Determinants Of Cytomegalovirus Salivary Gland Persistence
Funder
National Health and Medical Research Council
Funding Amount
$566,308.00
Summary
Human cytomegalovirus (HCMV) persists for extended periods in the salivary gland, an organ of viral transmission. It is not clear how the virus avoids immune mediated control in this tissue. This aspect of viral pathology will be assessed in a mouse model using two strains of murine CMV which exhibit marked differences in salivary gland persistence. The role of tissue tropism (inhibition of apoptosis), viral immune evasion and host immunity in salivary gland persistence will be studied.
Effects Of Natural Sequence Variation On Evasion Of Cytotoxic T Lymphocytes By Murine Cytomegalovirus.
Funder
National Health and Medical Research Council
Funding Amount
$553,167.00
Summary
Human cytomegalovirus persists for the life time of an infected person. It has many ways of achieving this, including interfering with the host immune response. This project seeks to explore this using a mouse model and murine CMV. Specifically we will focus on a set of viral genes that inhibit host recognition of virally infected cells. Sequence variation in these genes suggests that they function differently in different strains of virus: we will examine the consequences of this variation.
Defining A Novel Mechanism Of Control Of Host Functions By Human Cytomegalovirus That Enhances Viral Pathogenesis
Funder
National Health and Medical Research Council
Funding Amount
$616,518.00
Summary
Human cytomegalovirus (HCMV) remains a significant human pathogen which causes serious and often life-threatening disease in immunosuppressed people such as bone marrow and solid organ transplant patients and in unborn babies infected during pregnancy. This project will define how HCMV controls host defences by actively modifying the cells it infects to create an environment favourable to continued viral infection and disease.
Defining A Virally-encoded Molecular Switch Between Productive And Latent Phases Of Human Cytomegalovirus Infection.
Funder
National Health and Medical Research Council
Funding Amount
$337,614.00
Summary
Human cytomegalovirus (HCMV) is a significant human pathogen which causes serious disease in immunosuppressed people such as bone marrow and solid organ transplant patients. HCMV has the capacity to switch between an active and a dormant state, enabling this virus to remain within the human host, where it can emerge years later to cause disease in immunosuppressed people. This project will define how HCMV controls the switch between active and dormant phases of infection.
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
The Balance Of Signals Received By NK Cells Is Modulated By Viruses As A Mean Of Immune Escape.
Funder
National Health and Medical Research Council
Funding Amount
$583,175.00
Summary
Cytomegalovirus (CMV) affects about 60% of the population in Australia. Infection is partially controlled by the immune system but CMV is never eliminated and people remain carriers for the rest of their life. Reactivation of CMV in healthy individuals is usually asymptomatic, but it causes severe diseases in people with immune deficiencies. We seek to discover the mechanisms used by CMV to escape immune surveillance, in order to gain insights into the development of improved antiviral therapies
Understanding How Cytomegaloviruses Establish Systemic Infection
Funder
National Health and Medical Research Council
Funding Amount
$668,144.00
Summary
Human cytomegalovirus (HCMV) infects most Australians, causes birth defects and harms transplant patients. Vaccines against it have worked poorly. HCMV spreads throughout the body and is never cleared. To control infection we must identify its key checkpoints. Using mouse CMV, we find that host dendritic cells, which normally defend against infections, are taken over and spread virus to new sites. The viral gene responsible is a potential target for intervention. We will define how it works.
Prophylactic Vaccine To Prevent Cytomegalovirus Disease
Funder
National Health and Medical Research Council
Funding Amount
$436,360.00
Summary
This project is aiming to develop a prophylactic vaccine against a common herpesvirus which has been linked to the birth defects in new born babies and significant morbidity and mortality in transplant patients. In this project we are testing a novel nanoparticle-based vaccine formulation which stimulates the immune system with single injection and the immunity induced is sustained for long-term.
Is There Cytomegalovirus In Mothers Breastmilk And Does It Cause Infection In Very Premature Babies?
Funder
National Health and Medical Research Council
Funding Amount
$235,970.00
Summary
The hypothesis behind this study is that some very premature infants become infected with cytomegalovirus (CMV) from their mother's breast milk. This proposal is for a study of 200 CMV antibody positive mothers who are expressing breast milk for their very premature infants. We believe this is likely to be about 50% of all mothers. It has been well established that some full term infants are infected with CMV from their mother's breastmilk. The question now is do very premature infants with poor ....The hypothesis behind this study is that some very premature infants become infected with cytomegalovirus (CMV) from their mother's breast milk. This proposal is for a study of 200 CMV antibody positive mothers who are expressing breast milk for their very premature infants. We believe this is likely to be about 50% of all mothers. It has been well established that some full term infants are infected with CMV from their mother's breastmilk. The question now is do very premature infants with poor immunity develop serious infections from cytomegalovirus. This project has the overall aim of determining what proportion of very premature infants become ill with CMV excreted in their mother's breast milk, and then determining the nature and severity of those illnesses. It will also define how many mothers of premature infants are excreting CMV in their breast milk, the time this starts after birth, the viral load transmitted to the infant, the age after birth when the infants first become infected, the proportion who become ill with the infection, the details of the diseases and whether freezing breast milk kills the CMV.Read moreRead less