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

dc.contributor.authorGoswami, Poornaen
dc.contributor.authorIves, Angela M.en
dc.contributor.authorAbbott, Amber R. N.en
dc.contributor.authorBertke, Andrea S.en
dc.date.accessioned2022-06-01T19:18:44Zen
dc.date.available2022-06-01T19:18:44Zen
dc.date.issued2022-05-23en
dc.date.updated2022-05-27T13:36:31Zen
dc.description.abstractHerpes 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.en
dc.description.versionPublished versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationGoswami, 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.en
dc.identifier.doihttps://doi.org/10.3390/v14051115en
dc.identifier.urihttp://hdl.handle.net/10919/110386en
dc.language.isoenen
dc.publisherMDPIen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectherpes simplex virusen
dc.subjectHSV-1en
dc.subjectHSV-2en
dc.subjectepinephrineen
dc.subjectcorticosteroneen
dc.subjectreactivationen
dc.subjectprimary adult neuronsen
dc.subjectautonomic neuronsen
dc.subjectsensory neuronsen
dc.titleStress Hormones Epinephrine and Corticosterone Selectively Reactivate HSV-1 and HSV-2 in Sympathetic and Sensory Neuronsen
dc.title.serialVirusesen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten

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