagnostic assays for the early detection of acute dengue virus infection. Dengue is an emerging disease of the tropics and is endemic in more than 100 countries with up to 100 million cases annually. Of these, 500,000 result in dengue haemorrhagic fever (DHF), a serious life-threatening complication of dengue virus infection. Dengue activity in northern Australia has increased in recent years with suggestions that it may be coming endemic in this count ....Development and commercialization of novel diagnostic assays for the early detection of acute dengue virus infection. Dengue is an emerging disease of the tropics and is endemic in more than 100 countries with up to 100 million cases annually. Of these, 500,000 result in dengue haemorrhagic fever (DHF), a serious life-threatening complication of dengue virus infection. Dengue activity in northern Australia has increased in recent years with suggestions that it may be coming endemic in this country. Early diagnosis, using NS1 based assays should facilitate containment of such outbreaks through earlier identification, treatment, isolation and strategic mosquito control.Read moreRead less
Virulence Determinants Of Encephalitic Flaviviruses
Funder
National Health and Medical Research Council
Funding Amount
$455,670.00
Summary
Murray Valley encephalitis, Japanese enecephaltis virus and West Nile virus are mosquito transmitted pathogens that cause severe and fatal neurological diseases in man and animals. Currenly, it is not clear why these viruses produce such severe diseases and therefore they are difficult to treat and prevent. In this project we will indentify the components of the viruses that allow them to invade the central nervous sytem and cause neurological symptoms. This will provide valuable information on ....Murray Valley encephalitis, Japanese enecephaltis virus and West Nile virus are mosquito transmitted pathogens that cause severe and fatal neurological diseases in man and animals. Currenly, it is not clear why these viruses produce such severe diseases and therefore they are difficult to treat and prevent. In this project we will indentify the components of the viruses that allow them to invade the central nervous sytem and cause neurological symptoms. This will provide valuable information on critical elements of these pathogenic viruses that contribute to their virulence and will identify new candidate vaccines for prevention of the encephalitic diseases they cause.Read moreRead less
The dynamics of viral latency in chronic infection. Although many acute infections can now be controlled, we still suffer from a large number of chronic infections such as HIV or herpes that cannot be eradicated. Many of these infections persist because they can lie dormant in a 'latent' state. How this latent state is established, and how long it lasts are important to understand if we want to control these infections. We have assembled a team of mathematicians, immunologists and virologists in ....The dynamics of viral latency in chronic infection. Although many acute infections can now be controlled, we still suffer from a large number of chronic infections such as HIV or herpes that cannot be eradicated. Many of these infections persist because they can lie dormant in a 'latent' state. How this latent state is established, and how long it lasts are important to understand if we want to control these infections. We have assembled a team of mathematicians, immunologists and virologists in order to study latent infection at the cellular level, and within infected monkeys. This will provide the first insights into the dynamics of latency - how these cells are produced and die - and should lead to novel approaches to controlling chronic infection.Read moreRead less