DC-SIGNR, a DC-SIGN homologue expressed in endothelial cells, binds to human and simian immunodeficiency viruses and activates infection in trans

DC-SIGN, a C-type lectin expressed on the surface of dendritic cells (DCs), efficiently binds and transmits HIVs and simian immunodeficiency viruses to susceptible cells in trans. A DC-SIGN homologue, termed DC-SIGNR, has recently been described. Herein we show that DC-SIGNR, like DC-SIGN, can bind to multiple strains of HIV-1, HIV-2, and simian immunodeficiency virus and transmit these viruses to both T cell lines and human peripheral blood mononuclear cells. Binding of virus to DC-SIGNR was dependent on carbohydrate recognition. Immunostaining with a DC-SIGNR-specific antiserum showed that DC-SIGNR was expressed on sinusoidal endothelial cells in the liver and on endothelial cells in lymph node sinuses and placental villi. The presence of this efficient virus attachment factor on multiple endothelial cell types indicates that DC-SIGNR could play a role in the vertical transmission of primate lentiviruses, in the enabling of HIV to traverse the capillary endothelium in some organs, and in the presentation of virus to CD4-positive cells in multiple locations including lymph nodes.

[1]  M. Malim,et al.  Human Immunodeficiency Virus Type 1 Spinoculation Enhances Infection through Virus Binding , 2000, Journal of Virology.

[2]  R. Doms Beyond receptor expression: the influence of receptor conformation, density, and affinity in HIV-1 infection. , 2000, Virology.

[3]  J. Trowsdale,et al.  Cutting Edge: DC-SIGN; a Related Gene, DC-SIGNR; and CD23 Form a Cluster on 19p131 2 , 2000, The Journal of Immunology.

[4]  D. Kabat,et al.  Cooperation of Multiple CCR5 Coreceptors Is Required for Infections by Human Immunodeficiency Virus Type 1 , 2000, Journal of Virology.

[5]  R. Doms,et al.  Expression and coreceptor activity of STRL33/Bonzo on primary peripheral blood lymphocytes. , 2000, Blood.

[6]  Guido Gerken,et al.  Local control of the immune response in the liver , 2000, Immunological reviews.

[7]  M. Bergeron,et al.  Interaction between virion-bound host intercellular adhesion molecule-1 and the high-affinity state of lymphocyte function-associated antigen-1 on target cells renders R5 and X4 isolates of human immunodeficiency virus type 1 more refractory to neutralization. , 2000, Virology.

[8]  Douglas S Kwon,et al.  DC-SIGN, a Dendritic Cell–Specific HIV-1-Binding Protein that Enhances trans-Infection of T Cells , 2000, Cell.

[9]  C. Figdor,et al.  Identification of DC-SIGN, a Novel Dendritic Cell–Specific ICAM-3 Receptor that Supports Primary Immune Responses , 2000, Cell.

[10]  R. Steinman DC-SIGN A Guide to Some Mysteries of Dendritic Cells , 2000, Cell.

[11]  R. Steinman,et al.  Rapid infection of oral mucosal-associated lymphoid tissue with simian immunodeficiency virus. , 1999, Science.

[12]  S. Camus,et al.  The susceptibility to X4 and R5 human immunodeficiency virus-1 strains of dendritic cells derived in vitro from CD34(+) hematopoietic progenitor cells is primarily determined by their maturation stage. , 1999, Blood.

[13]  M. L. Penn,et al.  A trans-receptor mechanism for infection of CD4-negative cells by human immunodeficiency virus type 1 , 1999, Current Biology.

[14]  Q. Sattentau,et al.  HIV-1 attachment: another look. , 1999, Trends in microbiology.

[15]  G. Gerken,et al.  Endotoxin down-regulates T cell activation by antigen-presenting liver sinusoidal endothelial cells. , 1999, Journal of immunology.

[16]  M. Newell Mechanisms and timing of mother‐to‐child transmission of HIV‐1 , 1998, AIDS.

[17]  Q. Sattentau,et al.  Human Immunodeficiency Virus Type 1 Attachment to HeLa CD4 Cells Is CD4 Independent and gp120 Dependent and Requires Cell Surface Heparans , 1998, Journal of Virology.

[18]  B. Chesebro,et al.  Effects of CCR5 and CD4 Cell Surface Concentrations on Infections by Macrophagetropic Isolates of Human Immunodeficiency Virus Type 1 , 1998, Journal of Virology.

[19]  R. Steinman,et al.  Immature Dendritic Cells Selectively Replicate Macrophagetropic (M-Tropic) Human Immunodeficiency Virus Type 1, while Mature Cells Efficiently Transmit both M- and T-Tropic Virus to T Cells , 1998, Journal of Virology.

[20]  B. Korber,et al.  A new classification for HIV-1 , 1998, Nature.

[21]  Q. Sattentau,et al.  Inhibition of Virus Attachment to CD4+ Target Cells Is a Major Mechanism of T Cell Line–adapted HIV-1 Neutralization , 1997, The Journal of experimental medicine.

[22]  J. Hoxie,et al.  Human immunodeficiency virus-1 entry into purified blood dendritic cells through CC and CXC chemokine coreceptors. , 1997, Blood.

[23]  Simon C Watkins,et al.  In vivo migration of dendritic cells differentiated in vitro: a chimpanzee model. , 1997, Journal of immunology.

[24]  Anthony S. Fauci,et al.  Host factors and the pathogenesis of HIV-induced disease , 1996, Nature.

[25]  Marc Parmentier,et al.  A Dual-Tropic Primary HIV-1 Isolate That Uses Fusin and the β-Chemokine Receptors CKR-5, CKR-3, and CKR-2b as Fusion Cofactors , 1996, Cell.

[26]  Ying Sun,et al.  The β-Chemokine Receptors CCR3 and CCR5 Facilitate Infection by Primary HIV-1 Isolates , 1996, Cell.

[27]  C. Broder,et al.  CC CKR5: A RANTES, MIP-1α, MIP-1ॆ Receptor as a Fusion Cofactor for Macrophage-Tropic HIV-1 , 1996, Science.

[28]  Virginia Litwin,et al.  HIV-1 entry into CD4+ cells is mediated by the chemokine receptor CC-CKR-5 , 1996, Nature.

[29]  Stephen C. Peiper,et al.  Identification of a major co-receptor for primary isolates of HIV-1 , 1996, Nature.

[30]  Paul E. Kennedy,et al.  HIV-1 Entry Cofactor: Functional cDNA Cloning of a Seven-Transmembrane, G Protein-Coupled Receptor , 1996, Science.

[31]  D. Weissman,et al.  Three populations of cells with dendritic morphology exist in peripheral blood, only one of which is infectable with human immunodeficiency virus type 1. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[32]  K Inaba,et al.  Dendritic cells exposed to human immunodeficiency virus type-1 transmit a vigorous cytopathic infection to CD4+ T cells. , 1992, Science.

[33]  D. Jaeck,et al.  Primary cultures of endothelial cells from the human liver sinusoid are permissive for human immunodeficiency virus type 1. , 1992, Proceedings of the National Academy of Sciences of the United States of America.