title: KSHV-Mediated Angiogenesis in Tumor Progression.
abstract: Human herpesvirus 8 (HHV-8), also known as Kaposi's sarcoma-associated herpesvirus (KSHV), is a malignant human oncovirus belonging to the gamma herpesvirus family. HHV-8 is closely linked to the pathogenesis of Kaposi's sarcoma (KS) and two other B-cell lymphoproliferative diseases: primary effusion lymphoma (PEL) and a plasmablastic variant of multicentric Castleman's disease (MCD). KS is an invasive tumor of endothelial cells most commonly found in untreated HIV-AIDS or immuno-compromised individuals. KS tumors are highly vascularized and have abnormal, excessive neo-angiogenesis, inflammation, and proliferation of infected endothelial cells. KSHV directly induces angiogenesis in an autocrine and paracrine fashion through a complex interplay of various viral and cellular pro-angiogenic and inflammatory factors. KS is believed to originate due to a combination of KSHV's efficient strategies for evading host immune systems and several pro-angiogenic and pro-inflammatory stimuli. In addition, KSHV infection of endothelial cells produces a wide array of viral oncoproteins with transforming capabilities that regulate multiple host-signaling pathways involved in the activation of angiogenesis. It is likely that the cellular-signaling pathways of angiogenesis and lymph-angiogenesis modulate the rate of tumorigenesis induction by KSHV. This review summarizes the current knowledge on regulating KSHV-mediated angiogenesis by integrating the findings reported thus far on the roles of host and viral genes in oncogenesis, recent developments in cell-culture/animal-model systems, and various anti-angiogenic therapies for treating KSHV-related lymphoproliferative disorders.
authors.affiliation: Department of Microbiology and Immunology, University of Nevada, Reno, School of Medicine, 1664 N Virginia Street, MS 320, Reno, NV 89557, USA. pravinp@medicine.nevada.edu.
authors.forename: Pravinkumar
authors.initials: P
authors.lastname: Purushothaman
authors.affiliation: Department of Microbiology and Immunology, University of Nevada, Reno, School of Medicine, 1664 N Virginia Street, MS 320, Reno, NV 89557, USA. tuppal@medicine.nevada.edu.
authors.forename: Timsy
authors.initials: T
authors.lastname: Uppal
authors.affiliation: Department of Microbiology and Immunology, University of Nevada, Reno, School of Medicine, 1664 N Virginia Street, MS 320, Reno, NV 89557, USA. rsarkar@medicine.nevada.edu.
authors.forename: Roni
authors.initials: R
authors.lastname: Sarkar
authors.affiliation: Department of Microbiology and Immunology, University of Nevada, Reno, School of Medicine, 1664 N Virginia Street, MS 320, Reno, NV 89557, USA. scverma@medicine.nevada.edu.
authors.forename: Subhash C
authors.initials: SC
authors.lastname: Verma
mesh_terms: D000818:Animals; D018450:Disease Progression; D019288:Herpesvirus 8, Human / Q000472:pathogenicity*; D054884:Host-Pathogen Interactions; D006801:Humans; D009389:Neovascularization, Pathologic; D012514:Sarcoma, Kaposi / Q000473:pathology* / Q000821:virology*
keywords: KSHV; Kaposi’s sarcoma; Kaposi’s sarcoma-associated herpesvirus; angiogenesis; lymphangiogenesis; oncogenesis; oncoproteins