Internal ribosome entry site regulates translation of Kaposi's sarcoma-associated herpesvirus FLICE inhibitory protein.
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.
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Windeyer Institute of Medical Sciences, University College London, United Kingdom.
Harries
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Ye
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Du
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Boshoff
C
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Collins
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D020121:5' Untranslated Regions; D000818:Animals; D001402:B-Lymphocytes; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; D002352:Carrier Proteins / Q000096:biosynthesis*; D002461:Cell Line, Transformed; D002472:Cell Transformation, Viral; D016213:Cyclins; D015967:Gene Expression Regulation, Viral; D019288:Herpesvirus 8, Human / Q000472:pathogenicity* / Q000502:physiology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D014176:Protein Biosynthesis; D012270:Ribosomes / Q000378:metabolism*; D014162:Transfection; D014764:Viral Proteins / Q000096:biosynthesis* / Q000235:genetics
D020121:5' Untranslated Regions; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; C506386:CFLAR protein, human; D002352:Carrier Proteins; D016213:Cyclins; D047908:Intracellular Signaling Peptides and Proteins; D014764:Viral Proteins