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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.



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