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.
Host-virus Interactions That Define The Outcome Of Anti-viral T Cell Responses: Relevance To Viral Persistence
Funder
National Health and Medical Research Council
Funding Amount
$487,500.00
Summary
Infection with human cytomegalovirus (hCMV) is normally resolved without symptomatic evidence of infection. However, severe hCMV disease can occur in immunocompromised patients in which the manifestations of disease include chorioretinitis, interstitial pneumonia and hepatitis. In immunologically immature children, congenital infection results in cytomegalic inclusion disease (CID). CID in infants causes severe neurological sequelae resulting in mental retardation, deafness and blindness. Vaccin ....Infection with human cytomegalovirus (hCMV) is normally resolved without symptomatic evidence of infection. However, severe hCMV disease can occur in immunocompromised patients in which the manifestations of disease include chorioretinitis, interstitial pneumonia and hepatitis. In immunologically immature children, congenital infection results in cytomegalic inclusion disease (CID). CID in infants causes severe neurological sequelae resulting in mental retardation, deafness and blindness. Vaccination against hCMV induced cytomegalic inclusion disease has been designated Level I (most favourable) due to the prediction that it could save lives and prevent life-long disability. Given the essential nature of CD8 T cells in CMV control and the high prevalence of CMV in society, it will be crucial to develop a vaccine capable of eliciting an efficacious T cell response which develops lasting memory. We hypothesise that mCMV has evolved mechanisms for generating an appropriate T cell response involved in viral control and the establishment of a persistent infection. The central aim of the work in the current proposal is to investigate the cellular and viral mechanisms involved in the generation of cytomegalovirus specific T cells. The proposed studies will improve our understanding of the generation of anti-viral T cell responses and hence will be relevent to further our understanding of the role of T cells in human infection. More importantly the results will provide critical insights into the rational design of suitable antiviral drugs and vaccines.Read moreRead less
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.
Research Fellowship: Immunoregulation And Immunity To Viral Infection
Funder
National Health and Medical Research Council
Funding Amount
$763,845.00
Summary
Award of this fellowship will ensure the continuation of a highly productive research program that over the last 15 years has made numerous seminal contributions to understanding the immune responses generated during viral infection. This multidisciplinary, highly collaborative program seeks to use this knowledge to develop effective therapies, both cellular and gene therapy-based, to treat viral infections and their complications by harnessing the immune system.
Effective Therapies To Treat Viral Infections And Their Complications In Transplantation
Funder
National Health and Medical Research Council
Funding Amount
$1,100,450.00
Summary
Viral infections are a common life threatening complication in transplant recipients, for which there are limited treatment options. We have developed several pre-clinical models that we are using to determine how the treatment of viral infections that occur after transplantation can be improved.
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.
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.
I am an infectious diseases physician and basic scientist interested in the immunopathogenesis of HIV and hepatitis B virus. My work focuses on HIV viral reservoirs and immune reconstitution and the adaptive immune response to hepatitis B virus.