Journal of General Virology, Vol 80, 83-90, Copyright © 1999 by Society for General Microbiology

ARTICLES

Induction of human herpesvirus-8 DNA replication and transcription by butyrate and TPA in BCBL-1 cells

Y Yu, JB Black, CS Goldsmith, PJ Browning, K Bhalla and MK Offermann
Winship Cancer Center, Emory University, Atlanta, GA 30322, USA.

Human herpesvirus-8 (HHV-8) is a gammaherpesvirus that is present primarily in a state of low level persistence in primary effusion lymphoma cell lines. Using BCBL-1 cells that harbour HHV-8 but lack Epstein-Barr virus, we demonstrate that sodium butyrate is much more effective than the phorbol ester 12-O-tetradecanoyl phorbol-13-acetate (TPA) at inducing high levels of class II and III virus transcription and viral DNA replication, but also initiates apoptosis. Apoptosis occurs prior to assembly of virions when high concentrations of butyrate (1-3 mM) are used, whereas reduction of butyrate concentration to 0.3 mM decreases the rate of apoptosis and results in production and secretion of enveloped virions that are visualized at high number by electron microscopy in approximately 20% of BCBL-1 cells. Butyrate induces much higher levels of multiple class II and class III transcripts than does TPA, including v-MIPI, v-IL-6, v-Bcl-2, vGPCR and ORF26. A decrease in concentration of butyrate from 3 to 0.3 mM delays the peak induction of these genes, but peak levels remain higher than peak levels in response to TPA. These studies indicate that the massive apoptosis induced by 3 mM butyrate could be diminished and delayed by reduction of butyrate concentration to 0.3 mM, thereby allowing expression of high levels of lytic-associated genes and production of high yields of HHV-8 virions.

This article has been cited by other articles:

				T. M. Work, J. Dagenais, G. H. Balazs, J. Schumacher, T. D. Lewis, J.-A. C. Leong, R. N. Casey, and J. W. Casey In vitro biology of fibropapilloma-associated turtle herpesvirus and host cells in Hawaiian green turtles (Chelonia mydas) J. Gen. Virol., August 1, 2009; 90(8): 1943 - 1950. [Abstract] [Full Text] [PDF]

				P.-C. Chang, L. D. Fitzgerald, A. Van Geelen, Y. Izumiya, T. J. Ellison, D.-H. Wang, D. K. Ann, P. A. Luciw, and H.-J. Kung Kruppel-Associated Box Domain-Associated Protein-1 as a Latency Regulator for Kaposi's Sarcoma-Associated Herpesvirus and Its Modulation by the Viral Protein Kinase Cancer Res., July 15, 2009; 69(14): 5681 - 5689. [Abstract] [Full Text] [PDF]

				T. L. Morris, R. R. Arnold, and J. Webster-Cyriaque Signaling Cascades Triggered by Bacterial Metabolic End Products during Reactivation of Kaposi's Sarcoma-Associated Herpesvirus J. Virol., June 1, 2007; 81(11): 6032 - 6042. [Abstract] [Full Text] [PDF]

				N. S. Taus, D. R. Herndon, D. L. Traul, J. P. Stewart, M. Ackermann, H. Li, D. P. Knowles, G. S. Lewis, and K. A. Brayton Comparison of ovine herpesvirus 2 genomes isolated from domestic sheep (Ovis aries) and a clinically affected cow (Bos bovis) J. Gen. Virol., January 1, 2007; 88(1): 40 - 45. [Abstract] [Full Text] [PDF]

				L. A. Adang, C. H. Parsons, and D. H. Kedes Asynchronous Progression through the Lytic Cascade and Variations in Intracellular Viral Loads Revealed by High-Throughput Single-Cell Analysis of Kaposi's Sarcoma-Associated Herpesvirus Infection. J. Virol., October 1, 2006; 80(20): 10073 - 10082. [Abstract] [Full Text] [PDF]

				M. Haque, V. Wang, D. A. Davis, Z.-M. Zheng, and R. Yarchoan Genetic Organization and Hypoxic Activation of the Kaposi's Sarcoma-Associated Herpesvirus ORF34-37 Gene Cluster J. Virol., July 15, 2006; 80(14): 7037 - 7051. [Abstract] [Full Text] [PDF]

				C. M. Gonzalez, E. L. Wong, B. S. Bowser, G. K. Hong, S. Kenney, and B. Damania Identification and Characterization of the Orf49 Protein of Kaposi's Sarcoma-Associated Herpesvirus J. Virol., March 15, 2006; 80(6): 3062 - 3070. [Abstract] [Full Text] [PDF]

				M. Cannon, E. Cesarman, and C. Boshoff KSHV G protein-coupled receptor inhibits lytic gene transcription in primary-effusion lymphoma cells via p21-mediated inhibition of Cdk2 Blood, January 1, 2006; 107(1): 277 - 284. [Abstract] [Full Text] [PDF]

				L. Chen and M. Lagunoff Establishment and Maintenance of Kaposi's Sarcoma-Associated Herpesvirus Latency in B Cells J. Virol., November 15, 2005; 79(22): 14383 - 14391. [Abstract] [Full Text] [PDF]

				S. Matsumura, Y. Fujita, E. Gomez, N. Tanese, and A. C. Wilson Activation of the Kaposi's Sarcoma-Associated Herpesvirus Major Latency Locus by the Lytic Switch Protein RTA (ORF50) J. Virol., July 1, 2005; 79(13): 8493 - 8505. [Abstract] [Full Text] [PDF]

				C. M. Klass, L. T. Krug, V. P. Pozharskaya, and M. K. Offermann The targeting of primary effusion lymphoma cells for apoptosis by inducing lytic replication of human herpesvirus 8 while blocking virus production Blood, May 15, 2005; 105(10): 4028 - 4034. [Abstract] [Full Text] [PDF]

				J. Ye, D. Shedd, and G. Miller An Sp1 Response Element in the Kaposi's Sarcoma-Associated Herpesvirus Open Reading Frame 50 Promoter Mediates Lytic Cycle Induction by Butyrate J. Virol., February 1, 2005; 79(3): 1397 - 1408. [Abstract] [Full Text] [PDF]

				J.-H. Deng, Y.-J. Zhang, X.-P. Wang, and S.-J. Gao Lytic Replication-Defective Kaposi's Sarcoma-Associated Herpesvirus: Potential Role in Infection and Malignant Transformation J. Virol., October 15, 2004; 78(20): 11108 - 11120. [Abstract] [Full Text] [PDF]

				V. P. Pozharskaya, L. L. Weakland, and M. K. Offermann Inhibition of infectious human herpesvirus 8 production by gamma interferon and alpha interferon in BCBL-1 cells J. Gen. Virol., October 1, 2004; 85(10): 2779 - 2787. [Abstract] [Full Text] [PDF]

				M. R. Staudt, Y. Kanan, J. H. Jeong, J. F. Papin, R. Hines-Boykin, and D. P. Dittmer The Tumor Microenvironment Controls Primary Effusion Lymphoma Growth in Vivo Cancer Res., July 15, 2004; 64(14): 4790 - 4799. [Abstract] [Full Text] [PDF]

				V. P. Pozharskaya, L. L. Weakland, J. C. Zimring, L. T. Krug, E. R. Unger, A. Neisch, H. Joshi, N. Inoue, and M. K. Offermann Short Duration of Elevated vIRF-1 Expression during Lytic Replication of Human Herpesvirus 8 Limits Its Ability To Block Antiviral Responses Induced by Alpha Interferon in BCBL-1 Cells J. Virol., June 15, 2004; 78(12): 6621 - 6635. [Abstract] [Full Text] [PDF]

				M. Haque, D. A. Davis, V. Wang, I. Widmer, and R. Yarchoan Kaposi's Sarcoma-Associated Herpesvirus (Human Herpesvirus 8) Contains Hypoxia Response Elements: Relevance to Lytic Induction by Hypoxia J. Virol., June 15, 2003; 77(12): 6761 - 6768. [Abstract] [Full Text] [PDF]

				H. Nakamura, M. Lu, Y. Gwack, J. Souvlis, S. L. Zeichner, and J. U. Jung Global Changes in Kaposi's Sarcoma-Associated Virus Gene Expression Patterns following Expression of a Tetracycline-Inducible Rta Transactivator J. Virol., April 1, 2003; 77(7): 4205 - 4220. [Abstract] [Full Text] [PDF]

				B. J. Dezube, M. Zambela, D. R. Sage, J.-F. Wang, and J. D. Fingeroth Characterization of Kaposi sarcoma-associated herpesvirus/human herpesvirus-8 infection of human vascular endothelial cells: early events Blood, July 18, 2002; 100(3): 888 - 896. [Abstract] [Full Text] [PDF]

				S. Wang, S. Liu, M.-H. Wu, Y. Geng, and C. Wood Identification of a Cellular Protein That Interacts and Synergizes with the RTA (ORF50) Protein of Kaposi's Sarcoma-Associated Herpesvirus in Transcriptional Activation J. Virol., December 15, 2001; 75(24): 11961 - 11973. [Abstract] [Full Text] [PDF]

				C. S. Malone, M. D. Miner, J. R. Doerr, J. P. Jackson, S. E. Jacobsen, R. Wall, and M. Teitell CmC(A/T)GG DNA methylation in mature B cell lymphoma gene silencing PNAS, August 10, 2001; (2001) 181206898. [Abstract] [Full Text] [PDF]

				J. Jeong, J. Papin, and D. Dittmer Differential Regulation of the Overlapping Kaposi's Sarcoma-Associated Herpesvirus vGCR (orf74) and LANA (orf73) Promoters J. Virol., February 15, 2001; 75(4): 1798 - 1807. [Abstract] [Full Text]

				M. Mercader, B. Taddeo, J. R. Panella, B. Chandran, B. J. Nickoloff, and K. E. Foreman Induction of HHV-8 Lytic Cycle Replication by Inflammatory Cytokines Produced by HIV-1-Infected T Cells Am. J. Pathol., June 1, 2000; 156(6): 1961 - 1971. [Abstract] [Full Text] [PDF]

				F. Pica, A. Volpi, A. Serafino, M. Fraschetti, O. Franzese, and E. Garaci Autocrine nerve growth factor is essential for cell survival and viral maturation in HHV-8-infected primary effusion lymphoma cells Blood, May 1, 2000; 95(9): 2905 - 2912. [Abstract] [Full Text] [PDF]

				J. P. Zoeteweij, S. T. Eyes, J. M. Orenstein, T. Kawamura, L. Wu, B. Chandran, B. Forghani, and A. Blauvelt Identification and Rapid Quantification of Early- and Late-Lytic Human Herpesvirus 8 Infection in Single Cells by Flow Cytometric Analysis: Characterization of Antiherpesvirus Agents J. Virol., July 1, 1999; 73(7): 5894 - 5902. [Abstract] [Full Text]

				C. S. Malone, M. D. Miner, J. R. Doerr, J. P. Jackson, S. E. Jacobsen, R. Wall, and M. Teitell CmC(A/T)GG DNA methylation in mature B cell lymphoma gene silencing PNAS, August 28, 2001; 98(18): 10404 - 10409. [Abstract] [Full Text] [PDF]