Research ArticleHerpes Simplex Virus

Frequent Release of Low Amounts of Herpes Simplex Virus from Neurons: Results of a Mathematical Model

Science Translational Medicine  18 Nov 2009:
Vol. 1, Issue 7, pp. 7ra16
DOI: 10.1126/scitranslmed.3000193

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Herpes simplex virus 2 (HSV-2), a sexually transmitted infection, is the leading cause of genital ulcers worldwide. Infection is lifelong and is characterized by repeated asymptomatic and symptomatic episodes of virus shedding that are initiated when virus is released from neurons into the genital tract. The pattern of HSV-2 release from neurons, which harbor the virus, into the genital tract is poorly understood. We fit a mathematical model of HSV-2 pathogenesis to curves generated from daily quantification of HSV in mucosal swabs from patients with herpetic genital ulcers. We used virologic parameters derived from model fitting for stochastic model simulations. These simulations reproduced previously documented estimates for shedding frequency and herpetic lesion diameter and frequency. The most realistic model output occurred when we assumed that the amount of virus shed from neurons daily was minimal. In our simulations, small changes in the average total quantity of HSV-2 released from neurons influenced the frequency of detectable shedding, whereas changes in the frequency of HSV-2 neuronal release had little effect. Frequent HSV-2 shedding episodes in humans are explained by nearly constant release of small numbers of viruses from neurons that terminate in the genital tract.


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