A Novel Link between Stress and Human Cytomegalovirus (HCMV) Infection: Sympathetic Hyperactivity Stimulates HCMV Activation
2000; Elsevier BV; Volume: 272; Issue: 2 Linguagem: Inglês
10.1006/viro.2000.0367
ISSN1096-0341
AutoresSusanna Prösch, Cornelia E.C. Wendt, Petra Reinke, Christina Priemer, Michael Oppert, Detlev H. Krüger, Hans‐Dieter Volk, Wolf‐Dietrich Döcke,
Tópico(s)Toxoplasma gondii Research Studies
ResumoRecently, inflammatory mediators such as TNFα were identified as triggering active human cytomegalovirus (HCMV) infection. Here, we demonstrate that a highly stressful event in the absence of systemic inflammation, as observed in patients with acute myocardial infarction, leads to the development of an active HCMV infection in latently infected patients. Elucidating the molecular mechanism of virus activation, we could show that catecholamines directly stimulate the HCMV immediate-early (IE) enhancer/promoter in monocytic cells via β-2 adrenergic receptors. Subsequent activation of the cAMP/PK-A-signaling pathway results in enhanced synthesis and binding of the transcription factor CREB-1/ATF-1 to the cAMP-responsive elements within the IE enhancer. Epinephrine also enhanced HCMV gene expression in infected THP-1 cells by about 50% in three of four experiments. These data suggest that HCMV, like HSV-1 and VZV, can be (re)activated under stress conditions.
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