Herpes simplex virus triggers activation of calcium-signaling pathways

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

Research output: Contribution to journalArticle

93 Citations (Scopus)

Abstract

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 (US)
Pages (from-to)283-293
Number of pages11
JournalJournal of Cell Biology
Volume163
Issue number2
DOIs
StatePublished - Oct 27 2003
Externally publishedYes

Fingerprint

Virus Activation
Calcium Signaling
Simplexvirus
Focal Adhesion Protein-Tyrosine Kinases
Virus Diseases
Phosphorylation
Glycoproteins
Pharmacology
Viruses
Virus Internalization
Inositol 1,4,5-Trisphosphate
Endoplasmic Reticulum
Calcium

Keywords

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

ASJC Scopus subject areas

  • Cell Biology

Cite this

Herpes simplex virus triggers activation of calcium-signaling pathways. / Cheshenko, Natalia V.; Del Rosario, Brian; Woda, Craig; Marcellino, Daniel; Satlin, Lisa M.; Herold, Betsy.

In: Journal of Cell Biology, Vol. 163, No. 2, 27.10.2003, p. 283-293.

Research output: Contribution to journalArticle

Cheshenko, Natalia V. ; Del Rosario, Brian ; Woda, Craig ; Marcellino, Daniel ; Satlin, Lisa M. ; Herold, Betsy. / Herpes simplex virus triggers activation of calcium-signaling pathways. In: Journal of Cell Biology. 2003 ; Vol. 163, No. 2. pp. 283-293.
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