Back to Search
Start Over
Kaposi's Sarcoma-Associated Herpesvirus Induces Rapid Release of Angiopoietin-2 from Endothelial Cells
- Source :
- Journal of Virology. 87:6326-6335
- Publication Year :
- 2013
- Publisher :
- American Society for Microbiology, 2013.
-
Abstract
- Kaposi sarcoma-associated herpesvirus (KSHV) stimulates proliferation, angiogenesis, and inflammation to promote Kaposi sarcoma (KS) tumor growth, which involves various growth factors and cytokines. Previously, we found that KSHV infection of human umbilical vein endothelial cells (HUVECs) induces a transcriptional induction of the proangiogenic and proinflammatory cytokine angiopoietin-2 (Ang-2). Here, we report that KSHV induces rapid release of Ang-2 that is presynthesized and stored in the Weibel-Palade bodies (WPB) of endothelial cells upon binding to its integrin receptors. Blocking viral binding to integrins inhibits Ang-2 release. KSHV binding activates the integrin tyrosine kinase receptor signaling pathways, leading to tyrosine phosphorylation of focal adhesion kinase (FAK), the tyrosine kinase Src, and the CalĪ±2 subunit of the l -type calcium channel to trigger rapid calcium (Ca 2+ ) influx. Pretreatment of endothelial cells with specific inhibitors of protein tyrosine kinases inhibits KSHV-induced Ca 2+ influx and Ang-2 release. Inhibition of Ca 2+ mobilization with calcium channel blockers also inhibits Ang-2 release. Thus, the interaction between KSHV and its integrin receptors plays a key role in regulating rapid Ang-2 release from endothelial cells. This finding highlights a novel mechanism of viral induction of angiogenesis and inflammation, which might play important roles in the early event of KS tumor development.
- Subjects :
- biology
Angiogenesis
Immunology
Integrin
Tyrosine phosphorylation
medicine.disease_cause
Microbiology
Receptor tyrosine kinase
chemistry.chemical_compound
chemistry
Virology
Insect Science
biology.protein
medicine
Cancer research
Signal transduction
Kaposi's sarcoma-associated herpesvirus
Tyrosine kinase
Proto-oncogene tyrosine-protein kinase Src
Subjects
Details
- ISSN :
- 10985514 and 0022538X
- Volume :
- 87
- Database :
- OpenAIRE
- Journal :
- Journal of Virology
- Accession number :
- edsair.doi...........851ad1baa3f0a6368baf47d845ffb04c