Grant: Operating Grant

When an individual is infected with a virus, white blood cells of our immune system are mobilized to fight the infection. One kind of white blood cell, called a cytotoxic or killer T cell, is important in killing virus-infected cells. During an acute viral infection the virus replicates for a few days and makes us ill, but within a week or so, the immune system succeeds in fully clearing the infection. However, sometimes the immune system cannot handle the infection, such as with HIV infection, and the infection becomes chronic. Under these conditions, the cytotoxic T cells can become inactivated. Our laboratory has shown that we can reactivate these T cells outside the body to kill HIV-infected cells. Therefore we wondered why the T cells are not working within the infected individuals. We found that a molecule called Tumor necrosis factor receptor associated factor 1 (or TRAF1) is important in the T cells in fighting HIV infection, but it disappears from the T cells over time of chronic infection. We would like to know why this happens more in some individuals than others and the mechanisms involved. TRAF proteins show small sequence differences among different individuals in the population, referred to as polymorphisms. We will investigate how these polymorphisms in TRAF proteins affect the ability of individuals to respond to acute infections such as influenza, as well as chronic infections, such a HIV. Understanding the role of TRAF1 and TRAF protein polymorphisms in immunity to acute viral infections, such as influenza, as well as chronic viral infections, such as HIV, will help us to design better vaccines and therapeutics.