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Article: β-adrenoreceptors reactivate Kaposi's sarcoma-associated herpesvirus lytic replication via PKA-dependent control of viral RTA

Titleβ-adrenoreceptors reactivate Kaposi's sarcoma-associated herpesvirus lytic replication via PKA-dependent control of viral RTA
Authors
Issue Date2005
Citation
Journal of Virology, 2005, v. 79, n. 21, p. 13538-13547 How to Cite?
AbstractReactivation of Kaposi's sarcoma-associated herpesvirus (KSHV) lytic replication is mediated by the viral RTA transcription factor, but little is known about the physiological processes controlling its expression or activity. Links between autonomic nervous system activity and AIDS-associated Kaposi's sarcoma led us to examine the potential influence of catecholamine neurotransmitters. Physiological concentrations of epinephrine and norepinephrine efficiently reactivated lytic replication of KSHV in latently infected primary effusion lymphoma cells via β-adrenergic activation of the cellular cyclic AMP/protein kinase A (PKA) signaling pathway. Effects were blocked by PKA antagonists and mimicked by pharmacological and physiological PKA activators (prostaglandin E2 and histamine) or overexpression of the PKA catalytic subunit. PKA up-regulated RTA gene expression, enhanced activity of the RTA promoter, and posttranslationally enhanced RTA's trans-activating capacity for its own promoter and heterologous lytic promoters (e.g., the viral PAN gene). Mutation of predicted phosphorylation targets at RTA serines 525 and 526 inhibited PKA-mediated enhancement of RTA irons-activating capacity. Given the high catecholamine levels at sites of KSHV latency such as the vasculature and lymphoid organs, these data suggest that β-adrenergic control of RTA might constitute a significant physiological regulator of KSHV lytic replication. These findings also suggest novel therapeutic strategies for controlling the activity of this oncogenic gammaherpesvirus in vivo. Copyright © 2005, American Society for Microbiology. All Rights Reserved.
Persistent Identifierhttp://hdl.handle.net/10722/285894
ISSN
2019 Impact Factor: 4.501
2015 SCImago Journal Rankings: 3.347
PubMed Central ID

 

DC FieldValueLanguage
dc.contributor.authorChang, Margaret-
dc.contributor.authorBrown, Helen J.-
dc.contributor.authorCollado-Hidalgo, Alicia-
dc.contributor.authorArevalo, Jesusa M.-
dc.contributor.authorGalic, Zoran-
dc.contributor.authorSymensma, Tonia L.-
dc.contributor.authorTanaka, Lena-
dc.contributor.authorDeng, Hongyu-
dc.contributor.authorZack, Jerome A.-
dc.contributor.authorSun, Ren-
dc.contributor.authorCole, Steve W.-
dc.date.accessioned2020-08-18T04:56:55Z-
dc.date.available2020-08-18T04:56:55Z-
dc.date.issued2005-
dc.identifier.citationJournal of Virology, 2005, v. 79, n. 21, p. 13538-13547-
dc.identifier.issn0022-538X-
dc.identifier.urihttp://hdl.handle.net/10722/285894-
dc.description.abstractReactivation of Kaposi's sarcoma-associated herpesvirus (KSHV) lytic replication is mediated by the viral RTA transcription factor, but little is known about the physiological processes controlling its expression or activity. Links between autonomic nervous system activity and AIDS-associated Kaposi's sarcoma led us to examine the potential influence of catecholamine neurotransmitters. Physiological concentrations of epinephrine and norepinephrine efficiently reactivated lytic replication of KSHV in latently infected primary effusion lymphoma cells via β-adrenergic activation of the cellular cyclic AMP/protein kinase A (PKA) signaling pathway. Effects were blocked by PKA antagonists and mimicked by pharmacological and physiological PKA activators (prostaglandin E2 and histamine) or overexpression of the PKA catalytic subunit. PKA up-regulated RTA gene expression, enhanced activity of the RTA promoter, and posttranslationally enhanced RTA's trans-activating capacity for its own promoter and heterologous lytic promoters (e.g., the viral PAN gene). Mutation of predicted phosphorylation targets at RTA serines 525 and 526 inhibited PKA-mediated enhancement of RTA irons-activating capacity. Given the high catecholamine levels at sites of KSHV latency such as the vasculature and lymphoid organs, these data suggest that β-adrenergic control of RTA might constitute a significant physiological regulator of KSHV lytic replication. These findings also suggest novel therapeutic strategies for controlling the activity of this oncogenic gammaherpesvirus in vivo. Copyright © 2005, American Society for Microbiology. All Rights Reserved.-
dc.languageeng-
dc.relation.ispartofJournal of Virology-
dc.titleβ-adrenoreceptors reactivate Kaposi's sarcoma-associated herpesvirus lytic replication via PKA-dependent control of viral RTA-
dc.typeArticle-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1128/JVI.79.21.13538-13547.2005-
dc.identifier.pmid16227274-
dc.identifier.pmcidPMC1262578-
dc.identifier.scopuseid_2-s2.0-27144514347-
dc.identifier.volume79-
dc.identifier.issue21-
dc.identifier.spage13538-
dc.identifier.epage13547-

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