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Tissue factor and glycoprotein c on herpes simplex virus type 1 are protease-activated receptor 2 cofactors that enhance infection

Academic Article
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Overview

authors

  • Sutherland, M. R.
  • Ruf, Wolfram
  • Pryzdial, E. L. G.

publication date

  • April 2012

journal

  • Blood  Journal

abstract

  • The coagulation system provides physiologic host defense, but it can also be exploited by pathogens for infection. On the HSV1 surface, host-cell-derived tissue factor (TF) and virus-encoded glycoprotein C (gC) can stimulate protease activated receptor 1 (PAR1)-enhanced infection by triggering thrombin production. Using novel engineered HSV1 variants deficient in either TF and/or gC, in the present study, we show that activated coagulation factors X (FXa) or VII (FVIIa) directly affect HSV1 infection of human umbilical vein endothelial cells in a manner that is dependent on viral TF and gC. The combination of FXa and FVIIa maximally enhanced infection for TF(+)/gC(+) HSV1 and receptor desensitization and Ab inhibition demonstrated that both proteases act on PAR2. Inhibitory TF Abs showed that the required TF source was viral. Individually, TF or gC partly enhanced the effect of FXa, but not FVIIa, revealing gC as a novel PAR2 cofactor for FVIIa. In sharp contrast, thrombin enhanced infection via PAR1 independently of viral TF and gC. Thrombin combined with FXa/FVIIa enhanced infection, suggesting that PAR1 and PAR2 are independently involved in virus propagation. These results show that HSV1 surface cofactors promote cellular PAR2-mediated infection, indicating a novel mode by which pathogens exploit the initiation phase of the host hemostatic system.

subject areas

  • Antigens, Surface
  • Antigens, Viral
  • Blood Coagulation Factors
  • Cells, Cultured
  • Coenzymes
  • Disease Progression
  • Herpes Simplex
  • Host-Pathogen Interactions
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Receptor, PAR-2
  • Signal Transduction
  • Thromboplastin
  • Viral Envelope Proteins
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Identity

International Standard Serial Number (ISSN)

  • 0006-4971

Digital Object Identifier (DOI)

  • 10.1182/blood-2011-08-376814

PubMed ID

  • 22374699
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Additional Document Info

start page

  • 3638

end page

  • 3645

volume

  • 119

issue

  • 15

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