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Stress Hormones Epinephrine and Corticosterone Selectively Reactivate HSV-1 and HSV-2 in Sympathetic and Sensory Neurons

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dc.creator Goswami, Poorna
dc.creator Ives, Angela M.
dc.creator Abbott, Amber R. N.
dc.creator Bertke, Andrea S.
dc.date 2022-06-01T19:18:44Z
dc.date 2022-06-01T19:18:44Z
dc.date 2022-05-23
dc.date 2022-05-27T13:36:31Z
dc.date.accessioned 2023-03-01T18:54:59Z
dc.date.available 2023-03-01T18:54:59Z
dc.identifier Goswami, P.; Ives, A.M.; Abbott, A.R.N.; Bertke, A.S. Stress Hormones Epinephrine and Corticosterone Selectively Reactivate HSV-1 and HSV-2 in Sympathetic and Sensory Neurons. Viruses 2022, 14, 1115.
dc.identifier http://hdl.handle.net/10919/110386
dc.identifier https://doi.org/10.3390/v14051115
dc.identifier.uri http://localhost:8080/xmlui/handle/CUHPOERS/281888
dc.description 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.
dc.description Published version
dc.format application/pdf
dc.format application/pdf
dc.language en
dc.publisher MDPI
dc.rights Creative Commons Attribution 4.0 International
dc.rights http://creativecommons.org/licenses/by/4.0/
dc.title Stress Hormones Epinephrine and Corticosterone Selectively Reactivate HSV-1 and HSV-2 in Sympathetic and Sensory Neurons
dc.title Viruses
dc.type Article - Refereed
dc.type Text


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