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Blood, 1 January 2008, Vol. 111, No. 1, pp. 320-327. Prepublished online as a Blood First Edition Paper on September 21, 2007; DOI 10.1182/blood-2007-05-092288. This Article Full Text (PDF) All Versions of this Article: blood-2007-05-092288v1 111/1/320    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Wies, E. Articles by Neipel, F. Search for Related Content PubMed PubMed Citation Articles by Wies, E. Articles by Neipel, F. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted May 29, 2007 Accepted September 13, 2007 The viral interferon regulatory factor-3 is required for the survival of KSHV-infected primary effusion lymphoma cells Effi Wies, Yasuko Mori, Alexander Hahn, Elisabeth Kremmer, Michael Sturzl, Bernhard Fleckenstein, and Frank Neipel* Institut fur Klinische und Molekulare Virologie, Universitat Erlangen-Nurnberg, Erlangen, Germany Laboratory of Virology and Vaccinology, Division of Biomedical Research, National Institute of Biomedical Innovation, Osaka, Japan Institut fur Molekulare Immunologie, GSF, Munchen, Germany Abteilung fur Molekulare und Experimentelle Chirurgie, Chirurgische Klinik, Universitat Erlangen-Nurnberg, Erlangen, Germany * Corresponding author; email: frank.neipel{at}viro.med.uni-erlangen.de. Human herpesvirus-8 (HHV-8), also termed Kaposi's sarcoma associated herpesvirus (KSHV), is etiologically linked to primary effusion lymphoma (PEL). At least ten KSHV-encoded proteins with potential roles in KSHV-associated neoplasia have been identified. However, with few exceptions these putative oncogenes were analyzed in heterologous systems only using over-expression of single genes. Thus, the pathogenetic relevance of most of these putative oncogenes remains essentially unclear. We used RNA interference (RNAi) to knock-down the expression of several KSHV genes in cultured PEL cells carrying the KSHV genome. The viral interferon-regulatory factor 3 (vIRF-3) was found to be required for proliferation and survival of cultured PEL cells. Knock-down of vIRF-3 expression by various RNAi approaches unequivocally resulted in reduced proliferation and increased activity of caspases 3 and/or 7. Thus, vIRF-3 can be seen as a bona fide oncogene of KSHV-associated lymphoma. Surprisingly, although the related Epstein-Barr virus is usually sufficient to immortalize human B-lymphocytes, silencing of vIRF-3 reduced the viability of both EBV-negative and EBV-positive PEL cells. This suggests that KSHV is the driving force in the pathogenesis of primary effusion lymphoma. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: L. Marcos-Villar, F. Lopitz-Otsoa, P. Gallego, C. Munoz-Fontela, J. Gonzalez-Santamaria, M. Campagna, G. Shou-Jiang, M. S. Rodriguez, and C. Rivas Kaposi's Sarcoma-Associated Herpesvirus Protein LANA2 Disrupts PML Oncogenic Domains and Inhibits PML-Mediated Transcriptional Repression of the Survivin Gene J. Virol., September 1, 2009; 83(17): 8849 - 8858. [Abstract] [Full Text] [PDF] E. Wies, A. S. Hahn, K. Schmidt, C. Viebahn, N. Rohland, A. Lux, T. Schellhorn, A. Holzer, J. U. Jung, and F. Neipel The Kaposi's Sarcoma-associated Herpesvirus-encoded vIRF-3 Inhibits Cellular IRF-5 J. Biol. Chem., March 27, 2009; 284(13): 8525 - 8538. [Abstract] [Full Text] [PDF] A. Konrad, E. Wies, M. Thurau, G. Marquardt, E. Naschberger, S. Hentschel, R. Jochmann, T. F. Schulz, H. Erfle, B. Brors, et al. A Systems Biology Approach To Identify the Combination Effects of Human Herpesvirus 8 Genes on NF-{kappa}B Activation J. Virol., March 15, 2009; 83(6): 2563 - 2574. [Abstract] [Full Text] [PDF] A. Carbone, E. Cesarman, M. Spina, A. Gloghini, and T. F. Schulz HIV-associated lymphomas and gamma-herpesviruses Blood, February 5, 2009; 113(6): 1213 - 1224. [Abstract] [Full Text] [PDF] A. A. Mack and B. Sugden EBV Is Necessary for Proliferation of Dually Infected Primary Effusion Lymphoma Cells Cancer Res., September 1, 2008; 68(17): 6963 - 6968. [Abstract] [Full Text] [PDF] R. Subramanian, O. D'Auvergne, H. Kong, and K. G. Kousoulas The Cytoplasmic Terminus of Kaposi's Sarcoma-Associated Herpesvirus Glycoprotein B Is Not Essential for Virion Egress and Infectivity J. Virol., July 15, 2008; 82(14): 7144 - 7154. [Abstract] [Full Text] [PDF]

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