Dendritic cells mediate herpes simplex virus infection and transmission through the C-type lectin DC-SIGN.
Dendritic cells (DCs) are essential for the induction of specific immune responses against invading pathogens. Herpes simplex virus (HSV) is a common human pathogen that causes painful but mild infections of the skin and mucosa, and which results in latency and recurrent infections. Of the two HSV subtypes described, HSV-1 causes mainly oral-facial lesions, whilst HSV-2 is associated with genital herpes. DCs are involved in HSV-induced immune suppression, but little is known about the molecular interactions between DCs and HSV. This study demonstrated that HSV-1 and -2 both interact with the DC-specific C-type lectin DC-SIGN. Further analyses demonstrated that DC-SIGN interacts with the HSV glycoproteins gB and gC. Binding of HSV-1 to immature DCs depended on both DC-SIGN and heparan sulfate proteoglycans. Strikingly, HSV-1 infection of DCs was almost completely inhibited by blocking antibodies against DC-SIGN. Thus, DC-SIGN is an important attachment receptor for HSV-1 on immature DCs and enhances infection of DCs in cis. In addition, DC-SIGN captures HSV-1 for transmission to permissive target cells. These data strongly suggest that DC-SIGN is a potential target to prevent HSV infection and virus dissemination. Further studies will show whether these interactions are involved in HSV-induced immune suppression.
de Jong
Marein A W P
MAWP
Department of Molecular Cell Biology and Immunology, VU University Medical Center Amsterdam, van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands.
de Witte
Lot
L
Department of Molecular Cell Biology and Immunology, VU University Medical Center Amsterdam, van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands.
Bolmstedt
Anders
A
Department of Clinical Virology, University of Göteborg, Guldhedsgatan 10B, S-413 46 Göteborg, Sweden.
van Kooyk
Yvette
Y
Department of Molecular Cell Biology and Immunology, VU University Medical Center Amsterdam, van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands.
Geijtenbeek
Teunis B H
TBH
Department of Molecular Cell Biology and Immunology, VU University Medical Center Amsterdam, van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands.
D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology / Q000821:virology*; D006561:Herpes Simplex / Q000276:immunology* / Q000635:transmission* / Q000821:virology; D018259:Herpesvirus 1, Human / Q000378:metabolism / Q000472:pathogenicity* / Q000502:physiology; D018258:Herpesvirus 2, Human / Q000378:metabolism / Q000472:pathogenicity*; D006801:Humans; D037181:Lectins, C-Type / Q000235:genetics / Q000378:metabolism*; D009000:Monocytes / Q000166:cytology; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D011991:Receptors, Virus / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D014759:Viral Envelope Proteins / Q000378:metabolism; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D015815:Cell Adhesion Molecules; D037181:Lectins, C-Type; D011956:Receptors, Cell Surface; D011991:Receptors, Virus; D011994:Recombinant Proteins; D014759:Viral Envelope Proteins; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C040495:glycoprotein B, Simplexvirus; C038535:glycoprotein gC, herpes simplex virus type 1