Background DNA fragments that appeared to belong to an unidentifiedhuman herpesvirus were recently found in more than 90 percentof Kaposi's sarcoma lesions associated with the acquired immunodeficiencysyndrome (AIDS). These fragments were also found in 6 of 39tissue samples without Kaposi's sarcoma, including 3 malignantlymphomas, from patients with AIDS, but not in samples frompatients without AIDS.
Methods We examined the DNA of 193 lymphomas from 42 patientswith AIDS and 151 patients who did not have AIDS. We searchedthe DNA for sequences of Kaposi's sarcoma–associated herpesvirus(KSHV) by Southern blot hybridization, the polymerase chainreaction (PCR), or both. The PCR products in the positive sampleswere sequenced and compared with the KSHV sequences in Kaposi'ssarcoma tissues from patients with AIDS.
Results KSHV sequences were identified in eight lymphomas inpatients infected with the human immunodeficiency virus. Alleight, and only these eight, were body-cavity–based lymphomas— that is, they were characterized by pleural, pericardial,or peritoneal lymphomatous effusions. All eight lymphomas alsocontained the Epstein–Barr viral genome. KSHV sequenceswere not found in the other 185 lymphomas. KSHV sequences were40 to 80 times more abundant in the body-cavity–basedlymphomas than in the Kaposi's sarcoma lesions. A high degreeof conservation of KSHV sequences in Kaposi's sarcoma and inthe eight lymphomas suggests the presence of the same agentin both lesions.
Conclusions The recently discovered KSHV DNA sequences occurin an unusual subgroup of AIDS-related B-cell lymphomas, butnot in any other lymphoid neoplasm studied thus far. Our findingstrongly suggests that a novel herpesvirus has a pathogenicrole in AIDS-related body-cavity–based lymphomas.
Source Information
From the Department of Pathology, The New York Hospital–Cornell Medical Center, New York (E.C., D.M.K.); the Department of Pathology (Y.C.) and the Division of Epidemiology (P.S.M.), School of Public Health, Columbia University, New York; and the Division of Anatomic Pathology, Department of Pathology and Laboratory Medicine, Cedars–Sinai Medical Center, Los Angeles (J.W.S.).
Address reprint requests to Dr. Cesarman at The New York Hospital–Cornell Medical Center, Department of Pathology, 525 E. 68th St., New York, NY 10021.
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[Abstract][Full Text]
Ottinger, M., Christalla, T., Nathan, K., Brinkmann, M. M., Viejo-Borbolla, A., Schulz, T. F.
(2006). Kaposi's Sarcoma-Associated Herpesvirus LANA-1 Interacts with the Short Variant of BRD4 and Releases Cells from a BRD4- and BRD2/RING3-Induced G1 Cell Cycle Arrest. J. Virol.
80: 10772-10786
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Carroll, P. A., Kenerson, H. L., Yeung, R. S., Lagunoff, M.
(2006). Latent Kaposi's Sarcoma-Associated Herpesvirus Infection of Endothelial Cells Activates Hypoxia-Induced Factors. J. Virol.
80: 10802-10812
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Inoue, S, Miyamoto, T, Yoshino, T, Yamadori, I, Hagari, Y, Yamamoto, O
(2006). Primary effusion lymphoma with skin involvement.. J. Clin. Pathol.
59: 1221-1222
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Arumugaswami, V., Wu, T.-T., Martinez-Guzman, D., Jia, Q., Deng, H., Reyes, N., Sun, R.
(2006). ORF18 Is a Transfactor That Is Essential for Late Gene Transcription of a Gammaherpesvirus. J. Virol.
80: 9730-9740
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Chen, D., Nicholas, J.
(2006). Structural Requirements for gp80 Independence of Human Herpesvirus 8 Interleukin-6 (vIL-6) and Evidence for gp80 Stabilization of gp130 Signaling Complexes Induced by vIL-6. J. Virol.
80: 9811-9821
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Kovaleva, M., Bussmeyer, I., Rabe, B., Grotzinger, J., Sudarman, E., Eichler, J., Conrad, U., Rose-John, S., Scheller, J.
(2006). Abrogation of Viral Interleukin-6 (vIL-6)-Induced Signaling by Intracellular Retention and Neutralization of vIL-6 with an Anti-vIL-6 Single-Chain Antibody Selected by Phage Display. J. Virol.
80: 8510-8520
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Haque, M., Wang, V., Davis, D. A., Zheng, Z.-M., Yarchoan, R.
(2006). Genetic Organization and Hypoxic Activation of the Kaposi's Sarcoma-Associated Herpesvirus ORF34-37 Gene Cluster. J. Virol.
80: 7037-7051
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Lan, K., Choudhuri, T., Murakami, M., Kuppers, D. A., Robertson, E. S.
(2006). Intracellular Activated Notch1 Is Critical for Proliferation of Kaposi's Sarcoma-Associated Herpesvirus-Associated B-Lymphoma Cell Lines In Vitro. J. Virol.
80: 6411-6419
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Sharma-Walia, N., Raghu, H., Sadagopan, S., Sivakumar, R., Veettil, M. V., Naranatt, P. P., Smith, M. M., Chandran, B.
(2006). Cyclooxygenase 2 Induced by Kaposi's Sarcoma-Associated Herpesvirus Early during In Vitro Infection of Target Cells Plays a Role in the Maintenance of Latent Viral Gene Expression. J. Virol.
80: 6534-6552
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Lu, F., Day, L., Gao, S.-J., Lieberman, P. M.
(2006). Acetylation of the Latency-Associated Nuclear Antigen Regulates Repression of Kaposi's Sarcoma-Associated Herpesvirus Lytic Transcription. J. Virol.
80: 5273-5282
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Speciale, L., Biffi, R., Mancuso, R., Borghi, E., Mazziotti, R., Ferrante, P.
(2006). Big Endothelin-1 and Interleukin-6 Modulation in Human Microvascular Endothelial Cells After Human Herpesvirus 8 Infection. Exp Biol Med
231: 1171-1175
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Arguello, M., Paz, S., Hernandez, E., Corriveau-Bourque, C., Fawaz, L. M., Hiscott, J., Lin, R.
(2006). Leukotriene A4 Hydrolase Expression in PEL Cells Is Regulated at the Transcriptional Level and Leads to Increased Leukotriene B4 Production.. J. Immunol.
176: 7051-7061
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An, F.-Q., Folarin, H. M., Compitello, N., Roth, J., Gerson, S. L., McCrae, K. R., Fakhari, F. D., Dittmer, D. P., Renne, R.
(2006). Long-Term-Infected Telomerase-Immortalized Endothelial Cells: a Model for Kaposi's Sarcoma-Associated Herpesvirus Latency In Vitro and In Vivo. J. Virol.
80: 4833-4846
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Verma, S. C., Lan, K., Choudhuri, T., Robertson, E. S.
(2006). Kaposi's Sarcoma-Associated Herpesvirus-Encoded Latency-Associated Nuclear Antigen Modulates K1 Expression through Its cis-Acting Elements within the Terminal Repeats. J. Virol.
80: 3445-3458
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Bilello, J. P., Lang, S. M., Wang, F., Aster, J. C., Desrosiers, R. C.
(2006). Infection and Persistence of Rhesus Monkey Rhadinovirus in Immortalized B-Cell Lines. J. Virol.
80: 3644-3649
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Wang, L., Dittmer, D. P., Tomlinson, C. C., Fakhari, F. D., Damania, B.
(2006). Immortalization of Primary Endothelial Cells by the K1 Protein of Kaposi's Sarcoma-Associated Herpesvirus.. Cancer Res.
66: 3658-3666
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Gonzalez, C. M., Wong, E. L., Bowser, B. S., Hong, G. K., Kenney, S., Damania, B.
(2006). Identification and Characterization of the Orf49 Protein of Kaposi's Sarcoma-Associated Herpesvirus. J. Virol.
80: 3062-3070
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