Immune Modulatory Effects Of Vaginal Microbiota Metabolites And HIV Susceptibility
Funder
National Health and Medical Research Council
Funding Amount
$795,110.00
Summary
This study will advance knowledge on how acid molecules produced by beneficial and harmful bacteria are able to promote or impede HIV infection of the female genital mucosa through their effects on the barrier and immune function of cells that line the vagina and cervix. The results of this study are anticipated to augment the efficacy of topical HIV prevention strategies and lead to the development of safe vaginal hygiene products that help protect against other sexually transmitted infections.
HIV/AIDS remains a major global threat with ?37 million individuals living with HIV in 2014. Antiretroviral drugs have transformed HIV from a death sentence into a chronic disease. Public health organisations recommend dramatic scale up of drugs for HIV treatment and prevention. However, a major threat is that drug options will be exhausted in the long-term due to drug resistance and toxicity. The major aim of this study is to advance the development of an entirely new drug class for HIV.
Elucidating The Mechanism Of Action Of Dendrimer Nanoparticles Against HIV
Funder
National Health and Medical Research Council
Funding Amount
$559,354.00
Summary
Dendrimers are nanoparticles with highly branched structures and they are being developed as topical microbicides to prevent the sexual transmission of HIV. This study will determine how dendrimers block HIV entry into host cells so that we can design more effective inhibitors and microbicides.
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.
Discovery Of A Novel Immune Evasion Strategy Employed By Mosquito Borne Viruses To Suppress Antiviral Immune Responses
Funder
National Health and Medical Research Council
Funding Amount
$418,642.00
Summary
The transition from mosquitoes, ticks, or other invertebrate vectors to the human hosts represents a crucial step in the successful establishment of arthropod borne viruses (arboviruses). The incidence of arbovirus infections such as dengue virus, West Nile virus, Ross River virus is increasing at an alarming rate in various parts of the world. In addition, the emergence of new viruses resulting in significant mortality in the population is of utmost concern. Vaccines for many of these viruses r ....The transition from mosquitoes, ticks, or other invertebrate vectors to the human hosts represents a crucial step in the successful establishment of arthropod borne viruses (arboviruses). The incidence of arbovirus infections such as dengue virus, West Nile virus, Ross River virus is increasing at an alarming rate in various parts of the world. In addition, the emergence of new viruses resulting in significant mortality in the population is of utmost concern. Vaccines for many of these viruses remain elusive. One factor that contributes to this is the ability of viruses to develop ingenious strategies to avoid or suppress the host defence systems, which enable its successful establishment in the host. Understanding how viruses evade-suppress host defence machinery will certainly enhance and improve our approaches to fight them. For the first time internationally we have discovered a new and novel pathway employed by arboviruses to suppress antiviral immune responses in the host. We have discovered that naturally occurring carbohydrates on viruses derived from mosquito cells, would influence these virus s ability to evade-suppress host antiviral proteins such as interferons. This may be a general effect of arboviruses or may even extend to other viruses , which include a number of deadly pathogens (HIV, Influenza). This research has the potential to significantly expand our understanding of how these viruses establish infection and cause disease. Also this discovery has broader implications for understanding inflammatory processes and their regulation.Read moreRead less
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.
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
Influenza remains an important disease and exacts a high toll in both morbidity and mortality each year. This project will identify the carbohydrates that are utilised by influenza virus to initiate infection throughout the body and map how these carbohydrates interact with the key viral surface proteins. This research will provide new insight into the emergence of new influenza virus strains and cross-species pathogenicity.