KSHV-Mediated Angiogenesis in Tumor Progression

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Authors

Purushothaman, Pravinkumar
Uppal, Timsy
Sarkar, Roni
Verma, Subhash C.

Issue Date

2016

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Article

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Keywords

Kaposi's sarcoma-associated herpesvirus , KSHV , Kaposi's sarcoma , angiogenesis , lymphangiogenesis , oncogenesis , oncoproteins

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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.

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Citation

Purushothaman, P., Uppal, T., Sarkar, R., & Verma, S. (2016). KSHV-Mediated Angiogenesis in Tumor Progression. Viruses, 8(7), 198. doi:10.3390/v8070198

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Creative Commons Attribution 4.0 International

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1999-4915

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