title: Cell type-dependent retention and transmission of HIV-1 by DC-SIGN.
abstract: DC-SIGN (CD209) is a C-type lectin expressed by several groups of dendritic cells (DC), including those derived from blood monocytes and DC found beneath genital epithelium. DC-SIGN binds the envelope glycoprotein of HIV-1 and facilitates transmission of infectious virus to permissive CD4(+) T cells. We have compared the capacity of DC-SIGN in different cell types to bind, retain and transmit infectious HIV-1 to T cells. The analyzed cells included monocyte-derived DC, and three different DC-SIGN-expressing transfectants termed THP, 293 and HOS. Our results show that DC-SIGN transfectants were able to bind HIV-1 virions comparably to DC. However, only the THP monocytic cell line shared with DC the capacity to retain for several days virus that was infectious for T cells. In both THP-DC-SIGN transfectants and DC, but not in 293 cells, HIV-1 was localized to intracellular compartments that did not double label for endosomal and lysosomal markers or for DC-SIGN itself. Virus remained detectable in these compartments for at least 2 days. Anti-DC-SIGN antibodies blocked the binding and transmission of HIV-1 in DC-SIGN transfectants, as monitored by PCR for HIV LTR/gag and p24 ELISA. However anti-DC-SIGN antibodies did not block virus binding and transmission to T cells as well in DC as in THP-DC-SIGN transfectants. Thus, the function of DC-SIGN in HIV-1 transmission depends on its cellular context, since only DC and the THP monocyte cell line, but not 293 and HOS, are able to use DC-SIGN to retain HIV-1 in a highly infectious state for several days.
authors.affiliation: Laboratory of Cellular Physiology and Immunology, and Chris Browne Center for Immunology and Immune Diseases, Rockefeller University, 1230 York Avenue, New York, NY 10021, USA.
authors.forename: Christine
authors.initials: C
authors.lastname: Trumpfheller
authors.forename: Chae Gyu
authors.initials: CG
authors.lastname: Park
authors.forename: Jennifer
authors.initials: J
authors.lastname: Finke
authors.forename: Ralph M
authors.initials: RM
authors.lastname: Steinman
authors.forename: Angela
authors.initials: A
authors.lastname: Granelli-Piperno
mesh_terms: D015704:CD4 Antigens / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D018946:Chemokine CCL5 / Q000276:immunology; D003713:Dendritic Cells / Q000378:metabolism; D015658:HIV Infections / Q000378:metabolism* / Q000635:transmission; D015497:HIV-1 / Q000378:metabolism*; D006801:Humans; D037181:Lectins, C-Type / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D015704:CD4 Antigens; D015815:Cell Adhesion Molecules; D018946:Chemokine CCL5; D037181:Lectins, C-Type; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin