{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T05:46:07Z","timestamp":1770011167031,"version":"3.49.0"},"reference-count":73,"publisher":"American Society for Microbiology","issue":"14","license":[{"start":{"date-parts":[[2006,7,15]],"date-time":"2006-07-15T00:00:00Z","timestamp":1152921600000},"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":[[2006,7,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>Kaposi's\nsarcoma-associated herpesvirus (KSHV) is the etiologic agent for\nKaposi's sarcoma (KS) and primary effusion lymphoma (PEL). We\npreviously reported that hypoxia activates KSHV lytic replication and\nthat the promoter for open reading frame 34 (ORF34) contains a\nfunctional hypoxia-responsive element (HRE). ORF34 is part of a cluster\nof lytic genes (ORF34-37) that includes ORF36, a phosphotransferase,\nand ORF37, a shutoff exonuclease. Rapid amplification of cDNA ends\nanalysis revealed that they share a common polyadenylation signal but\nhave two start sites. Two transcripts were identified, one 3.4 kb\nencoding ORF35-37, and the other 4.2 kb encoding ORF34 and also having\ncoding potential for ORF35-37. Exposure of PEL cell lines to hypoxia\ninduced messages of lengths consistent with those of these transcripts.\nReporter assays with Hep3B cells showed activation of both transcripts\nby hypoxia. The ORF34-37 promoter region has six consensus HREs.\nSequential deletion, site-directed mutagenesis experiments, and\nNorthern blot analysis of RNA produced by constructs indicated that the\nsecond HRE (HRE-2) plays a critical role in the hypoxic activation of\nboth RNA transcripts. The ORF35-37 transcript was upregulated by\ncotransfected hypoxia-inducible factor (HIF). Electrophoretic mobility\nshift assays demonstrated that HRE-2 and ancillary sequences bind and\ncompete for HIF with hypoxic Hep3B nuclear extract. The activation of\nthis gene cluster by hypoxia may have implications for the pathogenesis\nof PEL and KS. Moreover, the activation of ORF36 by hypoxia might be\nexploited to develop targeted therapy for PEL, which arises in a\nhypoxic environment (pleural\neffusions).<\/jats:p>","DOI":"10.1128\/jvi.00553-06","type":"journal-article","created":{"date-parts":[[2006,6,29]],"date-time":"2006-06-29T02:27:07Z","timestamp":1151548027000},"page":"7037-7051","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":61,"title":["Genetic Organization and Hypoxic Activation of the Kaposi's Sarcoma-Associated Herpesvirus ORF34-37 Gene Cluster"],"prefix":"10.1128","volume":"80","author":[{"given":"Muzammel","family":"Haque","sequence":"first","affiliation":[{"name":"HIV\rand AIDS Malignancy Branch, Center for Cancer Research, National Cancer\rInstitute, National Institutes for Health, Bethesda, Maryland\r20892-1868"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Victoria","family":"Wang","sequence":"additional","affiliation":[{"name":"HIV\rand AIDS Malignancy Branch, Center for Cancer Research, National Cancer\rInstitute, National Institutes for Health, Bethesda, Maryland\r20892-1868"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David A.","family":"Davis","sequence":"additional","affiliation":[{"name":"HIV\rand AIDS Malignancy Branch, Center for Cancer Research, National Cancer\rInstitute, National Institutes for Health, Bethesda, Maryland\r20892-1868"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhi-Ming","family":"Zheng","sequence":"additional","affiliation":[{"name":"HIV\rand AIDS Malignancy Branch, Center for Cancer Research, National Cancer\rInstitute, National Institutes for Health, Bethesda, Maryland\r20892-1868"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"Yarchoan","sequence":"additional","affiliation":[{"name":"HIV\rand AIDS Malignancy Branch, Center for Cancer Research, National Cancer\rInstitute, National Institutes for Health, Bethesda, Maryland\r20892-1868"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V88.7.2648.bloodjournal8872648"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.75.4.1864-1869.2001"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1069825"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.74.21.10187-10193.2000"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.73.6.4786-4793.1999"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199505043321802"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1006\/viro.1998.9316"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.7997879"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1074883"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M002740200"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V97.10.3244"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-01-0015"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.72.10.8309-8315.1998"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.9.4273"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1124\/mi.2.4.229"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0925-4773(97)00674-6"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.16.9.4604"},{"key":"e_1_3_2_19_2","first-page":"1006","volume":"78","year":"1971","unstructured":"Funahashi, A., T. 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