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Related Collections Immunobiology Phagocytes Apoptosis Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 May 2002, Vol. 99, No. 10, pp. 3725-3734 IMMUNOBIOLOGY Epstein-Barr virus inhibits the development of dendritic cells by promoting apoptosis of their monocyte precursors in the presence of granulocyte macrophage-colony-stimulating factor and interleukin-4 LiQi Li, Daorong Liu, Lindsey Hutt-Fletcher, Andrew Morgan, Maria G. Masucci, and Victor Levitsky From the Microbiology and Tumor Biology Center, Karolinska Institutet, Stockholm, Sweden; the School of Biological Sciences, University of Missouri, Kansas City; and the Department of Pathology and Microbiology, School of Medical Sciences, University of Bristol, United Kingdom. Epstein-Barr virus (EBV) is a tumorigenic human herpesvirus that persists for life in healthy immunocompetent carriers. The viral strategies that prevent its clearance and allow reactivation in the face of persistent immunity are not well understood. Here we demonstrate that EBV infection of monocytes inhibits their development into dendritic cells (DCs), leading to an abnormal cellular response to granulocyte macrophage-colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4) and to apoptotic death. This proapoptotic activity was not affected by UV inactivation and was neutralized by EBV antibody-positive human sera, indicating that binding of the virus to monocytes is sufficient to alter their response to the cytokines. Experiments with the relevant blocking antibodies or with mutated EBV strains lacking either the EBV envelope glycoprotein gp42 or gp85 demonstrated that interaction of the trimolecular gp25-gp42-gp85 complex with the monocyte membrane is required for the effect. Our data provide the first evidence that EBV can prevent the development of DCs through a mechanism that appears to bypass the requirement for viral gene expression, and they suggest a new strategy for interference with the function of DCs during the initiation and maintenance of virus-specific immune responses. © 2002 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: C. Le Clorennec, T.-S. Ouk, I. Youlyouz-Marfak, S. Panteix, C.-C. Martin, J. Rastelli, E. Adriaenssens, U. Zimber-Strobl, J. Coll, J. Feuillard, et al. Molecular Basis of Cytotoxicity of Epstein-Barr Virus (EBV) Latent Membrane Protein 1 (LMP1) in EBV Latency III B Cells: LMP1 Induces Type II Ligand-Independent Autoactivation of CD95/Fas with Caspase 8-Mediated Apoptosis J. Virol., July 1, 2008; 82(13): 6721 - 6733. [Abstract] [Full Text] [PDF] R. Hochreiter, C. Ptaschinski, S. L. Kunkel, and R. 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