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Blood, 15 February 2007, Vol. 109, No. 4, pp. 1550-1558. Prepublished online as a Blood First Edition Paper on October 17, 2006; DOI 10.1182/blood-2006-05-024034. This Article Full Text Full Text (PDF) Supplemental Tables All Versions of this Article: blood-2006-05-024034v1 109/4/1550    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map 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 Lagos, D. Articles by Boshoff, C. Search for Related Content PubMed PubMed Citation Articles by Lagos, D. Articles by Boshoff, C. Related Collections Hemostasis, Thrombosis, and Vascular Biology Immunobiology Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Kaposi sarcoma herpesvirus–encoded vFLIP and vIRF1 regulate antigen presentation in lymphatic endothelial cells Dimitrios Lagos1, Matthew W. B. Trotter1, Richard J. Vart1, Hsei-Wei Wang1, Nick C. Matthews2, Amy Hansen1, Ornella Flore3, Frances Gotch2, and Chris Boshoff1 1 Cancer Research United Kingdom Viral Oncology Group, Wolfson Institute for Biomedical Research, University College London, London, United Kingdom; 2 Department of Immunology, Imperial College, London, United Kingdom; and 3 Department of Microbiology and Department of Dermatology, New York University School of Medicine, New York, NY Kaposi sarcoma–associated herpesvirus (KSHV) is etiologically linked to Kaposi sarcoma (KS), a tumor genetically akin to lymphatic endothelial cells (LECs). We obtained the immune transcriptional signature of KS and used KSHV-infected LECs (KLECs) as an in vitro model to determine the effects of KSHV on transcription and expression of genes involved in immunity. The antigen presentation, interferon (IFN) response, and cytokine transcriptomes of KLECs resemble those of KS. Transcription of genes involved in class I presentation is increased in KS and after infection of LECs, but MHC-I and ICAM-1 surface expression are down-regulated in KLECs. Inhibition of IFN induction of MHC-I transcription indicates that KSHV regulates MHC-I transcription. We show that MHC-I transcription is regulated by the KSHV-encoded viral FLICE inhibitory protein (vFLIP) and by viral IFN regulatory factor 1 (vIRF1). vFLIP up-regulates MHC-I and ICAM-1 through activation of NF-B and stimulates T-cell proliferation, revealing a mechanism to prevent uncontrolled viral dissemination. In contrast, vIRF1 inhibits basal and IFN- and vFLIP-induced MHC-I transcription and surface expression through its interaction with the transcriptional coactivator p300, contributing to immune evasion. We propose that regulation of MHC-I by vFLIP and vIRF1 plays a crucial role in the host-pathogen equilibrium. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: T.-S. Huang, J.-Y. Hsieh, Y.-H. Wu, C.-H. Jen, Y.-H. Tsuang, S.-H. Chiou, J. Partanen, H. Anderson, T. Jaatinen, Y.-H. Yu, et al. Functional Network Reconstruction Reveals Somatic Stemness Genetic Maps and Dedifferentiation-Like Transcriptome Reprogramming Induced by GATA2 Stem Cells, May 1, 2008; 26(5): 1186 - 1201. [Abstract] [Full Text] [PDF] H. P. Moll, H. Freudenthaler, A. Zommer, E. Buchberger, and C. Brostjan Neutralizing Type I IFN Antibodies Trigger an IFN-Like Response in Endothelial Cells J. Immunol., April 15, 2008; 180(8): 5250 - 5256. [Abstract] [Full Text] [PDF] R. J. Vart, L. L. Nikitenko, D. Lagos, M. W.B. Trotter, M. Cannon, D. Bourboulia, F. Gratrix, Y. Takeuchi, and C. Boshoff Kaposi's Sarcoma-Associated Herpesvirus-Encoded Interleukin-6 and G-Protein-Coupled Receptor Regulate Angiopoietin-2 Expression in Lymphatic Endothelial Cells Cancer Res., May 1, 2007; 67(9): 4042 - 4051. [Abstract] [Full Text] [PDF]

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