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.
Viral Factors Involved In Flavivirus Replication And Virus-host Interactions
Funder
National Health and Medical Research Council
Funding Amount
$743,696.00
Summary
With our increased understanding of virus-host interactions it has become apparent that small, non-structural proteins and small RNAs of most viruses are vital for numerous, often multiple, functions in the viral life cycle. In the proposed project, we seek to gain a detailed understanding of the functions of small nonstructural protein NS2A and small abundant viral RNAs of medicaly important encephalitic flaviviruses, which have remained so far elusive and are at the cutting-edge in the researc ....With our increased understanding of virus-host interactions it has become apparent that small, non-structural proteins and small RNAs of most viruses are vital for numerous, often multiple, functions in the viral life cycle. In the proposed project, we seek to gain a detailed understanding of the functions of small nonstructural protein NS2A and small abundant viral RNAs of medicaly important encephalitic flaviviruses, which have remained so far elusive and are at the cutting-edge in the research field. We anticipate that with a better understanding of the roles of these factors in flaviviral replication and pathogenesis, novel targets for antiviral therapies and-or molecular determinants for inclusion in candidate vaccines will be identified.Read moreRead less
Comparative Expression Studies To Identify Cellular Factors Promoting Hendra Virus Replication For A Comprehensive Understanding Of Hendra Virus Pathogenesis
Funder
National Health and Medical Research Council
Funding Amount
$374,619.00
Summary
Hendra virus (HeV) is an emerging pathogen indigenous to fruit bats. HeV is associated with limited outbreaks with high mortality in domesticated animals and humans. To advance the understanding of HeV-related pathogenesis, we will perform comparative studies in bat and human cell lines to recognise differences in virus-host cell interactions leading to a comprehensive understanding of the HeV life cycle and pathogenesis.
Exploration Of The Role Of Microbes In Gastrointestinal Diseases
Funder
National Health and Medical Research Council
Funding Amount
$687,974.00
Summary
This fellowship will investigate diseases of the gastrointestinal tract of children. The research program will undertake a range of is a highly innovative projects including; development of an effective rotavirus vaccine to be administered to newborns; genetic characterisation of rotavirus strains able to escape vaccine protection; and how alterations in the human gut microbiome (bacteria and viruses) influence the development/relapse of CrohnÍs disease.
Norovirus Infection At The Stress Granule-PKR-p-elF2α Axis
Funder
National Health and Medical Research Council
Funding Amount
$505,967.00
Summary
This project application will aim to investigate and understand how viruses that cause vomiting and diarrhoea are able to infect, proliferate and spread within the human body. It aims to address how viruses are able to avoid and replicate in the presence of an effective immune response. We have evidence showing that Noroviruses are able to exploit certain antiviral proteins to paradoxically aid in virus replication and survival.
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
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