Grant: Operating Grant

Upon infection our body's immune system must ramp up to control the infection; then, once the infection is eliminated, the immune system goes back to its resting state and our symptoms disappear. But what happens when the immune system cannot get rid of the infection? This leads to chronic infection, such as occurs with human immunodeficiency virus (HIV), Hepatitis B and C viruses. If the immune system stayed fully active during chronic infection we would damage our body through excess inflammation. Thus, the immune system has evolved ways of reducing the immune response during chronic infection. This has the advantage of preventing death from inflammation, but the disadvantage that one ends up with a life-long infection that can have long-term negative consequences. My laboratory is studying a family of molecules that are induced on white blood cells during viral infections. These molecules help the white blood cells clear the infection. We recently asked what happens to these molecules during a chronic infection when the immune system can't get rid of the virus. We found that during prolonged infection one such immune stimulatory molecule was still there but no longer worked. We further investigated and found that the immune stimulatory molecule on the surface of the white blood cell no longer worked because one of the molecules its uses to send signals inside the white blood cell had been degraded. Our proposal is aimed at asking how other members of this family of molecules behave during chronic infection and in understanding the processes that allow enlarged spleens to shrink back to normal and reorganize after a long infection. The results of these studies will inform new therapeutic approaches aimed at the chronic stage of HIV infection.