{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T00:17:13Z","timestamp":1793060233940,"version":"4.5.0"},"reference-count":47,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2011,3,15]],"date-time":"2011-03-15T00:00:00Z","timestamp":1300147200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2011,3,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>Kaposi's sarcoma-associated herpesvirus (KSHV) lytic infection increases the expression of viral and human interleukin-6 (vIL-6 and hIL-6, respectively), an important factor for cell growth and pathogenesis. Here, we report genome-wide analysis of viral RNA targets of KSHV ORF57 by a novel UV-cross-linking and immunoprecipitation (CLIP) assay. We identified 11 viral transcripts as putative ORF57 targets and demonstrate that vIL-6 mRNA is an authentic target of ORF57. Disrupting the ORF57 gene in the KSHV genome leads to inefficient expression of vIL-6. With transient transfection, the expression of vIL-6 could be enhanced greatly in the presence of ORF57 in a dose-dependent manner. We found that the open reading frame (ORF) region of vIL-6 RNA contains an MRE (MTA [ORF57]-responsive element) composed of two motifs, MRE-A and MRE-B, and binding of ORF57 to these two motifs stabilizes vIL-6 RNA and promotes vIL-6 translation. We demonstrate that vIL-6 MRE-B bears an miR-1293 binding site and that, mechanistically, ORF57 competes with miR-1293 for the same binding site to interact with vIL-6 RNA, thereby preventing vIL-6 RNA from association with the miR-1293-specified RNA-induced silencing complex (RISC). Consistent with this, ORF57 also interacts with an miR-608 binding site in the hIL-6 ORF and prevents miR-608 repression of hIL-6. Collectively, our results identify a novel function of ORF57 in being responsible for stabilization of viral and human IL-6 RNAs and the corresponding enhancement of RNA translation. In addition, our data provide the first evidence that a tumor virus may use a viral protein to interfere with microRNA (miRNA)-mediated repression of an miRNA target to induce cell proliferation and tumorigenesis during virus infection.<\/jats:p>","DOI":"10.1128\/jvi.02144-10","type":"journal-article","created":{"date-parts":[[2011,1,6]],"date-time":"2011-01-06T03:02:26Z","timestamp":1294282946000},"page":"2620-2630","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":66,"title":["Kaposi's Sarcoma-Associated Herpesvirus ORF57 Promotes Escape of Viral and Human Interleukin-6 from MicroRNA-Mediated Suppression"],"prefix":"10.1128","volume":"85","author":[{"given":"Jeong-Gu","family":"Kang","sequence":"first","affiliation":[{"name":"Tumor Virus RNA Biology Laboratory, HIV and AIDS Malignancy Branch"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Pripuzova","sequence":"additional","affiliation":[{"name":"Tumor Virus RNA Biology Laboratory, HIV and AIDS Malignancy Branch"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladimir","family":"Majerciak","sequence":"additional","affiliation":[{"name":"Tumor Virus RNA Biology Laboratory, HIV and AIDS Malignancy Branch"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Kruhlak","sequence":"additional","affiliation":[{"name":"Experimental Immunology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu-Yun","family":"Le","sequence":"additional","affiliation":[{"name":"Nanobiology Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi-Ming","family":"Zheng","sequence":"additional","affiliation":[{"name":"Tumor Virus RNA Biology Laboratory, HIV and AIDS Malignancy Branch"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V96.4.1599.h8001599_1599_1601"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V97.7.2173"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature07242"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.01.002"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000194"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1074883"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature08170"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-01-0015"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.76.16.8252-8264.2002"},{"key":"e_1_3_3_11_2","first-page":"501","volume":"10","year":"1999","unstructured":"Foussat, A., et al. 1999. 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