Grant: Operating Grant

Epstein-Barr virus (EBV) infects about 95% of the world's population. Although EBV doesn't cause serious problems in most people, EBV is the cause of a number of important cancers including Burkitt lymphoma, which is the most common childhood cancer in much of Africa. EBV also causes infectious mononucleosis ("mono") in substantial fraction of all adolescents and young adults in the developed world. Mono is not lethal, but results in enormous health care costs and missed school/work. A vaccine to prevent EBV infection or its associated diseases would be an invaluable global health intervention. Although there has been progress toward developing an effective EBV vaccine, more needs to be known about exactly how infection occurs, and how the immune system controls infection. To study this, we followed a group of families with a newborn baby in Uganda, where EBV infects virtually 100% of children by 3 years of age and the rate of Burkitt lymphoma is the highest in the world. A study clinician went to each of these family's homes every week for a year, tested the infants and their family members for EBV infection, examined the baby, and asked extensive questions about risk factors for infection and symptoms of illness. This represents the most comprehensive study of EBV infection ever performed. We precisely determined the time the babies became infected with EBV to within one week, and will be able to analyze what demographic and behavioral factors increase the risk of infection, and describe what symptoms of illness occur. Now we propose to go further, and use samples that were collected from these families to examine the genetic variation of the EBV strains that they were infected with, and to study what immune factors might prevent EBV infection or help to control the infection once it occurs. This type of information is essential to deciding what kind of EBV vaccine might be most effective, and to have the best chance of preventing EBV-related illness and cancer.