Multiple receptor interactions trigger release of membrane and intracellular calcium stores critical for herpes simplex virus entry

Natalia V. Cheshenko, Wen Liu, Lisa M. Satlin, Betsy Herold

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

Herpes simplex viruses (HSV) harness cellular calcium signaling pathways to facilitate viral entry. Confocal microscopy and small interfering RNA (siRNA) were used to identify the source of the calcium and to dissect the requisite viral-cell interactions. Binding of HSV to human epithelial cells induced no calcium response, but shifting the cells to temperatures permissive for penetration triggered increases in plasma membrane calcium followed by a global release of intracellular calcium. Transfection with siRNA targeting the proteoglycan syndecan-2 blocked viral binding and abrogated any calcium response. Transfection with siRNA targeting nectin-1, a glycoprotein D receptor, also prevented both membrane and intracellular calcium responses. In contrast, the membrane response was preserved after transfection with siRNA targeting integrinαv, a novel glycoprotein H receptor. The membrane response, however, was not sufficient for viral entry, which required interactions with integrinαv and release of inositol-triphosphate receptor-dependent intracellular calcium stores. Thus, calcium plays a critical, complex role in HSV entry.

Original languageEnglish (US)
Pages (from-to)3119-3130
Number of pages12
JournalMolecular Biology of the Cell
Volume18
Issue number8
DOIs
StatePublished - Aug 2007
Externally publishedYes

Fingerprint

Virus Internalization
Intracellular Membranes
Simplexvirus
Calcium
Small Interfering RNA
Transfection
Glycoproteins
Syndecan-2
Inositol 1,4,5-Trisphosphate Receptors
Calcium Signaling
Membranes
Proteoglycans
Confocal Microscopy
Cell Communication
Epithelial Cells
Cell Membrane
Temperature

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

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abstract = "Herpes simplex viruses (HSV) harness cellular calcium signaling pathways to facilitate viral entry. Confocal microscopy and small interfering RNA (siRNA) were used to identify the source of the calcium and to dissect the requisite viral-cell interactions. Binding of HSV to human epithelial cells induced no calcium response, but shifting the cells to temperatures permissive for penetration triggered increases in plasma membrane calcium followed by a global release of intracellular calcium. Transfection with siRNA targeting the proteoglycan syndecan-2 blocked viral binding and abrogated any calcium response. Transfection with siRNA targeting nectin-1, a glycoprotein D receptor, also prevented both membrane and intracellular calcium responses. In contrast, the membrane response was preserved after transfection with siRNA targeting integrinαv, a novel glycoprotein H receptor. The membrane response, however, was not sufficient for viral entry, which required interactions with integrinαv and release of inositol-triphosphate receptor-dependent intracellular calcium stores. Thus, calcium plays a critical, complex role in HSV entry.",
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