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Journal of Virology, March 2001, p. 2938-2945, Vol. 75, No. 6
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.6.2938-2945.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Internal Ribosome Entry Site Regulates Translation of Kaposi's Sarcoma-Associated Herpesvirus FLICE Inhibitory Protein

Walter Low,1 Mark Harries,1 Hongtao Ye,2 Ming-Qing Du,2 Chris Boshoff,3 and Mary Collins1,*

Windeyer Institute of Medical Sciences, University College London,1 and Department of Histopathology2 and Wolfson Institute for Biomedical Research,3 Royal Free and University College Medical School, London, United Kingdom

Received 26 October 2000/Accepted 15 December 2000

The gammaherpesvirus Kaposi's sarcoma-associated herpesvirus (KSHV) (or human herpesvirus 8) is associated with the endothelial tumor Kaposi's sarcoma (KS) and lymphoproliferative disorders in immunocompromised individuals. Only a small number of viral proteins are expressed in B cells latently infected with KSHV; here we characterize the mechanism of expression of one of these, the viral FLICE inhibitory protein v-FLIP (K13, ORF71). The v-FLIP coding region is present in a bicistronic message, following the v-cyclin coding region. Using both in vitro translation and cell transfection assays, we have identified an internal ribosome entry site (IRES) preceding the v-FLIP start codon and overlapping the v-cyclin (ORF 72) coding region, which allows v-FLIP translation. Using an antibody against v-FLIP we have detected expression of the endogenous protein in latently infected KSHV-positive primary effusion lymphoma (PEL) cell lines. Induction of apoptosis by serum withdrawal from PEL cells results in a relative increase in v-FLIP synthesis, as previously described for some cellular proteins translated from IRES.


* Corresponding author. Mailing address: Windeyer Institute of Medical Sciences, University College London, 46 Cleveland St., London W1P 6DB, United Kingdom. Phone and Fax: 44-207-679-9301. E-mail: mary.collins{at}ucl.ac.uk.


Journal of Virology, March 2001, p. 2938-2945, Vol. 75, No. 6
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.6.2938-2945.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.



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