DC-SIGN enhances herpes simplex virus infection of dendritic cells in cis

Dendritic cells (DCs) are essential to 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, which results in latency and recurrent infections. Of the two HSV subtypes described HSV-1 causes mainly oral-facial lesions while 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. Here we demonstrate that both HSV-1 and -2 interact with the DC-specific C-type lectin DCSIGN. Further analyses demonstrate that DC-SIGN interacts with both gB and gC. Binding of HSV-1 to immature DCs depends on both DC-SIGN and heparan sulphate proteoglycans, since blocking antibodies against DC-SIGN and heparinase treatment abrogate HSV-1 interactions. Strikingly, HSV-1 infection of DCs is almost completely inhibited by blocking antibodies against DC-SIGN. Thus, DC-SIGN is an important attachment receptor for HSV-1 on immature DCs that enhances infection of DCs in cis. Our data 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.