• Cytokines;
  • genital epithelial cells;
  • HSV-2;
  • interferon;
  • mucosal immunity;
  • viral immunology


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.


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.


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.