Kaposi's sarcoma herpesvirus microRNAs induce metabolic transformation of infected cells.

Altered cell metabolism is inherently connected with pathological conditions including cancer and viral infections. Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiological agent of Kaposi's sarcoma (KS). KS tumour cells display features of lymphatic endothelial differentiation an...

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Autores principales:	Ohad Yogev, Dimitris Lagos, Tariq Enver, Chris Boshoff
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/31d4ddc1da7c4f0c917825280bf144af
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spelling	oai:doaj.org-article:31d4ddc1da7c4f0c917825280bf144af2021-11-25T05:45:59ZKaposi's sarcoma herpesvirus microRNAs induce metabolic transformation of infected cells.1553-73661553-737410.1371/journal.ppat.1004400https://doaj.org/article/31d4ddc1da7c4f0c917825280bf144af2014-09-01T00:00:00Zhttps://doi.org/10.1371/journal.ppat.1004400https://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Altered cell metabolism is inherently connected with pathological conditions including cancer and viral infections. Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiological agent of Kaposi's sarcoma (KS). KS tumour cells display features of lymphatic endothelial differentiation and in their vast majority are latently infected with KSHV, while a small number are lytically infected, producing virions. Latently infected cells express only a subset of viral genes, mainly located within the latency-associated region, among them 12 microRNAs. Notably, the metabolic properties of KSHV-infected cells closely resemble the metabolic hallmarks of cancer cells. However, how and why KSHV alters host cell metabolism remains poorly understood. Here, we investigated the effect of KSHV infection on the metabolic profile of primary dermal microvascular lymphatic endothelial cells (LEC) and the functional relevance of this effect. We found that the KSHV microRNAs within the oncogenic cluster collaborate to decrease mitochondria biogenesis and to induce aerobic glycolysis in infected cells. KSHV microRNAs expression decreases oxygen consumption, increase lactate secretion and glucose uptake, stabilize HIF1α and decreases mitochondria copy number. Importantly this metabolic shift is important for latency maintenance and provides a growth advantage. Mechanistically we show that KSHV alters host cell energy metabolism through microRNA-mediated down regulation of EGLN2 and HSPA9. Our data suggest that the KSHV microRNAs induce a metabolic transformation by concurrent regulation of two independent pathways; transcriptional reprograming via HIF1 activation and reduction of mitochondria biogenesis through down regulation of the mitochondrial import machinery. These findings implicate viral microRNAs in the regulation of the cellular metabolism and highlight new potential avenues to inhibit viral latency.Ohad YogevDimitris LagosTariq EnverChris BoshoffPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 10, Iss 9, p e1004400 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Ohad Yogev Dimitris Lagos Tariq Enver Chris Boshoff Kaposi's sarcoma herpesvirus microRNAs induce metabolic transformation of infected cells.
description	Altered cell metabolism is inherently connected with pathological conditions including cancer and viral infections. Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiological agent of Kaposi's sarcoma (KS). KS tumour cells display features of lymphatic endothelial differentiation and in their vast majority are latently infected with KSHV, while a small number are lytically infected, producing virions. Latently infected cells express only a subset of viral genes, mainly located within the latency-associated region, among them 12 microRNAs. Notably, the metabolic properties of KSHV-infected cells closely resemble the metabolic hallmarks of cancer cells. However, how and why KSHV alters host cell metabolism remains poorly understood. Here, we investigated the effect of KSHV infection on the metabolic profile of primary dermal microvascular lymphatic endothelial cells (LEC) and the functional relevance of this effect. We found that the KSHV microRNAs within the oncogenic cluster collaborate to decrease mitochondria biogenesis and to induce aerobic glycolysis in infected cells. KSHV microRNAs expression decreases oxygen consumption, increase lactate secretion and glucose uptake, stabilize HIF1α and decreases mitochondria copy number. Importantly this metabolic shift is important for latency maintenance and provides a growth advantage. Mechanistically we show that KSHV alters host cell energy metabolism through microRNA-mediated down regulation of EGLN2 and HSPA9. Our data suggest that the KSHV microRNAs induce a metabolic transformation by concurrent regulation of two independent pathways; transcriptional reprograming via HIF1 activation and reduction of mitochondria biogenesis through down regulation of the mitochondrial import machinery. These findings implicate viral microRNAs in the regulation of the cellular metabolism and highlight new potential avenues to inhibit viral latency.
format	article
author	Ohad Yogev Dimitris Lagos Tariq Enver Chris Boshoff
author_facet	Ohad Yogev Dimitris Lagos Tariq Enver Chris Boshoff
author_sort	Ohad Yogev
title	Kaposi's sarcoma herpesvirus microRNAs induce metabolic transformation of infected cells.
title_short	Kaposi's sarcoma herpesvirus microRNAs induce metabolic transformation of infected cells.
title_full	Kaposi's sarcoma herpesvirus microRNAs induce metabolic transformation of infected cells.
title_fullStr	Kaposi's sarcoma herpesvirus microRNAs induce metabolic transformation of infected cells.
title_full_unstemmed	Kaposi's sarcoma herpesvirus microRNAs induce metabolic transformation of infected cells.
title_sort	kaposi's sarcoma herpesvirus micrornas induce metabolic transformation of infected cells.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/31d4ddc1da7c4f0c917825280bf144af
work_keys_str_mv	AT ohadyogev kaposissarcomaherpesvirusmicrornasinducemetabolictransformationofinfectedcells AT dimitrislagos kaposissarcomaherpesvirusmicrornasinducemetabolictransformationofinfectedcells AT tariqenver kaposissarcomaherpesvirusmicrornasinducemetabolictransformationofinfectedcells AT chrisboshoff kaposissarcomaherpesvirusmicrornasinducemetabolictransformationofinfectedcells
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Kaposi's sarcoma herpesvirus microRNAs induce metabolic transformation of infected cells.

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