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KSHV requires vCyclin to overcome replicative senescence in primary human lymphatic endothelial cells

Kaposi’s Sarcoma Herpesvirus (KSHV) is present in the main tumor cells of Kaposi’s Sarcoma (KS), the spindle cells, which are of endothelial origin. KSHV is also associated with two B-cell lymphomas, Primary Effusion Lymphoma (PEL) and Multicentric Castleman’s Disease. In KS and PEL, KSHV is primari...

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Autores principales: DiMaio, Terri A., Vogt, Daniel T., Lagunoff, Michael
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7326280/
https://www.ncbi.nlm.nih.gov/pubmed/32555637
http://dx.doi.org/10.1371/journal.ppat.1008634
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author DiMaio, Terri A.
Vogt, Daniel T.
Lagunoff, Michael
author_facet DiMaio, Terri A.
Vogt, Daniel T.
Lagunoff, Michael
author_sort DiMaio, Terri A.
collection PubMed
description Kaposi’s Sarcoma Herpesvirus (KSHV) is present in the main tumor cells of Kaposi’s Sarcoma (KS), the spindle cells, which are of endothelial origin. KSHV is also associated with two B-cell lymphomas, Primary Effusion Lymphoma (PEL) and Multicentric Castleman’s Disease. In KS and PEL, KSHV is primarily latent in the infected cells, expressing only a few genes. Although KSHV infection is required for KS and PEL, it is unclear how latent gene expression contributes to their formation. Proliferation of cancer cells occurs despite multiple checkpoints intended to prevent dysregulated cell growth. The first of these checkpoints, caused by shortening of telomeres, results in replicative senescence, where cells are metabolically active, but no longer divide. We found that human dermal lymphatic endothelial cells (LECs) are more susceptible to KSHV infection than their blood-specific endothelial cell counterparts and maintain KSHV latency to higher levels during passage. Importantly, KSHV infection of human LECs but not human BECs promotes their continued proliferation beyond this first checkpoint of replicative senescence. The latently expressed viral cyclin homolog is essential for KSHV-induced bypass of senescence in LECs. These data suggest that LECs may be an important reservoir for KSHV infection and may play a role during KS tumor development and that the viral cyclin is a critical oncogene for this process.
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spelling pubmed-73262802020-07-10 KSHV requires vCyclin to overcome replicative senescence in primary human lymphatic endothelial cells DiMaio, Terri A. Vogt, Daniel T. Lagunoff, Michael PLoS Pathog Research Article Kaposi’s Sarcoma Herpesvirus (KSHV) is present in the main tumor cells of Kaposi’s Sarcoma (KS), the spindle cells, which are of endothelial origin. KSHV is also associated with two B-cell lymphomas, Primary Effusion Lymphoma (PEL) and Multicentric Castleman’s Disease. In KS and PEL, KSHV is primarily latent in the infected cells, expressing only a few genes. Although KSHV infection is required for KS and PEL, it is unclear how latent gene expression contributes to their formation. Proliferation of cancer cells occurs despite multiple checkpoints intended to prevent dysregulated cell growth. The first of these checkpoints, caused by shortening of telomeres, results in replicative senescence, where cells are metabolically active, but no longer divide. We found that human dermal lymphatic endothelial cells (LECs) are more susceptible to KSHV infection than their blood-specific endothelial cell counterparts and maintain KSHV latency to higher levels during passage. Importantly, KSHV infection of human LECs but not human BECs promotes their continued proliferation beyond this first checkpoint of replicative senescence. The latently expressed viral cyclin homolog is essential for KSHV-induced bypass of senescence in LECs. These data suggest that LECs may be an important reservoir for KSHV infection and may play a role during KS tumor development and that the viral cyclin is a critical oncogene for this process. Public Library of Science 2020-06-18 /pmc/articles/PMC7326280/ /pubmed/32555637 http://dx.doi.org/10.1371/journal.ppat.1008634 Text en © 2020 DiMaio et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
DiMaio, Terri A.
Vogt, Daniel T.
Lagunoff, Michael
KSHV requires vCyclin to overcome replicative senescence in primary human lymphatic endothelial cells
title KSHV requires vCyclin to overcome replicative senescence in primary human lymphatic endothelial cells
title_full KSHV requires vCyclin to overcome replicative senescence in primary human lymphatic endothelial cells
title_fullStr KSHV requires vCyclin to overcome replicative senescence in primary human lymphatic endothelial cells
title_full_unstemmed KSHV requires vCyclin to overcome replicative senescence in primary human lymphatic endothelial cells
title_short KSHV requires vCyclin to overcome replicative senescence in primary human lymphatic endothelial cells
title_sort kshv requires vcyclin to overcome replicative senescence in primary human lymphatic endothelial cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7326280/
https://www.ncbi.nlm.nih.gov/pubmed/32555637
http://dx.doi.org/10.1371/journal.ppat.1008634
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