Focal adhesion kinase plays a pivotal role in herpes simplex virus entry

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

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

Development of strategies to prevent herpes simplex virus (HSV) infection requires knowledge of cellular pathways harnessed by the virus for invasion. This study demonstrates that HSV induces rapid phosphorylation of focal adhesion kinase (FAK) in several human target cells and that phosphorylation is important for entry post-binding. Nuclear transport of the viral tegument protein VP16, transport of viral capsids to the nuclear pore, and downstream events (including expression of immediate-early genes and viral plaque formation) were substantially reduced in cells transfected with dominant-negative mutants of FAK or small interfering RNA designed to inhibit FAK expression. These observations were substantiated using mouse embryonic fibroblast cells derived from embryonic FAK-deficient mice. Infection was reduced by >90% in knockout cells relative to control cells and was further reduced if the knockout cells were transfected with small interfering RNA targeting proline-rich tyrosine kinase-2, which was also phosphorylated in response to HSV. The knockout cells were permissive for viral binding, and virus triggered an intracellular calcium response, but nuclear transport was inhibited. Together, these results support a novel model for invasion that implicates FAK phosphorylation as important for delivery of viral capsids to the nuclear pore.

Original languageEnglish (US)
Pages (from-to)31116-31125
Number of pages10
JournalJournal of Biological Chemistry
Volume280
Issue number35
DOIs
StatePublished - Sep 2 2005
Externally publishedYes

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Focal Adhesion Protein-Tyrosine Kinases
Virus Internalization
Simplexvirus
Viruses
Phosphorylation
Nuclear Pore
Small Interfering RNA
Cell Nucleus Active Transport
Herpes Simplex Virus Protein Vmw65
Capsid
Focal Adhesion Kinase 2
Fibroblasts
Virus Attachment
Immediate-Early Genes
Genes
Viral Proteins
Protein Transport
Virus Diseases
Cells
Calcium

ASJC Scopus subject areas

  • Biochemistry

Cite this

Focal adhesion kinase plays a pivotal role in herpes simplex virus entry. / Cheshenko, Natalia V.; Liu, Wen; Satlin, Lisa M.; Herold, Betsy.

In: Journal of Biological Chemistry, Vol. 280, No. 35, 02.09.2005, p. 31116-31125.

Research output: Contribution to journalArticle

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