Postdoc Giao Huynh publishes two papers about the Epstein-Barr virus

Postdoc Giao Huynh, of the Department of Mathematics and Statistics, has published two papers recently. Both papers use mathematical modeling to study the Epstein-Barr virus, one of the most common viruses in humans. The first, Modeling the Dynamics of Virus Shedding into the Saliva of Epstein-Barr Virus Positive Individuals, is in collaboration with CBR member Libin Rong, and appeared in the October issue of the Journal of Theoretical Biology (Volume 310, Pages 105-114).

"Abstract: Epstein-Barr virus (EBV) can infect both B cells and epithelial cells. Infection of B cells enables the virus to persist within a host while infection of epithelial cells is suggested to amplify viral output. Data from a recent study have shown that the virus shedding in EBV positive individuals is relatively stable over short periods of time but varies significantly over long periods. The mechanisms underlying the regulation of virus shedding within a host are not fully understood. In this paper, we construct a model of ordinary differential equations to study the dynamics of virus shedding into the saliva of infected hosts. Infection of epithelial cells is further separated into infection by virus released from B cells and virus released from epithelial cells. We use the model to investigate whether the long-term variation and short-term stability of virus shedding can be generated by three possible factors: stochastic variations in the number of epithelial cells susceptible to virus released from infected B cells, to virus released from infected epithelial cells, or random variation in the probability that CD8(+) T cells encounter and successfully kill infected cells. The results support all three factors to explain the long-term variation but only the first and third factors to explain the short-term stability of virus shedding into saliva. Our analysis also shows that clearance of virus shedding is possible only when there is no virus reactivation from B cells."

The second, Mathematical Modeling the Age Dependence of Epstein-Barr Virus Associated Infectious Mononucleosis, was written with collaborator Frederick Adler, of the University of Utah, and appeared in the September issue of Mathematical Medicine and Biology-A Journal of the IMA (Volume 29, Pages 245-261).

"Abstract: Most people get Epstein-Barr virus (EBV) infection at young age and are asymptomatic. Primary 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."

While working in Rong’s mathematical modeling group, Huynh’s research was supported by a National Institutes of Health grant (P30EB011339) to support a Core Center for Quantitative Biology, and a $189,000 National Science Foundation (http://www.nsf.gov) award (1122290) to Rong.