Improving Treatment Strategies For Chronic Alphaviral Arthritic Diseases
Funder
National Health and Medical Research Council
Funding Amount
$643,624.00
Summary
Chikungunya virus and Ross River virus cause epidemics of acute and chronic arthritic disease in humans, which is often poorly managed with current treatments. This grant seeks to understand the mechanisms that give rise to disease in order to identify improved treatment strategies. Both the persistence of viral replication in joint tissues and unnecessary inflammatory responses appear to be important factors driving chronic disease.
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.
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.
Inhibition Of Interferon-alpah-beta By Chikungunya Virus And The Induction Of Arthritis
Funder
National Health and Medical Research Council
Funding Amount
$709,193.00
Summary
Chikungunya virus is a mosquito borne virus which has caused epidemics of arthritis around the world (recently 260,000 people Reunion Island, France and 1.6 million people in India). The virus is ordinarily very sensitive to the main mammalian anti-viral defence system (interferon alpha-beta). This grant seeks to understand how, despite the activation of this system during infection, the virus manages to persist and cause 3-6 months of debilitating arthritis.
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.
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.
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
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
Multiple Cytomegalovirus Infections: Biological And Evolutionary Significance.
Funder
National Health and Medical Research Council
Funding Amount
$555,776.00
Summary
This project involves the study of cytomegalovirus (CMV) a common viral infection of humans which normally cause little disease. However in individuals whose immune system is suppressed (such as AIDS patients or transplant recipients), or in infection of pregnant women, CMV can cause serious or life-threatening disease in the patient or foetus. An interesting feature of CMV diseases in such patients is that enhanced viral growth and more severe disease is frequently associated with the presence ....This project involves the study of cytomegalovirus (CMV) a common viral infection of humans which normally cause little disease. However in individuals whose immune system is suppressed (such as AIDS patients or transplant recipients), or in infection of pregnant women, CMV can cause serious or life-threatening disease in the patient or foetus. An interesting feature of CMV diseases in such patients is that enhanced viral growth and more severe disease is frequently associated with the presence of multiple strains of CMV in the patient. We suggest that mixed CMV infections provide a survival advantage to the virus, with different strains within the mixed infection assisting the growth of other strains. This would result in increased virus growth overall, and enhanced disease. To study the mechanisms by which multiple infections with different CMV strains may affect both the virus and the host, experiments will be performed using an animal model of CMV, murine cytomegalovirus (MCMV). We will examine the effect of the presence of multiple strains of virus on virus growth and distribution within the infected host. We will also determine if functional MCMV strains are capable of assisting non-functional strains to survive within the host. These studies are relevant to the design of a CMV vaccine, and will be valuable in revealing the ways in which viruses can co-operate within an infection.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.