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 Coleman, H. M.
Right arrow Articles by Stevenson, P. G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Coleman, H. M.
Right arrow Articles by Stevenson, P. G.

 Previous Article  |  Next Article 

Journal of Virology, December 2003, p. 13093-13105, Vol. 77, No. 24
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.24.13093-13105.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

An Internal Ribosome Entry Site Directs Translation of the Murine Gammaherpesvirus 68 MK3 Open Reading Frame

Heather M. Coleman, Ian Brierley, and Philip G. Stevenson*

Division of Virology, Department of Pathology, University of Cambridge, Cambridge CB2 1QP, United Kingdom

Received 22 May 2003/ Accepted 12 September 2003

The gammaherpesviruses characteristically drive the proliferation of latently infected lymphocytes. The murine gammaherpesvirus 68 (MHV-68) MK3 protein contributes to this process in vivo by evading CD8+-T-cell recognition during latency, as well as during lytic infection. We analyzed some of the molecular mechanisms that control MK3 expression. No dedicated MK3 mRNA was detected. Instead, the MK3 open reading frame (ORF) was transcribed as part of a bicistronic mRNA, downstream of a previously unidentified ORF, 13M. The 13M/MK3 promoter appeared to extend approximately 1 kb 5' of the transcription start site and included elements both dependent on and independent of the ORF50 lytic transactivator. MK3 was translated from the bicistronic transcript by virtue of an internal ribosome entry site (IRES) element. RNA structure mapping identified two stem-loops between 13M and MK3 that were sufficient for IRES activity in a bicistronic reporter plasmid and a third stem-loop just within the MK3 coding sequence, with a subtler, perhaps regulatory role. Overall, translation of the MHV-68 MK3 bore a striking resemblance to that of the Kaposi's sarcoma-associated herpesvirus vFLIP, suggesting that IRES elements are a common theme of latent gammaherpesvirus immune evasion in proliferating cells.

* Corresponding author. Mailing address: Division of Virology, Department of Pathology, University of Cambridge, Tennis Court Rd., Cambridge CB2 1QP, United Kingdom. Phone: 44-1223-336921. Fax: 44-1223-336926. E-mail: pgs27{at}mole.bio.cam.ac.uk.

Journal of Virology, December 2003, p. 13093-13105, Vol. 77, No. 24
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.24.13093-13105.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Stevenson, P. G., Simas, J. P., Efstathiou, S. (2009). Immune control of mammalian gamma-herpesviruses: lessons from murid herpesvirus-4. J. Gen. Virol. 90: 2317-2330 [Abstract] [Full Text]  
  • Kupresanin, F., Chow, J., Mount, A., Smith, C. M., Stevenson, P. G., Belz, G. T. (2007). Dendritic Cells Present Lytic Antigens and Maintain Function throughout Persistent {gamma}-Herpesvirus Infection. J. Immunol. 179: 7506-7513 [Abstract] [Full Text]  
  • Adler, H., Steer, B., Freimuller, K., Haas, J. (2007). Murine Gammaherpesvirus 68 Contains Two Functional Lytic Origins of Replication. J. Virol. 81: 7300-7305 [Abstract] [Full Text]  
  • Griffiths, A., Coen, D. M. (2005). An unusual internal ribosome entry site in the herpes simplex virus thymidine kinase gene. Proc. Natl. Acad. Sci. USA 102: 9667-9672 [Abstract] [Full Text]  
  • Coleman, H. M., Efstathiou, S., Stevenson, P. G. (2005). Transcription of the murine gammaherpesvirus 68 ORF73 from promoters in the viral terminal repeats. J. Gen. Virol. 86: 561-574 [Abstract] [Full Text]  
  • Jacobs, J. L., Dinman, J. D. (2004). Systematic analysis of bicistronic reporter assay data. Nucleic Acids Res 32: e160-e160 [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»