Journal of General Virology, Vol 80, 75-82, Copyright © 1999 by Society for General Microbiology

ARTICLES

Analysis of murine gammaherpesvirus-68 transcription during lytic and latent infection

JP Simas, D Swann, R Bowden and S Efstathiou
Department of Pathology, University of Cambridge, UK. jps@mole.bio.cam.ac.uk

Murine gammaherpesvirus-68 (MHV-68) is a gamma2-herpesvirus that upon experimental infection of laboratory mice establishes a latent infection in B lymphocytes. To date, no virus-encoded gene products have been reported to be expressed during latent infection. In this study, viral transcription has been analysed in a persistently infected B-cell line and abundant and preferential transcription of open reading frame M3 has been identified. Significantly, in situ hybridization analysis of latently infected mouse spleens with probes corresponding to 20 MHV-68 ORFs demonstrated active transcription of a single ORF, corresponding to M3. The kinetics and pattern of transcription of M3 were compared with that of the virally encoded tRNAs (vtRNAs), previously demonstrated to constitute a marker for latent infection in the spleen. Transcription of vtRNAs in splenic tissue could be first detected at 7 days post-inoculation (p.i.) in scattered cells in periarteriolar lymphoid sheaths (PALS). At 10 days p.i., vtRNA transcription was widespread and localized not only to cells in PALS but also to cells within developing germinal centres and from 21 days p.i. expression was detected exclusively within lymphoid follicles. Transcription of vtRNAs could be detected as late as 70 days p.i. In contrast, the histological localization of M3 transcription, which was first detected at 7 days p.i. in scattered cells in PALS, never changed and transcription could not be detected beyond 21 days p.i. These results suggest that M3 is an ORF that is expressed early during the establishment of latency in vivo.

This article has been cited by other articles:

				S. Hwang, T.-T. Wu, L. M. Tong, K. S. Kim, D. Martinez-Guzman, A. D. Colantonio, C. H. Uittenbogaart, and R. Sun Persistent Gammaherpesvirus Replication and Dynamic Interaction with the Host In Vivo J. Virol., December 15, 2008; 82(24): 12498 - 12509. [Abstract] [Full Text] [PDF]

				H. Li, K. Ikuta, J. W. Sixbey, and S. A. Tibbetts A Replication-Defective Gammaherpesvirus Efficiently Establishes Long-Term Latency in Macrophages but Not in B Cells In Vivo J. Virol., September 1, 2008; 82(17): 8500 - 8508. [Abstract] [Full Text] [PDF]

				V. L. Tarakanova, F. Kreisel, D. W. White, and H. W. Virgin IV Murine Gammaherpesvirus 68 Genes both Induce and Suppress Lymphoproliferative Disease J. Virol., January 15, 2008; 82(2): 1034 - 1039. [Abstract] [Full Text] [PDF]

				K. A. Smith, S. Efstathiou, and A. Cooke Murine Gammaherpesvirus-68 Infection Alters Self-Antigen Presentation and Type 1 Diabetes Onset in NOD Mice J. Immunol., December 1, 2007; 179(11): 7325 - 7333. [Abstract] [Full Text] [PDF]

				L. Rodrigues, M. Pires de Miranda, M. J. Caloca, X. R. Bustelo, and J. P. Simas Activation of Vav by the Gammaherpesvirus M2 Protein Contributes to the Establishment of Viral Latency in B Lymphocytes. J. Virol., June 1, 2006; 80(12): 6123 - 6135. [Abstract] [Full Text] [PDF]

				V. L. Tarakanova, F. Suarez, S. A. Tibbetts, M. A. Jacoby, K. E. Weck, J. L. Hess, S. H. Speck, and H. W. Virgin IV Murine Gammaherpesvirus 68 Infection Is Associated with Lymphoproliferative Disease and Lymphoma in BALB {beta}2 Microglobulin-Deficient Mice J. Virol., December 1, 2005; 79(23): 14668 - 14679. [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]

				J. P. Simas, S. Marques, A. Bridgeman, S. Efstathiou, and H. Adler The M2 gene product of murine gammaherpesvirus 68 is required for efficient colonization of splenic follicles but is not necessary for expansion of latently infected germinal centre B cells J. Gen. Virol., October 1, 2004; 85(10): 2789 - 2797. [Abstract] [Full Text] [PDF]

				A. C. Townsley, B. M. Dutia, and A. A. Nash The M4 Gene of Murine Gammaherpesvirus Modulates Productive and Latent Infection In Vivo J. Virol., January 15, 2004; 78(2): 758 - 767. [Abstract] [Full Text] [PDF]

				P. Fowler, S. Marques, J. P. Simas, and S. Efstathiou ORF73 of murine herpesvirus-68 is critical for the establishment and maintenance of latency J. Gen. Virol., December 1, 2003; 84(12): 3405 - 3416. [Abstract] [Full Text] [PDF]

				N. J. Moorman, D. O. Willer, and S. H. Speck The Gammaherpesvirus 68 Latency-Associated Nuclear Antigen Homolog Is Critical for the Establishment of Splenic Latency J. Virol., October 1, 2003; 77(19): 10295 - 10303. [Abstract] [Full Text] [PDF]

				D. Martinez-Guzman, T. Rickabaugh, T.-T. Wu, H. Brown, S. Cole, M. J. Song, L. Tong, and R. Sun Transcription Program of Murine Gammaherpesvirus 68 J. Virol., October 1, 2003; 77(19): 10488 - 10503. [Abstract] [Full Text] [PDF]

				I.-J. Kim, E. Flano, D. L. Woodland, F. E. Lund, T. D. Randall, and M. A. Blackman Maintenance of Long Term {gamma}-Herpesvirus B Cell Latency Is Dependent on CD40-Mediated Development of Memory B Cells J. Immunol., July 15, 2003; 171(2): 886 - 892. [Abstract] [Full Text] [PDF]

				S. Marques, S. Efstathiou, K. G. Smith, M. Haury, and J. P. Simas Selective Gene Expression of Latent Murine Gammaherpesvirus 68 in B Lymphocytes J. Virol., July 1, 2003; 77(13): 7308 - 7318. [Abstract] [Full Text] [PDF]

				B. J. Lee, U. H. Koszinowski, S. R. Sarawar, and H. Adler A Gammaherpesvirus G Protein-Coupled Receptor Homologue Is Required for Increased Viral Replication in Response to Chemokines and Efficient Reactivation from Latency J. Immunol., January 1, 2003; 170(1): 243 - 251. [Abstract] [Full Text] [PDF]

				E. Flano, I.-J. Kim, D. L. Woodland, and M. A. Blackman {gamma}-Herpesvirus Latency Is Preferentially Maintained in Splenic Germinal Center and Memory B Cells J. Exp. Med., November 18, 2002; 196(10): 1363 - 1372. [Abstract] [Full Text] [PDF]

				S. Gangappa, S. B. Kapadia, S. H. Speck, and H. W. Virgin IV Antibody to a Lytic Cycle Viral Protein Decreases Gammaherpesvirus Latency in B-Cell-Deficient Mice J. Virol., October 17, 2002; 76(22): 11460 - 11468. [Abstract] [Full Text] [PDF]

				B. T. Seet and G. McFadden Viral chemokine-binding proteins J. Leukoc. Biol., July 1, 2002; 72(1): 24 - 34. [Abstract] [Full Text] [PDF]

				E. T. Clambey, H. W. Virgin IV, and S. H. Speck Characterization of a Spontaneous 9.5-Kilobase-Deletion Mutant of Murine Gammaherpesvirus 68 Reveals Tissue-Specific Genetic Requirements for Latency J. Virol., June 5, 2002; 76(13): 6532 - 6544. [Abstract] [Full Text] [PDF]

				J. W. Ahn, K. L. Powell, P. Kellam, and D. G. Alber Gammaherpesvirus Lytic Gene Expression as Characterized by DNA Array J. Virol., May 13, 2002; 76(12): 6244 - 6256. [Abstract] [Full Text] [PDF]

				A. Bridgeman, P. G. Stevenson, J. P. Simas, and S. Efstathiou A Secreted Chemokine Binding Protein Encoded by Murine Gammaherpesvirus-68 Is Necessary for the Establishment of a Normal Latent Load J. Exp. Med., August 6, 2001; 194(3): 301 - 312. [Abstract] [Full Text] [PDF]

				R. Rochford, M. L. Lutzke, R. S. Alfinito, A. Clavo, and R. D. Cardin Kinetics of Murine Gammaherpesvirus 68 Gene Expression following Infection of Murine Cells in Culture and in Mice J. Virol., June 1, 2001; 75(11): 4955 - 4963. [Abstract] [Full Text]

				A. I. Macrae, B. M. Dutia, S. Milligan, D. G. Brownstein, D. J. Allen, J. Mistrikova, A. J. Davison, A. A. Nash, and J. P. Stewart Analysis of a Novel Strain of Murine Gammaherpesvirus Reveals a Genomic Locus Important for Acute Pathogenesis J. Virol., June 1, 2001; 75(11): 5315 - 5327. [Abstract] [Full Text]

				J Nicholas Evolutionary aspects of oncogenic herpesviruses Mol. Pathol., October 1, 2000; 53(5): 222 - 237. [Abstract] [Full Text]

				E. J. Usherwood, D. J. Roy, K. Ward, S. L. Surman, B. M. Dutia, M. A. Blackman, J. P. Stewart, and D. L. Woodland Control of Gammaherpesvirus Latency by Latent Antigen-specific CD8+ T Cells J. Exp. Med., September 25, 2000; 192(7): 943 - 952. [Abstract] [Full Text] [PDF]

				L. F. van Dyk, H. W. Virgin IV, and S. H. Speck The Murine Gammaherpesvirus 68 v-Cyclin Is a Critical Regulator of Reactivation from Latency J. Virol., August 15, 2000; 74(16): 7451 - 7461. [Abstract] [Full Text]

				V. van Berkel, J. Barrett, H. L. Tiffany, D. H. Fremont, P. M. Murphy, G. McFadden, S. H. Speck, and H. W. Virgin IV Identification of a Gammaherpesvirus Selective Chemokine Binding Protein That Inhibits Chemokine Action J. Virol., August 1, 2000; 74(15): 6741 - 6747. [Abstract] [Full Text]

				A. T. Hoge, S. B. Hendrickson, and W. H. Burns Murine Gammaherpesvirus 68 Cyclin D Homologue Is Required for Efficient Reactivation from Latency J. Virol., August 1, 2000; 74(15): 7016 - 7023. [Abstract] [Full Text]

				E. T. Clambey, H. W. Virgin IV, and S. H. Speck Disruption of the Murine Gammaherpesvirus 68 M1 Open Reading Frame Leads to Enhanced Reactivation from Latency J. Virol., February 15, 2000; 74(4): 1973 - 1984. [Abstract] [Full Text]

				C. M. Parry, J. P. Simas, V. P. Smith, C. A. Stewart, A. C. Minson, S. Efstathiou, and A. Alcami A Broad Spectrum Secreted Chemokine Binding Protein Encoded by a Herpesvirus J. Exp. Med., February 7, 2000; 191(3): 573 - 578. [Abstract] [Full Text] [PDF]

				S. B. Kapadia, H. Molina, V. van Berkel, S. H. Speck, and H. W. Virgin IV Murine Gammaherpesvirus 68 Encodes a Functional Regulator of Complement Activation J. Virol., September 1, 1999; 73(9): 7658 - 7670. [Abstract] [Full Text]

				V. van Berkel, K. Preiter, H. W. Virgin IV, and S. H. Speck Identification and Initial Characterization of the Murine Gammaherpesvirus 68 Gene M3, Encoding an Abundantly Secreted Protein J. Virol., May 1, 1999; 73(5): 4524 - 4529. [Abstract] [Full Text]

				S. Gangappa, L. F. van Dyk, T. J. Jewett, S. H. Speck, and H. W. Virgin IV Identification of the In Vivo Role of a Viral bcl-2 J. Exp. Med., April 1, 2002; 195(7): 931 - 940. [Abstract] [Full Text] [PDF]

				M. A. Blackman and E. Flano Persistent {gamma}-herpesvirus Infections: What Can We Learn from an Experimental Mouse Model? J. Exp. Med., April 1, 2002; 195(7): F29 - F32. [Full Text] [PDF]