Stress Hormones Epinephrine and Corticosterone Selectively Reactivate HSV-1 and HSV-2 in Sympathetic and Sensory Neurons.
Stress Hormones Epinephrine and Corticosterone Selectively Reactivate HSV-1 and HSV-2 in Sympathetic and Sensory Neurons.
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DOI：
10.3390/v14051115
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发表时间：
2022-05-23
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影响因子：
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单纯疱疹病毒1型和2型（HSV-1和HSV-2）在感觉神经元和自主神经元中建立潜伏期，它们可以在宿主的整个生命中重新激活以引起复发性疾病。应激与人类和动物模型中的HSV复发密切相关。然而，应激激素作用于潜伏病毒引起再激活的机制尚不清楚。我们发现，应激激素肾上腺素（EPI）和皮质酮（CORT）诱导HSV-1的再激活选择性交感神经元，但不感觉或副交感神经元。多种肾上腺素能受体的激活是EPI诱导的HSV-1再激活所必需的，而CORT需要糖皮质激素受体。相反，CORT，而不是EPI，通过糖皮质激素或盐皮质激素受体诱导HSV-2在感觉和交感神经元中的再激活。再活化依赖于EPI和CORT的不同转录因子，并且与病毒基因表达的快速变化一致，尽管HSV-1和HSV-2的基因不同，并且EPI和CORT的时间动力学不同。因此，应激诱导的再激活机制是神经元特异性、刺激特异性和病毒特异性的。这些发现对HSV-1和HSV-2复发性疾病模式和频率的差异，以及开发可能作用于不同类型神经元中不同反应的靶向，更有效的抗病毒药物具有意义。
Herpes simplex viruses 1 and 2 (HSV-1 and HSV-2) establish latency in sensory and autonomic neurons, from which they can reactivate to cause recurrent disease throughout the life of the host. Stress is strongly associated with HSV recurrences in humans and animal models. However, the mechanisms through which stress hormones act on the latent virus to cause reactivation are unknown. We show that the stress hormones epinephrine (EPI) and corticosterone (CORT) induce HSV-1 reactivation selectively in sympathetic neurons, but not sensory or parasympathetic neurons. Activation of multiple adrenergic receptors is necessary for EPI-induced HSV-1 reactivation, while CORT requires the glucocorticoid receptor. In contrast, CORT, but not EPI, induces HSV-2 reactivation in both sensory and sympathetic neurons through either glucocorticoid or mineralocorticoid receptors. Reactivation is dependent on different transcription factors for EPI and CORT, and coincides with rapid changes in viral gene expression, although genes differ for HSV-1 and HSV-2, and temporal kinetics differ for EPI and CORT. Thus, stress-induced reactivation mechanisms are neuron-specific, stimulus-specific and virus-specific. These findings have implications for differences in HSV-1 and HSV-2 recurrent disease patterns and frequencies, as well as development of targeted, more effective antivirals that may act on different responses in different types of neurons.
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DOI：
10.1073/pnas.251194298
发表时间：
2001-11-20
影响因子：
11.1
作者：
Bennett, BL;Sasaki, DT;Anderson, DW
通讯作者：
Anderson, DW
影响因子：
5.4
作者：
Bertke, Andrea S.;Ma, AyeAye;Margolis, Todd P.
通讯作者：
Margolis, Todd P.
影响因子：
5.4
作者：
Halford, WP;Kemp, CD;Schaffer, PA
通讯作者：
Schaffer, PA
影响因子：
7.4
作者：
Gold, MS;Dastmalchi, S;Levine, JD
通讯作者：
Levine, JD
影响因子：
64.8
作者：
Fryer, CJ;Archer, TK
通讯作者：
Archer, TK