Herpes simplex virus triggers activation of calcium-signaling pathways

Natalia Cheshenko, Brian Del Rosario, Craig Woda, Daniel Marcellino, Lisa M. Satlin, Betsy C. Herold

Research output: Contribution to journalArticlepeer-review

122 Scopus citations


The cellular pathways required for herpes simplex virus (HSV) invasion have not been defined. To test the hypothesis that HSV entry triggers activation of Ca2+-signaling pathways, the effects on intracellular calcium concentration ([Ca2+]i) after exposure of cells to HSV were examined. Exposure to virus results in a rapid and transient increase in [Ca2+]i. Pretreatment of cells with pharmacological agents that block release of inositol 1,4,5-triphosphate (IP3)-sensitive endoplasmic reticulum stores abrogates the response. Moreover, treatment of cells with these pharmacological agents inhibits HSV infection and prevents focal adhesion kinase (FAK) phosphorylation, which occurs within 5 min after viral infection. Viruses deleted in glycoprotein L or glycoprotein D, which bind but do not penetrate, fail to induce a [Ca 2+]i response or trigger FAK phosphorylation. Together, these results support a model for HSV infection that requires activation of IP3-responsive Ca2+-signaling pathways and that is associated with FAK phosphorylation. Defining the pathway of viral invasion may lead to new targets for anti-viral therapy.

Original languageEnglish
Pages (from-to)283-293
Number of pages11
JournalJournal of Cell Biology
Issue number2
StatePublished - 27 Oct 2003


  • Focal adhesion kinase
  • IP
  • Membrane fusion
  • Tyrosine phosphorylation
  • Viral entry


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