Novel Immune Evasion Strategy Of CMV: Targeting Of An Adhesion Molecule Involved In Leukocyte Recruitment/activation.
Funder
National Health and Medical Research Council
Funding Amount
$391,650.00
Summary
Herpesviruses cause persistent lifelong infection. To achieve this they have evolved a variety of mechanisms to evade the immune response mounted to combat them. They also minimise the expression of their gene products to a minimal suite of latency associated proteins. One member of the herpesvirus family is cytomegalovirus. While in healthy individuals it causes aymptomatic infection, it causes significant disease and mortality in individuals whose immune systems are suppressed such as transpla ....Herpesviruses cause persistent lifelong infection. To achieve this they have evolved a variety of mechanisms to evade the immune response mounted to combat them. They also minimise the expression of their gene products to a minimal suite of latency associated proteins. One member of the herpesvirus family is cytomegalovirus. While in healthy individuals it causes aymptomatic infection, it causes significant disease and mortality in individuals whose immune systems are suppressed such as transplant and AIDS patients, and also in the fetus which has a poorly developed immune system. Cytomegaloviruses set up persistent and latent lifelong infections. In the current proposal we will be assessing a viral gene present in mouse cytomegalovirus that codes for a protein that binds to a cellular adhesion molecule. This adhesion molecule called CD44 is involved in the migration of immune effector cell to sites of infection and in their activation. The viral gene thus represents a potential immune evasion molecule with the ability to subvert the host's immune response by reducing the infiltration and-or activation of cells that clear virus infection. The results from these studies could help us design anti-viral drugs that interfere with the effect of this viral protein, thus providing a novel anti-viral treatment strategy.Read moreRead less
Inhibition Of Endothelial Cell Adhesion Molecule Expression By High Density Lipoproteins
Funder
National Health and Medical Research Council
Funding Amount
$80,550.00
Summary
It is well known that high levels of cholesterol in blood cause coronary heart disease. However, it is also known that not all of the blood cholesterol is bad. If it is carried in particles called low density lipoproteins or LDLs it causes heart disease. But if it is carried in other particles known as high density lipoproteins or HDLs it does not. In fact, it is now well known that HDLs actually protect against the development of coronary heart disease. There are two main actions of HDLs that c ....It is well known that high levels of cholesterol in blood cause coronary heart disease. However, it is also known that not all of the blood cholesterol is bad. If it is carried in particles called low density lipoproteins or LDLs it causes heart disease. But if it is carried in other particles known as high density lipoproteins or HDLs it does not. In fact, it is now well known that HDLs actually protect against the development of coronary heart disease. There are two main actions of HDLs that contribute to their ability to protect. Firstly, they are known to drain cholesterol out of coronary arteries. We have recently shown that they have a second action. The end result of this second action is a slowing down of the entry into coronary arteries of cells called monocytes that are necessary for the development of the atherosclerosis that causes the heart disease. This project is concerned with this ability of HDLs to slow down the development of atherosclerosis by the second action. We have found that this second action of HDLs is influenced by the type of fats they carry. We propose now to investigate the mechanism by which different fats influence this action of HDLs with a view to devising new strategies for the prevention of heart disease.Read moreRead less
Investigation Of The Role For GPVI In Platelet Function And Thrombosis
Funder
National Health and Medical Research Council
Funding Amount
$542,772.00
Summary
Blood cells play an important role in maintaining healthy blood vessels. We are studying the role of platelets in blood clots following vessel injury. However, while critical for normal blood vessel maintenance, these cells also contribute to diseases including thrombosis. We will examine how an important platelet receptor called GPVI promotes blood clot formation, and examine whether combining anticoagulant drugs with GPVI deficient platelets leads to a more effective anticlotting approach.