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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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