Kaposi's Sarcoma Associated Herpes Virus (KSHV/HHV-8) Upregulates Angiogenin During Infection of Human Dermal Microvascular Endothelial Cells Which Induces 45SrRNA Synthesis, Anti-apoptosis, Cell Proliferation, Migration and Angiogenesis. Export

@article{citeulike:4087772, abstract = {KSHV is associated with the angioproliferative Kaposi's sarcoma (KS) lesions characterized by spindle shaped endothelial cells, inflammatory cells, cytokines, growth factors and angiogenic factors. De novo KSHV infection of human microvascular dermal endothelial cells (HMVEC-d) results in increased secretion of several growth factors, cytokines, chemokines and angiogenic factors, and the multifunctional angiogenic protein angiogenin is one of them. KS tissue sections were positive for angiogenin highlighting the importance of angiogenin in KS pathogenesis. Examination of KSHV mediated angiogenin upregulation, secretion and potential outcomes revealed that during infection of primary endothelial cells, KSHV induced a time and dose dependent increase in angiogenin gene expression and protein secretion beginning as early as 8 h post infection until 5 days of our observation period. TIVE-LTC cells latently infected with KSHV secreted high levels of angiogenin. Angiogenin was also detected in BCBL-1 cells carrying KSHV in a latent state. Significant induction of angiogenin was observed in cells expressing KSHV ORF 73 (LANA-1; latent) and ORF 74 (lytic) genes alone, and moderate induction was seen with lytic KSHV ORF50 gene. Angiogenin bound to surface actin, internalized in a microtubule independent manner, and translocated into the nucleus and nucleolus of infected cells. In addition, it increased 45SrRNA gene transcription, anti-apoptosis and proliferation of infected cells, and thus demonstrating the multifunctional nature of KSHV induced angiogenin. These activities were dependent on angiogenin nuclear translocation which was inhibited by neomycin. Upregulation of angiogenin led to an increased activation of urokinase plasminogen activator and generation of active plasmin which facilitated the migration of endothelial cells towards chemoattractants including angiogenin, and chemotaxis was prevented by the inhibition of angiogenin nuclear translocation. Treatment of KSHV infected cell supernatants with anti-angiogenin antibodies significantly inhibited endothelial tube formation, and inhibition of nuclear translocation of angiogenin also blocked the expression of KSHV induced VEGF-C. Collectively, these results strongly suggest that by increasing infected endothelial cell 45SrRNA synthesis, proliferation, migration and angiogenesis, KSHV induced angiogenin could be playing a pivotal role in the pathogenesis of KSHV infection including the angioproliferative nature of KS lesions. Our studies suggest that LANA-1 and vGPCR play roles in KSHV induced angiogenesis and the angiogenic potential of vGPCR might be also due its ability to induce angiogenin.}, author = {Sadagopan, Sathish and Sharma-Walia, Neelam and Veettil, Mohanan Valiya V. and Bottero, Virginie and Levine, Rita and Vart, Richard J J. and Chandran, Bala}, citeulike-article-id = {4087772}, citeulike-linkout-0 = {http://dx.doi.org/10.1128/JVI.02052-08}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/19158252}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=19158252}, day = {21}, doi = {10.1128/JVI.02052-08}, issn = {1098-5514}, journal = {Journal of virology}, keywords = {angiogenin, apoptosis, kshv}, month = {January}, posted-at = {2009-02-23 20:43:42}, priority = {0}, title = {Kaposi's Sarcoma Associated Herpes Virus (KSHV/HHV-8) Upregulates Angiogenin During Infection of Human Dermal Microvascular Endothelial Cells Which Induces 45SrRNA Synthesis, Anti-apoptosis, Cell Proliferation, Migration and Angiogenesis.}, url = {http://dx.doi.org/10.1128/JVI.02052-08}, year = {2009} }

TY - JOUR ID - citeulike:4087772 L3 - citeulike-article-id:4087772 N2 - KSHV is associated with the angioproliferative Kaposi's sarcoma (KS) lesions characterized by spindle shaped endothelial cells, inflammatory cells, cytokines, growth factors and angiogenic factors. De novo KSHV infection of human microvascular dermal endothelial cells (HMVEC-d) results in increased secretion of several growth factors, cytokines, chemokines and angiogenic factors, and the multifunctional angiogenic protein angiogenin is one of them. KS tissue sections were positive for angiogenin highlighting the importance of angiogenin in KS pathogenesis. Examination of KSHV mediated angiogenin upregulation, secretion and potential outcomes revealed that during infection of primary endothelial cells, KSHV induced a time and dose dependent increase in angiogenin gene expression and protein secretion beginning as early as 8 h post infection until 5 days of our observation period. TIVE-LTC cells latently infected with KSHV secreted high levels of angiogenin. Angiogenin was also detected in BCBL-1 cells carrying KSHV in a latent state. Significant induction of angiogenin was observed in cells expressing KSHV ORF 73 (LANA-1; latent) and ORF 74 (lytic) genes alone, and moderate induction was seen with lytic KSHV ORF50 gene. Angiogenin bound to surface actin, internalized in a microtubule independent manner, and translocated into the nucleus and nucleolus of infected cells. In addition, it increased 45SrRNA gene transcription, anti-apoptosis and proliferation of infected cells, and thus demonstrating the multifunctional nature of KSHV induced angiogenin. These activities were dependent on angiogenin nuclear translocation which was inhibited by neomycin. Upregulation of angiogenin led to an increased activation of urokinase plasminogen activator and generation of active plasmin which facilitated the migration of endothelial cells towards chemoattractants including angiogenin, and chemotaxis was prevented by the inhibition of angiogenin nuclear translocation. Treatment of KSHV infected cell supernatants with anti-angiogenin antibodies significantly inhibited endothelial tube formation, and inhibition of nuclear translocation of angiogenin also blocked the expression of KSHV induced VEGF-C. Collectively, these results strongly suggest that by increasing infected endothelial cell 45SrRNA synthesis, proliferation, migration and angiogenesis, KSHV induced angiogenin could be playing a pivotal role in the pathogenesis of KSHV infection including the angioproliferative nature of KS lesions. Our studies suggest that LANA-1 and vGPCR play roles in KSHV induced angiogenesis and the angiogenic potential of vGPCR might be also due its ability to induce angiogenin. JF - Journal of virology SN - 1098-5514 TI - Kaposi's Sarcoma Associated Herpes Virus (KSHV/HHV-8) Upregulates Angiogenin During Infection of Human Dermal Microvascular Endothelial Cells Which Induces 45SrRNA Synthesis, Anti-apoptosis, Cell Proliferation, Migration and Angiogenesis. KW - angiogenin KW - apoptosis KW - kshv AU - Sadagopan, Sathish AU - Sharma-Walia, Neelam AU - Veettil, Mohanan Valiya AU - Bottero, Virginie AU - Levine, Rita AU - Vart, Richard J AU - Chandran, Bala PY - 2009/01/21/ UR - http://dx.doi.org/10.1128/JVI.02052-08 ER -