Mathematical modeling the age dependence of Epstein-Barr virus associated infectious mononucleosis

Most people get Epstein-Barr virus (EBV) infection at young age and are asymptomatic. Pri-mary EBV infection in adolescents and young adults however, often leads to infectious mononucleosis (IM) with symptoms including fever, fatigue, and sore throat that can persist for months. Expansion in the number of CD8+ T cells, especially against EBV lytic proteins, are the main cause of these symptoms. We propose a mathematical model for the regulation of EBV infection within a host to address the dependence of IM on age. This model tracks the number of virus, infected B cell and epithelial cell, and CD8+ T-cell responses to the infection. We use this model to investigate three hypotheses for the high incidence of IM in teenagers and young adults: saliva and antibody effects that increase with age, high cross-reactive T-cell responses, and a high initial viral load. The model supports the first two of these hypotheses, and suggests that variation in host antibody responses and the complexity of the pre-existing cross-reactive T cell repertoire, both of which depend on age, may play important roles in the etiology of IM.