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Blood, 1 December 2005, Vol. 106, No. 12, pp. 3797-3802. Prepublished online as a Blood First Edition Paper on August 9, 2005; DOI 10.1182/blood-2005-04-1627. This Article Full Text (PDF) All Versions of this Article: 2005-04-1627v1 106/12/3797    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 Corte-Real, S. Articles by Goncalves, J. Search for Related Content PubMed PubMed Citation Articles by Corte-Real, S. Articles by Goncalves, J. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted April 21, 2005 Accepted July 28, 2005 Intrabodies targeting the Kaposi's sarcoma-associated herpesvirus latency antigen inhibit viral persistence in lymphoma cells Sofia Corte-Real, Chris Collins, Frederico Aires da Silva, Pedro Silmas, Carlos Barbas III, Yuan Chang, Patrick Moore, and Joao Goncalves* URIA-Centro de Patogenese Molecular, Faculty of Pharmacy, University of Lisbon, Lisbon, Portugal Molecular Virology Program, Hillman Cancer Research Centre, University of Pittsburgh, Pittsburgh, PA, USA Laboratorio de Microbiologia e Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa e Instituto Gulbenkian de Ciencia, Lisbon, Portugal Department of Molecular Biology and Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California, USA * Corresponding author; email: joao.goncalves{at}ff.ul.pt. Kaposi's sarcoma associated herpesvirus (KSHV) latency associated nuclear antigen (LANA1) is essential for the maintenance and segregation of viral episomes in KSHV latently infected B cells. We report development of intracellular, rabbit-derived antibodies generated by phage display technology, which bind to N-terminal LANA1 epitopes and neutralize the chromosome-binding activity of LANA1. Although these cloned single-chain variable domain fragments (scFv) fragments show relatively low binding affinities for the LANA1 viral antigen in in vitro assays, they nonetheless outcompete KSHV-seropositive human sera for LANA1 epitope binding. In heterologous cells, intracellular intrabody expression inhibits LANA1-dependent plasmid maintenance of both an artificial plasmid containing KSHV LANA1 binding sequences and a bacterial artificial chromosome containing the entire KSHV genome. In KSHV naturally infected primary effusion lymphoma cells, intracellular intrabody expression causes a reduction or loss of the typical LANA1 punctuate, nuclear pattern. This morphologically apparent LANA1 dispersion correlates to loss of viral episome by molecular analysis. These data suggest a novel approach to anti-herpes viral therapy and confirms LANA1 is critical target for neutralization of KSHV viral latency. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: H. J. Kwun, S. R. da Silva, I. M. Shah, N. Blake, P. S. Moore, and Y. Chang Kaposi's Sarcoma-Associated Herpesvirus Latency-Associated Nuclear Antigen 1 Mimics Epstein-Barr Virus EBNA1 Immune Evasion through Central Repeat Domain Effects on Protein Processing J. Virol., August 1, 2007; 81(15): 8225 - 8235. [Abstract] [Full Text] [PDF] T. K. Nun, D. J. Kroll, N. H. Oberlies, D. D. Soejarto, R. J. Case, P. Piskaut, T. Matainaho, C. Hilscher, L. Wang, D. P. Dittmer, et al. Development of a fluorescence-based assay to screen antiviral drugs against Kaposi's sarcoma associated herpesvirus Mol. Cancer Ther., August 1, 2007; 6(8): 2360 - 2370. [Abstract] [Full Text] [PDF] M. Kovaleva, I. Bussmeyer, B. Rabe, J. Grotzinger, E. Sudarman, J. Eichler, U. Conrad, S. Rose-John, and J. Scheller 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., September 1, 2006; 80(17): 8510 - 8520. [Abstract] [Full Text] [PDF]

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