Department of Medicine, Laboratory Medicine, Global Health Medicine, University of Washington, Seattle, WA 98195, USA.
Proc Natl Acad Sci U S A. 2010 Nov 2;107(44):18973-8. doi: 10.1073/pnas.1006614107. Epub 2010 Oct 18.
Herpes simplex virus-2 (HSV-2) shedding episodes in humans vary markedly in duration and virologic titer within an infected person over time, an observation that is unexplained. To evaluate whether host or virological factors more closely accounted for this variability, we combined measures of viral replication and CD8(+) lymphocyte density in genital biopsies, with a stochastic mathematical model of HSV-2 infection. Model simulations reproduced quantities of virus and duration of shedding detected in 1,003 episodes among 386 persons. In the simulations, local CD8(+) lymphocyte density in the mucosa at episode onset predicted peak HSV DNA copy number and whether genital lesions or subclinical shedding occurred. High density of CD8(+) T cells in the mucosa correlated with decreased infected cell lifespan and fewer infected epithelial cells before episode clearance. If infected cell lifespan increased by 15 min because of CD8(+) lymphocyte decay, then there was potential for a thousandfold increase in the number of infected cells. The model suggests that the rate of containment of infected cells by the peripheral mucosal immune system is the major driver of duration and severity of HSV-2 reactivation in the immunocompetent host.
人类单纯疱疹病毒 2 型（HSV-2）的脱落期在一个感染者体内随时间变化而显著变化，其病毒学滴度和持续时间均有不同，这种现象目前仍无法解释。为了评估是宿主因素还是病毒因素更能解释这种可变性，我们将生殖器活检中的病毒复制和 CD8+淋巴细胞密度的测量值与 HSV-2 感染的随机数学模型相结合。模型模拟再现了 386 名患者的 1003 次脱落期的病毒数量和持续时间。在模拟中，发病时粘膜局部的 CD8+淋巴细胞密度可预测 HSV DNA 拷贝数峰值以及是否出现生殖器病变或无症状脱落。粘膜中 CD8+T 细胞的高密度与感染细胞寿命缩短和清除前感染上皮细胞数量减少有关。如果由于 CD8+淋巴细胞衰减而使感染细胞寿命增加 15 分钟，则感染细胞数量可能会增加一千倍。该模型表明，外周粘膜免疫系统对感染细胞的控制速度是免疫功能正常宿主中 HSV-2 再激活的持续时间和严重程度的主要驱动因素。
