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

J Gen Virol. 2008 Oct;89(Pt 10):2398-2409. doi: 10.1099/vir.0.2008/003129-0.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / metabolism*
  • Dendritic Cells / cytology
  • Dendritic Cells / immunology
  • Dendritic Cells / virology*
  • Herpes Simplex / immunology*
  • Herpes Simplex / transmission*
  • Herpes Simplex / virology
  • Herpesvirus 1, Human / metabolism
  • Herpesvirus 1, Human / pathogenicity*
  • Herpesvirus 1, Human / physiology
  • Herpesvirus 2, Human / metabolism
  • Herpesvirus 2, Human / pathogenicity*
  • Humans
  • Lectins, C-Type / genetics
  • Lectins, C-Type / metabolism*
  • Monocytes / cytology
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism*
  • Receptors, Virus / metabolism
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Viral Envelope Proteins / metabolism


  • Cell Adhesion Molecules
  • DC-specific ICAM-3 grabbing nonintegrin
  • Lectins, C-Type
  • Receptors, Cell Surface
  • Receptors, Virus
  • Recombinant Proteins
  • Viral Envelope Proteins
  • glycoprotein B, Simplexvirus
  • glycoprotein gC, herpes simplex virus type 1