This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Chang, M.
Right arrow Articles by Cole, S. W.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Chang, M.
Right arrow Articles by Cole, S. W.

 Previous Article  |  Next Article 

Journal of Virology, November 2005, p. 13538-13547, Vol. 79, No. 21
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.21.13538-13547.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

ß-Adrenoreceptors Reactivate Kaposi's Sarcoma-Associated Herpesvirus Lytic Replication via PKA-Dependent Control of Viral RTA

Margaret Chang,1 Helen J. Brown,2 Alicia Collado-Hidalgo,3,6 Jesusa M. Arevalo,3 Zoran Galic,3 Tonia L. Symensma,2,4 Lena Tanaka,4 Hongyu Deng,2 Jerome A. Zack,1,3,5 Ren Sun,2,5 and Steve W. Cole3,5,6*

Departments of Microbiology, Immunology and Molecular Genetics,1 Molecular and Medical Pharmacology,2 Medicine, David E. Geffen School of Medicine, University of California, Los Angeles, California,3 Department of Biological Sciences, Mount Saint Mary's College, Los Angeles, California,4 Jonsson Comprehensive Cancer Center, UCLA AIDS Institute, and UCLA Molecular Biology Institute,5 Norman Cousins Center, University of California, Los Angeles, California6

Received 25 April 2005/ Accepted 5 August 2005

Reactivation 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 ß-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 trans-activating capacity. Given the high catecholamine levels at sites of KSHV latency such as the vasculature and lymphoid organs, these data suggest that ß-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.

* Corresponding author. Mailing address: Department of Medicine, Division of Hematology-Oncology, 11-934, Factor Building, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-1678. Phone: 310-267-4243. Fax: 310-206-1318. E-mail: coles{at}ucla.edu.

Journal of Virology, November 2005, p. 13538-13547, Vol. 79, No. 21
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.21.13538-13547.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Work, T. M., Dagenais, J., Balazs, G. H., Schumacher, J., Lewis, T. D., Leong, J.-A. C., Casey, R. N., Casey, J. W. (2009). In vitro biology of fibropapilloma-associated turtle herpesvirus and host cells in Hawaiian green turtles (Chelonia mydas). J. Gen. Virol. 90: 1943-1950 [Abstract] [Full Text]  
  • Izumiya, Y., Izumiya, C., Hsia, D., Ellison, T. J., Luciw, P. A., Kung, H.-J. (2009). NF-{kappa}B Serves as a Cellular Sensor of Kaposi's Sarcoma-Associated Herpesvirus Latency and Negatively Regulates K-Rta by Antagonizing the RBP-J{kappa} Coactivator. J. Virol. 83: 4435-4446 [Abstract] [Full Text]  
  • Arumugaswami, V., Sitapara, R., Hwang, S., Song, M. J., Ho, T. N., Su, N. Q., Sue, E. Y., Kanagavel, V., Xing, F., Zhang, X., Zhao, M., Deng, H., Wu, T.-T., Kanagavel, S., Zhang, L., Dandekar, S., Papp, J., Sun, R. (2009). High-Resolution Functional Profiling of a Gammaherpesvirus RTA Locus in the Context of the Viral Genome. J. Virol. 83: 1811-1822 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»