{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T10:19:54Z","timestamp":1758709194779},"reference-count":89,"publisher":"American Society for Microbiology","issue":"19","license":[{"start":{"date-parts":[[2001,10,1]],"date-time":"2001-10-01T00:00:00Z","timestamp":1001894400000},"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":[[2001,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            The latency-associated nuclear antigen (LANA) encoded by the Kaposi's sarcoma-associated herpesvirus (KSHV) is expressed in the majority of KSHV-infected cells and in cells coinfected with Epstein-Barr virus (EBV). In coinfected body cavity-based lymphomas (BCBLs), EBV latent membrane protein 1 (LMP1), which is essential for B-lymphocyte transformation, is expressed. EBNA2 upregulates the expression of\n            <jats:italic>LMP1<\/jats:italic>\n            and other cellular genes through specific interactions with cellular transcription factors tethering EBNA2 to its responsive promoters. In coinfected BCBL cells, EBNA2 is not detected but LANA, which is constitutively expressed, contains motifs suggestive of potential transcriptional activity. Additionally, recent studies have shown that LANA is capable of activating cellular promoters. Therefore, we investigated whether LANA can affect transcription from two major EBV latent promoters. In this study, we demonstrated that LANA can efficiently transactivate both the LMP1 and C promoters in the human B-cell line BJAB as well as in the human embryonic kidney 293 cell line. Moreover, we demonstrated that specific domains of LANA containing the putative leucine zipper and the glutamic acid-rich region are highly effective in upregulating these viral promoters, while the amino-terminal region (435 amino acids) exhibited little or no transactivation activity in our assays. We also specifically tested truncations of the LMP1 promoter element and showed that the \u2212204 to +40 region had increased levels of activation compared with a larger region, \u2212512 to +40, which contains two recombination signal-binding protein J\u03ba binding sites. The smaller, \u2212204 to +40 promoter region contains specific binding sites for the Ets family transcription factor PU.1, transcription activating factor\/cyclic AMP response element, and Sp1, all of which are known to function as activators of transcription. Our data therefore suggest a potential role for LANA in regulation of the major EBV latent promoters in KSHV- and EBV-coinfected cells. Furthermore, LANA may be able to activate transcription of viral and cellular promoters in the absence of EBNA2, potentially through association with transcription factors bound to their cognate sequences within the \u2212204 to +40 region. This regulation of viral gene expression is critical for persistence of these DNA tumor viruses and most likely involved in mediating the oncogenic process in these coinfected cells.\n          <\/jats:p>","DOI":"10.1128\/jvi.75.19.9446-9457.2001","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T10:06:37Z","timestamp":1027764397000},"page":"9446-9457","update-policy":"http:\/\/dx.doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":46,"title":["The Latency-Associated Nuclear Antigen Encoded by Kaposi's Sarcoma-Associated Herpesvirus Activates Two Major Essential Epstein-Barr Virus Latent Promoters"],"prefix":"10.1128","volume":"75","author":[{"given":"Angela K.","family":"Groves","sequence":"first","affiliation":[{"name":"<!--label omitted: 1-->Medical Scientist Training Program, Cell and Molecular Biology Graduate Program, Department of Microbiology and Immunology, and Comprehensive Cancer and Geriatrics Center, University of Michigan Medical Center, Ann Arbor, Michigan 48109-0934"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Murray A.","family":"Cotter","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Medical Scientist Training Program, Cell and Molecular Biology Graduate Program, Department of Microbiology and Immunology, and Comprehensive Cancer and Geriatrics Center, University of Michigan Medical Center, Ann Arbor, Michigan 48109-0934"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chitra","family":"Subramanian","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Medical Scientist Training Program, Cell and Molecular Biology Graduate Program, Department of Microbiology and Immunology, and Comprehensive Cancer and Geriatrics Center, University of Michigan Medical Center, Ann Arbor, Michigan 48109-0934"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erle S.","family":"Robertson","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Medical Scientist Training Program, Cell and Molecular Biology Graduate Program, Department of Microbiology and Immunology, and Comprehensive Cancer and Geriatrics Center, University of Michigan Medical Center, Ann Arbor, Michigan 48109-0934"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/17.21.6394"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.284.5414.641"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/91.16.1376"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V91.6.1858"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1006\/viro.1999.9876"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2141.1996.d01-1826.x"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199505043321802"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V86.7.2708.2708"},{"key":"e_1_3_2_10_2","first-page":"53","article-title":"Kaposi's sarcoma-associated herpesvirus in non-AIDS-related lymphomas occurring in body cavities","volume":"149","author":"Cesarman E.","year":"1996","unstructured":"Cesarman E. 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