Frequent release of low amounts of herpes simplex virus from neurons: results of a mathematical model.
Frequent release of low amounts of herpes simplex virus from neurons: results of a mathematical model.
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DOI：
10.1126/scitranslmed.3000193
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发表时间：
2009-11-18
影响因子：
17.1
通讯作者：
Corey L
中科院分区：
文献类型：
--
作者：
Schiffer JT;Abu-Raddad L;Mark KE;Zhu J;Selke S;Magaret A;Wald A;Corey L
单纯疱疹病毒-2（HSV-2）是一种性传播感染，是全球生殖器溃疡的主要原因。感染是终身的，其特征是病毒从神经元释放到生殖道时开始的反复无症状和有症状的病毒脱落发作。人们对HSV-2从神经元释放到生殖道的模式知之甚少。我们将HSV-2发病机理的数学模型拟合到从疱疹性生殖器溃疡患者的粘膜拭子中进行的HSV每日定量产生的曲线。我们使用来自随机模型模拟模型拟合的病毒学参数。这些模拟再现了先前记录的散毒频率、疱疹病变直径和频率的估计值。当我们假设每天神经元病毒的引入量最小时，模型输出最真实。在我们的模拟中，从神经元释放的HSV-2的平均总量的微小变化会影响可检测的脱落频率，而神经元HSV-2释放频率的变化几乎没有影响。人类中频繁的HSV-2脱落事件可以解释为终止于生殖道的神经元几乎持续释放少量病毒。
Herpes Simplex Virus-2 (HSV-2) is a sexually transmitted infection that is the leading cause of genital ulcers worldwide. Infection is life long and is characterized by repeated asymptomatic and symptomatic shedding episodes of virus that are initiated when virus is released from neurons into the genital tract. The pattern of HSV-2 release from neurons 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 performed 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 minimal amounts of daily neuronal virus introduction. In our simulations, small changes in average total quantity of HSV-2 released from neurons influenced detectable shedding frequency, while changes in frequency of neuronal HSV-2 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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