The Journal of Experimental Medicine
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Published 7 April 2003. doi:10.1084/jem.20021840
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© Rockefeller University Press, 0022-1007/2003/4/823 $5.00
The Journal of Experimental Medicine, Volume 197, Number 7, 823-829

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

Boonrat Tassaneetrithep1,6, Timothy H. Burgess2, Angela Granelli-Piperno3, Christine Trumpfheller3, Jennifer Finke3, Wellington Sun4, Michael A. Eller1, Kovit Pattanapanyasat5, Suttipant Sarasombath6, Deborah L. Birx1, Ralph M. Steinman3, Sarah Schlesinger3 and Mary A. Marovich1

1 Division of Retrovirology, Walter Reed Army Institute of Research and Henry M. Jackson Foundation for the Advancement of Military Medicine Diseases, Rockville, MD 20850
2 Viral Diseases Department, Naval Medical Research Center, Silver Spring, MD 20889
3 Laboratory of Cellular Physiology and Immunology, The Rockefeller University, New York, NY 10021
4 Department of Virus Diseases, Walter Reed Army Institute of Research, Silver Spring, MD 20889
5 Division of Instruments for Research, Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
6 Department of Immunology, Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand

Address correspondence to Mary A. Marovich, 13 Taft Ct., Suite 200, Rockville, MD 20850. Phone: 301 251-8337; Fax: 301 762-4177; E-mail: mmarovich{at}hivresearch.org

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.

Key Words: receptor • flavivirus • lectin • antigen-presenting cells • virus receptor


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