DC-SIGN mediates cell-free infection and transmission of human T-cell lymphotropic virus type 1 by dendritic cells.
Despite the susceptibility of dendritic cells (DCs) to human T-cell lymphotropic virus type 1 (HTLV-1) infection and the defined role of these cells in disease pathogenesis, the mechanisms of viral binding to DCs have not been fully delineated. Recently, a glucose transporter, GLUT-1, heparan sulfate proteoglycans (HSPGs), and neuropilin-1 (NRP-1) were demonstrated to facilitate HTLV-1 entry into T cells. DCs express their own array of antigen receptors, the most important being the DC-specific intercellular adhesion molecule-3 (ICAM-3)-grabbing nonintegrin (DC-SIGN) with respect to retrovirus binding. Consequently, the role of DC-SIGN and other HTLV-1 attachment factors was analyzed in viral binding, transmission, and productive infection using monocyte-derived DCs (MDDCs), blood myeloid DCs, and B-cell lines expressing DC-SIGN. The relative expression of DC-SIGN, GLUT-1, HSPGs, and NRP-1 first was examined on both DCs and B-cell lines. Although the inhibition of these molecules reduced viral binding, HTLV-1 transmission from DCs to T cells was mediated primarily by DC-SIGN. DC-SIGN also was shown to play a role in the infection of MDDCs as well as model B-cell lines. The HTLV-1 infection of MDDCs also was achieved in blood myeloid DCs following the enhancement of virus-induced interleukin-4 production and subsequent DC-SIGN expression in this cell population. This study represents the first comprehensive analysis of potential HTLV-1 receptors on DCs and strongly suggests that DC-SIGN plays a critical role in HTLV-1 binding, transmission, and infection, thereby providing an attractive target for the development of antiretroviral therapeutics and microbicides.
Jain
Pooja
P
Department of Microbiology and Immunology, Institute of Molecular Medicine and Infectious Disease, Drexel University College of Medicine, New College Building, Rm. 18311, 245 N. 15th St., Philadelphia, PA 19102, USA.
Manuel
Sharrón L
SL
Khan
Zafar K
ZK
Ahuja
Jaya
J
Quann
Kevin
K
Wigdahl
Brian
B
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000276:immunology*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000378:metabolism / Q000821:virology; D015686:Gene Products, env / Q000235:genetics / Q000378:metabolism; D051272:Glucose Transporter Type 1 / Q000235:genetics / Q000378:metabolism; D019812:Heparan Sulfate Proteoglycans / Q000378:metabolism; D015368:Human T-lymphotropic virus 1 / Q000276:immunology / Q000472:pathogenicity; D006801:Humans; D015847:Interleukin-4 / Q000276:immunology; D037181:Lectins, C-Type / Q000235:genetics / Q000276:immunology*; D039942:Neuropilin-1 / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D011956:Receptors, Cell Surface / Q000235:genetics / Q000276:immunology*; D015682:Retroviridae Proteins, Oncogenic / Q000235:genetics / Q000378:metabolism; D053585:Virus Attachment; D053586:Virus Internalization; D014779:Virus Replication; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D015815:Cell Adhesion Molecules; D015686:Gene Products, env; D051272:Glucose Transporter Type 1; D019812:Heparan Sulfate Proteoglycans; D015847:Interleukin-4; D037181:Lectins, C-Type; D039942:Neuropilin-1; D011956:Receptors, Cell Surface; D015682:Retroviridae Proteins, Oncogenic; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C055266:gp46 protein, Human T-cell leukemia virus type I
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