Angiogenesis in Viral Immunoinflammatory Lesions Barry T. Rouse University of Tennessee Part 2
Which molecules are induced by HSV infection to mediate angiogenesis?
INTRASTROMAL VEGF CAUSES NEOVASCULARIZATION 4 days post admin FITC labelled PECAM 1 monoclonal antibody
VEGF expression after HSV-1 corneal infection VEGF in corneal lysate (pg/ml) Days p.i.
a b c VEGF+ cells in HSV infected corneas Day 1 Day 8 Day 15
Corneal Epithelial Cells VEGF+ GFP-HSV GFP-HSV M J774A.1 Cell Line VEGF production - a paracrine effect
Since VEGF response to HSV is paracrine, how is it induced? • Some cellular or viral protein released from infected cell induces • Viral DNA with PAMP activity
Bioactive DNA • Support: HSV DNA rich in potential bioactive CpGs • Doubts: • Would need to gain access to tissues from producer cells • Unexplored
FITC-CpG stimulates VEGF production in J774A.1 cells Cytoplasm Nuclear Control ODN CpG ODN
CpG ODN VEGF HSV DNA Vehicle Control DNA Control ODN HSV DNA and CpG ODN induce angiogenesis in mouse corneal micropocket assay
HSV DNA induces angiogenesis in mouse corneal micropocket assay 2 1.5 Angiogenic Area (mm2) 1 0.5 0 VEGF 0.5 1 2 5g Sperm Vehicle HSV-DNA DNA
Anti-VEGF suppresses HSV-DNA and CpG induced angiogenesis 1.5 1 Angiogenic Area (mm2) 0.5 0
Conclusion • One mechanism by which the paracrine effect of HSV on VEGF production occurs could involve release of viral DNA
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