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Titolo:
Suppression of oncogenic viral interferon regulatory factor (vIRF) of Kaposi's sarcoma-associated herpesvirus by ribozyme-mediated cleavage
Autore:
Zhang, YJ; Wang, XP; Deng, JH; Salinas, RA; Oishi, N; Gao, SJ;
Indirizzi:
Univ Texas, Hlth Sci Ctr, Dept Pediat, San Antonio, TX 78229 USA Univ Texas San Antonio TX USA 78229 ept Pediat, San Antonio, TX 78229 USA Univ Texas, Hlth Sci Ctr, Dept Microbiol, San Antonio, TX 78229 USA Univ Texas San Antonio TX USA 78229 Microbiol, San Antonio, TX 78229 USA Canc Therapy & Res Ctr, San Antonio, TX 78229 USA Canc Therapy & Res Ctr San Antonio TX USA 78229 San Antonio, TX 78229 USA
Titolo Testata:
CANCER GENE THERAPY
fascicolo: 4, volume: 8, anno: 2001,
pagine: 285 - 293
SICI:
0929-1903(200104)8:4<285:SOOVIR>2.0.ZU;2-6
Fonte:
ISI
Lingua:
ENG
Soggetto:
RECEPTOR MESSENGER-RNA; GROWTH-FACTOR; RAS RIBOZYME; HAMMERHEAD RIBOZYME; GENE-EXPRESSION; IN-VITRO; C-MYC; INHIBITION; CELLS; HUMAN-HERPESVIRUS-8;
Keywords:
ribozyme; Kaposi's sarcoma-associated herpesvirus; KSHV; oncogene; vIRF;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
31
Recensione:
Indirizzi per estratti:
Indirizzo: Gao, SJ Univ Texas, Hlth Sci Ctr, Dept Pediat, 7703 Floyd Curl Dr, San Antonio, TX78229 USA Univ Texas 7703 Floyd Curl Dr San Antonio TX USA 78229 TX78229 USA
Citazione:
Y.J. Zhang et al., "Suppression of oncogenic viral interferon regulatory factor (vIRF) of Kaposi's sarcoma-associated herpesvirus by ribozyme-mediated cleavage", CANC GENE T, 8(4), 2001, pp. 285-293

Abstract

Kaposi's sarcoma-associated herpesvirus/human herpesvirus 8 (KSHV/HHV8) has been etiologically associated with several malignancies including Kaposi's sarcoma and primary effusion lymphoma. Oncogenic viral interferon regulatory factor (vIRF) encoded by KSHV ORF - K9 is a homologue of cellular interferon regulatory factor (IRF), and has been demonstrated to inhibit type I! II interferon signal transduction and transform NIH3T3 cells through the interactions with IRF-1, IRF-3, and CRP/p300 proteins. To counteract vlRF's pathogenic role, we have developed five ribozymes targeting ORF-K9 mRNA to suppress vIRF expression. The vIRF RNA substrates were cleaved up to 80% ina substrate-specific manner in transcript cleavage assays in vitro. In a transient transfection assay, two of the ribozymes efficiently suppressed the expression of vIRF protein measured by dual-color immunofluorescence assay that simultaneously detects the expression of both vIRF protein and ribozyme. Flow cytometry analysis showed that these ribozymes reduced vIRF expression up to 76%. A mutant ribozyme had no cleavage activity in vitro, but exhibited antisense effect in vivo. These results suggest that the ribozymesmay provide a new approach for functional knockout of vIRF gene, and are potential candidates of antiviral therapy for KSHV- related malignancies.

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Documento generato il 27/01/20 alle ore 01:23:41