DC-SIGN (CD209) Mediates Dengue Virus Infection of Human Dendritic Cells

  • Boonrat Tassaneetrithep
    1Division of Retrovirology, Walter Reed Army Institute of Research and Henry M. Jackson Foundation for the Advancement of Military Medicine Diseases, Rockville, MD 20850
  • Timothy H. Burgess
    2Viral Diseases Department, Naval Medical Research Center, Silver Spring, MD 20889
  • Angela Granelli-Piperno
    3Laboratory of Cellular Physiology and Immunology, The Rockefeller University, New York, NY 10021
  • Christine Trumpfheller
    3Laboratory of Cellular Physiology and Immunology, The Rockefeller University, New York, NY 10021
  • Jennifer Finke
    3Laboratory of Cellular Physiology and Immunology, The Rockefeller University, New York, NY 10021
  • Wellington Sun
    4Department of Virus Diseases, Walter Reed Army Institute of Research, Silver Spring, MD 20889
  • Michael A. Eller
    1Division of Retrovirology, Walter Reed Army Institute of Research and Henry M. Jackson Foundation for the Advancement of Military Medicine Diseases, Rockville, MD 20850
  • Kovit Pattanapanyasat
    5Division of Instruments for Research, Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
  • Suttipant Sarasombath
    6Department of Immunology, Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
  • Deborah L. Birx
    1Division of Retrovirology, Walter Reed Army Institute of Research and Henry M. Jackson Foundation for the Advancement of Military Medicine Diseases, Rockville, MD 20850
  • Ralph M. Steinman
    3Laboratory of Cellular Physiology and Immunology, The Rockefeller University, New York, NY 10021
  • Sarah Schlesinger
    3Laboratory of Cellular Physiology and Immunology, The Rockefeller University, New York, NY 10021
  • Mary A. Marovich
    1Division of Retrovirology, Walter Reed Army Institute of Research and Henry M. Jackson Foundation for the Advancement of Military Medicine Diseases, Rockville, MD 20850

Abstract

<jats:p>Dengue virus is a single-stranded, enveloped RNA virus that productively infects human dendritic cells (DCs) primarily at the immature stage of their differentiation. We now find that all four serotypes of dengue use DC-SIGN (CD209), a C-type lectin, to infect dendritic cells. THP-1 cells become susceptible to dengue infection after transfection of DC-specific ICAM-3 grabbing nonintegrin (DC-SIGN), or its homologue L-SIGN, whereas the infection of dendritic cells is blocked by anti–DC-SIGN antibodies and not by antibodies to other molecules on these cells. Viruses produced by dendritic cells are infectious for DC-SIGN– and L-SIGN–bearing THP-1 cells and other permissive cell lines. Therefore, DC-SIGN may be considered as a new target for designing therapies that block dengue infection.</jats:p>

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