title: Latent KSHV infection of endothelial cells induces integrin beta3 to activate angiogenic phenotypes.
abstract: Kaposi's Sarcoma (KS), the most common tumor of AIDS patients, is a highly vascularized tumor supporting large amounts of angiogenesis. The main cell type of KS tumors is the spindle cell, a cell of endothelial origin, the primary cell type involved in angiogenesis. Kaposi's Sarcoma-associated herpesvirus (KSHV) is the etiologic agent of KS and is likely involved in both tumor formation and the induction of angiogenesis. Integrins, and specifically integrin αVβ3, have known roles in both tumor induction and angiogenesis. αVβ3 is also important for KSHV infection as it has been shown to be involved in KSHV entry into cells. We found that during latent infection of endothelial cells KSHV induces the expression of integrin β3 leading to increased surface levels of αVβ3. Signaling molecules downstream of integrins, including FAK and Src, are activated during viral latency. Integrin activation by KSHV is necessary for the KSHV-associated upregulation of a number of angiogenic phenotypes during latent infection including adhesion and motility. Additionally, KSHV-infected cells become more reliant on αVβ3 for capillary like formation in three dimensional culture. KSHV induction of integrin β3, leading to induction of angiogenic and cancer cell phenotypes during latency, is likely to be important for KS tumor formation and potentially provides a novel target for treating KS tumors.
authors.affiliation: Department of Microbiology, University of Washington, Seattle, Washington, United States of America.
authors.forename: Terri A
authors.initials: TA
authors.lastname: DiMaio
authors.forename: Kimberley D
authors.initials: KD
authors.lastname: Gutierrez
authors.forename: Michael
authors.initials: M
authors.lastname: Lagunoff
mesh_terms: D002448:Cell Adhesion / Q000235:genetics; D002460:Cell Line; D002465:Cell Movement / Q000235:genetics; D002469:Cell Separation; D042783:Endothelial Cells / Q000378:metabolism / Q000821:virology*; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D019288:Herpesvirus 8, Human / Q000502:physiology*; D006801:Humans; D039661:Integrin beta3 / Q000096:biosynthesis*; D009389:Neovascularization, Pathologic / Q000235:genetics*; D010641:Phenotype; D034741:RNA, Small Interfering; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012514:Sarcoma, Kaposi / Q000235:genetics / Q000378:metabolism / Q000821:virology*; D015398:Signal Transduction / Q000502:physiology; D017735:Virus Latency / Q000502:physiology*
chemical_list: D039661:Integrin beta3; D034741:RNA, Small Interfering