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"
Abstract:
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.
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