Proinflammatory cytokines and chemokines - but not interferon-β - produced in response to HSV-2 in primary human genital epithelial cells are associated with viral replication and the presence of the virion host shutoff protein

Am J Reprod Immunol. 2013 Sep;70(3):199-212. doi: 10.1111/aji.12133. Epub 2013 Apr 29.


Problem: It is unknown whether viral replication or viral components that subvert innate responses in other cells, specifically the virion host shutoff (VHS) protein, play a role in determining primary genital epithelial cell (GEC) innate antiviral responses.

Method of study: Cultures of primary female GECs were exposed to wildtype (WT), VHS-deleted (vhsB), or UV-inactivated HSV-2. Antiviral pathway induction was evaluated by measuring nuclear factor-κB (NFκB) translocation by immunofluorescent microscopy. Proinflammatory cytokines, chemokines, and interferon (IFN) were measured by Luminex or ELISA. Biological activity of IFN-β was evaluated via VSV-GFP bioassay, by blocking secreted IFN-β with neutralizing antibodies and by measuring interferon-stimulated genes by RT-PCR.

Results: Proinflammatory cytokines and chemokines were upregulated in primary GECs in response to replication-competent HSV-2, but suppressed in the presence of the VHS protein. In contrast, upregulation of IFN-β depended on viral replication, but was not affected by VHS. However, the IFN-β produced was biologically active and reduced the viral burden.

Conclusion: Viral factors such as replication and the presence of the VHS protein play important roles in regulating innate antiviral responses against HSV-2 from primary GECs.

Keywords: Cytokines; HSV-2; genital epithelial cells; interferon; mucosal immunity; viral immunology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Cells, Cultured
  • Chemokines / biosynthesis
  • Chlorocebus aethiops
  • Cytokines / biosynthesis*
  • Epithelial Cells / immunology*
  • Epithelial Cells / virology*
  • Female
  • Genitalia, Female / cytology*
  • Genitalia, Female / immunology
  • Genitalia, Female / virology
  • Herpes Simplex / immunology*
  • Herpes Simplex / virology
  • Herpesvirus 2, Human / immunology*
  • Herpesvirus 2, Human / physiology
  • Humans
  • Immunity, Innate
  • Inflammation / virology*
  • Interferon-beta / biosynthesis
  • Middle Aged
  • Ribonucleases / metabolism*
  • Up-Regulation
  • Vero Cells
  • Viral Proteins / metabolism*
  • Virus Replication


  • Chemokines
  • Cytokines
  • Viral Proteins
  • virion host shutoff protein, Simplexvirus
  • Interferon-beta
  • Ribonucleases