| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
1 Division of Virology, Institute of Biomedical and Life Sciences, University of Glasgow, Church Street, Glasgow G11 5JR, UK
2 Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, USA
Correspondence
J. Barklie Clements
b.clements{at}vir.gla.ac.uk
Kaposi's sarcoma (KS)-associated herpesvirus (KSHV) proteins ORF57 (also known as MTA) and ORF50 (also known as RTA) act post-transcriptionally and transcriptionally to regulate viral lytic gene expression and synergistically activate certain early and late KSHV promoters. When ORF57 and ORF50 were co-expressed, they co-operatively stimulated expression from the promoter of the immediate-early ORF50 gene itself. Co-immunoprecipitations with extracts of KSHV-infected cells showed that ORF57 and ORF50 proteins were present in the same complex. Using the pull-down assay with extracts of KSHV-infected cells, ORF50 protein was shown to interact with a glutathione S-transferase–ORF57 fusion protein. A chromatin immunoprecipitation assay showed that ORF50 promoter sequences were preferentially associated with immunoprecipitated chromatin using both anti-ORF50 and anti-ORF57 antibodies consistent with both an in vivo physical association between ORF57 and ORF50 and a potential role for ORF57 at the transcriptional level. This is the first demonstration of an interaction between these two lytic regulatory proteins in a gammaherpesvirus. Expression of ORF50 protein is sufficient to induce lytic replication in latently infected cells and may determine viral host range, spread and KS pathogenesis in vivo. A new insight into the co-ordinated activities of these two key regulatory proteins is provided in which upregulation of the ORF50 promoter with augmentation of ORF50 activity by ORF57 protein, and vice versa, would facilitate the cascade of lytic viral gene expression, thereby breaking latency. A functional and physical interaction between these two gammaherpesvirus regulatory protein counterparts could be a general feature of the herpesviruses.
This article has been cited by other articles:
|
|
 |
|
  T. Kato-Noah, Y. Xu, C. C. Rossetto, K. Colletti, I. Papouskova, and G. S. Pari Overexpression of the Kaposi's Sarcoma-Associated Herpesvirus Transactivator K-Rta Can Complement a K-bZIP Deletion BACmid and Yields an Enhanced Growth Phenotype J. Virol., December 15, 2007; 81(24): 13519 - 13532. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Palmeri, S. Spadavecchia, K. D. Carroll, and D. M. Lukac Promoter- and Cell-Specific Transcriptional Transactivation by the Kaposi's Sarcoma-Associated Herpesvirus ORF57/Mta Protein J. Virol., December 15, 2007; 81(24): 13299 - 13314. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Nekorchuk, Z. Han, T.-T. Hsieh, and S. Swaminathan Kaposi's Sarcoma-Associated Herpesvirus ORF57 Protein Enhances mRNA Accumulation Independently of Effects on Nuclear RNA Export J. Virol., September 15, 2007; 81(18): 9990 - 9998. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Majerciak, K. Yamanegi, and Z.-M. Zheng Gene Structure and Expression of Kaposi's Sarcoma-Associated Herpesvirus ORF56, ORF57, ORF58, and ORF59 J. Virol., December 15, 2006; 80(24): 11968 - 11981. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Han and S. Swaminathan Kaposi's Sarcoma-Associated Herpesvirus Lytic Gene ORF57 Is Essential for Infectious Virion Production. J. Virol., June 1, 2006; 80(11): 5251 - 5260. [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]
|
|
|
|
|
|
Y. Xu, D. P. AuCoin, A. R. Huete, S. A. Cei, L. J. Hanson, and G. S. Pari A Kaposi's Sarcoma-Associated Herpesvirus/Human Herpesvirus 8 ORF50 Deletion Mutant Is Defective for Reactivation of Latent Virus and DNA Replication J. Virol., March 15, 2005; 79(6): 3479 - 3487. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Malik and J. B. Clements Protein kinase CK2 phosphorylation regulates the interaction of Kaposi's sarcoma-associated herpesvirus regulatory protein ORF57 with its multifunctional partner hnRNP K Nucleic Acids Res., October 14, 2004; 32(18): 5553 - 5569. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| INT J SYST EVOL MICROBIOL | MICROBIOLOGY | J GEN VIROL |
| J MED MICROBIOL | ALL SGM JOURNALS | |
