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Dendritic cells mediate herpes simplex virus infection and transmission through the C-type lectin DC-SIGN

Marein A. W. P. de Jong^1,

Lot de Witte^1,

¹ Department of Molecular Cell Biology and Immunology, VU University Medical Center Amsterdam, van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands
² Department of Clinical Virology, University of Göteborg, Guldhedsgatan 10B, S-413 46 Göteborg, Sweden

Correspondence
Teunis B. H. Geijtenbeek
t.geijtenbeek{at}vumc.nl

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.

These authors contributed equally to this work.