DC-SIGN facilitates fusion of dendritic cells with human T-cell leukemia virus type 1-infected cells.
Interactions between the oncogenic retrovirus human T-cell leukemia virus type 1 (HTLV-1) and dendritic cells (DCs) are poorly characterized. We show here that monocyte-derived DCs form syncytia and are infected upon coculture with HTLV-1-infected lymphocytes. We examined the role of DC-specific ICAM-3-grabbing nonintegrin (DC-SIGN), a C-type lectin expressed in DCs, in HTLV-1-induced syncytium formation. DC-SIGN is known to bind with high affinity to various viral envelope glycoproteins, including human immunodeficiency virus (HIV) and hepatitis C virus, as well as to the cellular receptors ICAM-2 and ICAM-3. After cocultivating DCs and HTLV-1-infected cells, we found that anti-DC-SIGN monoclonal antibodies (MAbs) were able to decrease the number and size of HTLV-1-induced syncytia. Moreover, expression of the lectin in epithelial-cell lines dramatically enhanced the ability to fuse with HTLV-1-positive cells. Interestingly, in contrast to the envelope (Env) glycoproteins of HIV and other viruses, that of HTLV-1 does not bind directly to DC-SIGN. The facilitating role of the lectin in HTLV-1 syncytium formation is mediated by its interaction with ICAM-2 and ICAM-3, as demonstrated by use of MAbs directed against these adhesion molecules. Altogether, our results indicate that DC-SIGN facilitates HTLV-1 infection and fusion of DCs through an ICAM-dependent mechanism.
Ceccaldi
Pierre-Emmanuel
PE
Unité Epidémiologie et Physiopathologie des Virus Oncogènes, Institut Pasteur, Paris Cedex 15, France.
Delebecque
Frédéric
F
Prevost
Marie-Christine
MC
Moris
Arnaud
A
Abastado
Jean-Pierre
JP
Gessain
Antoine
A
Schwartz
Olivier
O
Ozden
Simona
S
D015815:Cell Adhesion Molecules / Q000378:metabolism / Q000502:physiology*; D002459:Cell Fusion; D002460:Cell Line; D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000502:physiology*; D015686:Gene Products, env / Q000378:metabolism; D015726:Giant Cells / Q000502:physiology / Q000821:virology; D006367:HeLa Cells; D015368:Human T-lymphotropic virus 1 / Q000502:physiology* / Q000648:ultrastructure; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology / Q000378:metabolism; D037181:Lectins, C-Type / Q000378:metabolism / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000378:metabolism / Q000502:physiology*; D013601:T-Lymphocytes / Q000502:physiology* / Q000821:virology*; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D015815:Cell Adhesion Molecules; D015686:Gene Products, env; D018799:Intercellular Adhesion Molecule-1; D037181:Lectins, C-Type; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin