{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T13:31:42Z","timestamp":1770989502071,"version":"3.50.1"},"reference-count":53,"publisher":"American Society for Microbiology","issue":"11","license":[{"start":{"date-parts":[[2013,6,1]],"date-time":"2013-06-01T00:00:00Z","timestamp":1370044800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2013,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            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 Cal\u03b12 subunit of the\n            <jats:sc>l<\/jats:sc>\n            -type calcium channel to trigger rapid calcium (Ca\n            <jats:sup>2+<\/jats:sup>\n            ) influx. Pretreatment of endothelial cells with specific inhibitors of protein tyrosine kinases inhibits KSHV-induced Ca\n            <jats:sup>2+<\/jats:sup>\n            influx and Ang-2 release. Inhibition of Ca\n            <jats:sup>2+<\/jats:sup>\n            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.\n          <\/jats:p>","DOI":"10.1128\/jvi.03303-12","type":"journal-article","created":{"date-parts":[[2013,3,28]],"date-time":"2013-03-28T01:54:33Z","timestamp":1364435673000},"page":"6326-6335","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":19,"title":["Kaposi's Sarcoma-Associated Herpesvirus Induces Rapid Release of Angiopoietin-2 from Endothelial Cells"],"prefix":"10.1128","volume":"87","author":[{"given":"Feng-Chun","family":"Ye","sequence":"first","affiliation":[{"name":"Department of Biological Sciences, School of Dental Medicine, Case Western Reserve University, Cleveland, Ohio, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fu-Chun","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Greehey Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stanley","family":"Nithianantham","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, School of Dental Medicine, Case Western Reserve University, Cleveland, Ohio, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bala","family":"Chandran","sequence":"additional","affiliation":[{"name":"H. 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Bligh Cancer Research Laboratories, Department of Microbiology and Immunology, Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, Illinois, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao-Lan","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, School of Dental Medicine, Case Western Reserve University, Cleveland, Ohio, USA"},{"name":"College of Life Sciences, Hubei University, Wuhan, People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aaron","family":"Weinberg","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, School of Dental Medicine, Case Western Reserve University, Cleveland, Ohio, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shou-Jiang","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Greehey Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA"},{"name":"Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, California, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.7997879"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-8049(01)00121-6"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1615\/CritRevOncog.v9.i2.20"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00873-07"},{"key":"e_1_3_2_6_2","first-page":"4873","article-title":"The Kaposi's sarcoma-associated herpes virus G protein-coupled receptor up-regulates vascular endothelial growth factor expression and secretion through mitogen-activated protein kinase and p38 pathways acting on hypoxia-inducible factor 1alpha","volume":"60","author":"Sodhi A","year":"2000","unstructured":"SodhiA MontanerS PatelV ZoharM BaisC MesriEA GutkindJS. 2000. 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