Mathematical Biology Seminar

Joshua Schiffer
University of Washington & Fred Hutchinson Cancer Research Center
Wednesday, February 22nd, 2012
3:05pm in LCB 323
"Herpes Simplex Virus-2 Infection: An Intense, Lifelong Compromise Between Host and Pathogen"

HSV-2 infection is the most common cause of genital ulcers worldwide. Because HSV-2 enhances HIV-1 acquisition and transmission, and can cause severe disease in the newborn and in immunocompromised hosts, this infection is of significant public health importance. Infection is characterized by frequent and heterogeneous viral reactivations in the genital tract, implying that although viral latency is maintained in the neural ganglia, HSV-2 frequently manages to bypass latency control mechanisms. Immune control in genital skin and mucosa is characterized by intense, highly localized, and persistent infiltrates of CD4+ and CD8+ T-cells. I will describe our group's detailed spatio-temporal characterization of HSV-2 shedding and immune response, along with stochastic mathematical models that describe the complex and nearly constant interactions between replicating virus and host immune cells. These models predict that viral-host interactions within single plaques of viral replication occur on a much more rapid time scale than previously appreciated, and that concurrent foci of replication explain prolonged viral shedding. More recent models generate hypotheses for why currently antiviral therapies are only partially effective, and for why vaccine development poses a substantial challenge.