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.
Functions Of Viral Chemokine Receptor Homologues Important For Cytomegalovirus Pathogenesis And Latency
Funder
National Health and Medical Research Council
Funding Amount
$461,597.00
Summary
Cytomegalovirus (CMV) causes life-threatening disease in babies, transplant recipients and HIV-AIDS patients. We will focus on a CMV gene that has been 'hijacked' from the host cell and enables the virus to switch on signalling molecules within infected cells. We will determine how these signals enable CMV to infect sites of the body that are critical for virus transmission and contribute to long-term virus persistence. Our results will provide new strategies for drugs against CMV.
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
HIV Phenotypes Important For The Establishment Of Persistent Reservoirs In The Central Nervous System And Which Impact Neurotropism And Neuropathogenesis
Funder
National Health and Medical Research Council
Funding Amount
$762,492.00
Summary
This grant will determine whether or not the CNS is a reservoir for HIV and identify the cellular targets of persistent infection and type of HIV-1 present.
A Virus-like Particle Vaccine For Hepatitis C Virus.
Funder
National Health and Medical Research Council
Funding Amount
$199,013.00
Summary
The aim is to evaluate the efficiency of a virus-like particle (VLP) vaccine for hepatitis C virus (HCV). HCV infects about 10,000 people every year in Australia and approximately 8, 000 of these will develop persistent infection. As a result, there are currently 150,000-200,000 HCV carriers in Australia and 500 million worldwide. These individuals represent a source of infection. Although the major route for transmission is blood and blood products, the advent of HCV screening in the blood bank ....The aim is to evaluate the efficiency of a virus-like particle (VLP) vaccine for hepatitis C virus (HCV). HCV infects about 10,000 people every year in Australia and approximately 8, 000 of these will develop persistent infection. As a result, there are currently 150,000-200,000 HCV carriers in Australia and 500 million worldwide. These individuals represent a source of infection. Although the major route for transmission is blood and blood products, the advent of HCV screening in the blood banks has reduced the risk of infection from this source. However, many intravenous drug users (IVD) share needles and although it is not common, transmission to spouses of carriers is well recognised. In addition, approximately 20% of HCV carriers have no recognised risk factor and it is unclear how these individuals became infected. Transmission of the virus to hospital inpatients and outpatients is also well recognised and as a result, it is clear that a vaccine is urgently required. However, as HCV cannot be cultured in the laboratory, it is impossible to develop a traditional vaccine; furthermore, because a proportion of patients who recover from HCV infection have no specific immunity and thus can be re-infected, the design of a vaccine presents a number of problems. Thus a vaccine which is based on the development of neutralising antibody is unlikely to be effective, in contrast to a vaccine which is designed to generate a cellular immune response. VLPs induce an effective cellular immune response and we plan to make VLPs composed of the L1 protein of bovine papillomavirus (BPV) which is fused to the highly immunogenic HCV core protein or to a string of protein segments (polytope). Laboratory mice will be vaccinated with these VLP and the cellular immune response measured. The vaccine will then be administered to HCV carriers to ensure the safety and the immunological efficacy of the product. This will be assessed serologically and clinically.Read moreRead less
Memory CD4 T Cells That Harbour The Reservoir Of Latent HIV Infection: Their Antigen Specificity, Function And Frequency Of Antigen-drivien Reactivation
Funder
National Health and Medical Research Council
Funding Amount
$133,351.00
Summary
Current antiretroviral therapy for HIV-1 infection is able to suppress viral replication, but cannot eradicate it completely. Upon cessation of antiviral therapy, viral recrudescence is prompt, and most likely arises from latent reservoirs of HIV in various cellular compartments. The aim of this research is to characterise which subsets of CD4 T cells that are the target of HIV infection harbour HIV infection, including describing their function and individual target antigen specificities.
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.
Pathogenesis Of Persistent Human Virus Infections Of Global Significance
Funder
National Health and Medical Research Council
Funding Amount
$6,571,328.00
Summary
The study will investigate why humans cannot eradicate particular viruses (HIV-AIDS, cytomegalovirus and herpes simplex virus), the long term effects of these viruses and ways to improve control. Current treatments can only partly suppress the levels of these viruses, because they persist in certain parts of the body called reservoirs, only to resurge later causing disease. Thus, the overall aim of the research program is to discover the mechanisms by which these viruses are able to successfully ....The study will investigate why humans cannot eradicate particular viruses (HIV-AIDS, cytomegalovirus and herpes simplex virus), the long term effects of these viruses and ways to improve control. Current treatments can only partly suppress the levels of these viruses, because they persist in certain parts of the body called reservoirs, only to resurge later causing disease. Thus, the overall aim of the research program is to discover the mechanisms by which these viruses are able to successfully persist within reservoirs in the human body. The research program brings together a group of 6 leading scientists and clinicians located at 3 sites in 2 Australian cities. The team is comprised of experts in the study of HIV-AIDS, cytomegalovirus and herpes simplex virus who will combine their knowledge and expertise to speed up the process of research on these viruses that are of major health importance. Studies will also utilise a number of cutting edge technologies that now make it possible to much more rapidly and precisely determine how viruses cause disease. Advances in our understanding of how viruses persist may form the basis for treatments aimed at controlling persistent infections and the serious diseases caused by these viruses.Read moreRead less
Worldwide >360 million people have chronic hepatitis B virus (HBV) infection that imparts a 25% lifetime risk of death due to serious liver disease. Current therapies for chronic HBV reduce levels of virus replication but fail to target the stable, nuclear episome, covalently closed circular DNA (cccDNA). The current study will determine what is required to eliminate cccDNA and how current therapies for chronic HBV infection should be modified to achieve this aim.