Liver X Receptors Suppress Activity of Cholesterol and Fatty Acid Synthesis Pathways To Oppose Gammaherpesvirus Replication

ABSTRACT Gammaherpesviruses are oncogenic pathogens that persist in ~95% of the adult population. Cellular metabolic pathways have emerged as important regulators of many viral infections, including infections by gammaherpesviruses that require several lipid synthetic pathways for optimal replicatio...

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Autores principales:	P. T. Lange, C. Schorl, D. Sahoo, V. L. Tarakanova
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2018
Materias:	cholesterol synthesis fatty acid synthesis gammaherpesvirus liver X receptors macrophages Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/57a85855163446babd30e11b5cb62c18
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spelling	oai:doaj.org-article:57a85855163446babd30e11b5cb62c182021-11-15T16:00:14ZLiver X Receptors Suppress Activity of Cholesterol and Fatty Acid Synthesis Pathways To Oppose Gammaherpesvirus Replication10.1128/mBio.01115-182150-7511https://doaj.org/article/57a85855163446babd30e11b5cb62c182018-09-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01115-18https://doaj.org/toc/2150-7511ABSTRACT Gammaherpesviruses are oncogenic pathogens that persist in ~95% of the adult population. Cellular metabolic pathways have emerged as important regulators of many viral infections, including infections by gammaherpesviruses that require several lipid synthetic pathways for optimal replication. Liver X receptors (LXRs) are transcription factors that are critical regulators of cellular fatty acid and cholesterol synthesis pathways. Not surprisingly, LXRs are attractive therapeutic targets in cardiovascular disease. Here we describe an antiviral role for LXRs in the context of gammaherpesvirus infection of primary macrophages. We show that type I interferon increased LXR expression following infection. Surprisingly, there was not a corresponding induction of LXR target genes. Rather, LXRs suppressed the expression of target genes, leading to decreased fatty acid and cholesterol synthesis, two metabolic pathways that support gammaherpesvirus replication. This report defines LXR-mediated restriction of cholesterol and lipid synthesis as an intrinsic metabolic mechanism to restrict viral replication in innate immune cells. IMPORTANCE Fatty acid and cholesterol synthesis pathways of the host play important roles in diverse biological systems. Importantly, these two metabolic pathways are also usurped by a number of viruses to facilitate viral replication. In this report, we show that suppression of these pathways by liver X receptors in primary macrophages creates an intrinsic antiviral state that attenuates gammaherpesvirus replication by limiting viral access to the two metabolic pathways.P. T. LangeC. SchorlD. SahooV. L. TarakanovaAmerican Society for Microbiologyarticlecholesterol synthesisfatty acid synthesisgammaherpesvirusliver X receptorsmacrophagesMicrobiologyQR1-502ENmBio, Vol 9, Iss 4 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	cholesterol synthesis fatty acid synthesis gammaherpesvirus liver X receptors macrophages Microbiology QR1-502
spellingShingle	cholesterol synthesis fatty acid synthesis gammaherpesvirus liver X receptors macrophages Microbiology QR1-502 P. T. Lange C. Schorl D. Sahoo V. L. Tarakanova Liver X Receptors Suppress Activity of Cholesterol and Fatty Acid Synthesis Pathways To Oppose Gammaherpesvirus Replication
description	ABSTRACT Gammaherpesviruses are oncogenic pathogens that persist in ~95% of the adult population. Cellular metabolic pathways have emerged as important regulators of many viral infections, including infections by gammaherpesviruses that require several lipid synthetic pathways for optimal replication. Liver X receptors (LXRs) are transcription factors that are critical regulators of cellular fatty acid and cholesterol synthesis pathways. Not surprisingly, LXRs are attractive therapeutic targets in cardiovascular disease. Here we describe an antiviral role for LXRs in the context of gammaherpesvirus infection of primary macrophages. We show that type I interferon increased LXR expression following infection. Surprisingly, there was not a corresponding induction of LXR target genes. Rather, LXRs suppressed the expression of target genes, leading to decreased fatty acid and cholesterol synthesis, two metabolic pathways that support gammaherpesvirus replication. This report defines LXR-mediated restriction of cholesterol and lipid synthesis as an intrinsic metabolic mechanism to restrict viral replication in innate immune cells. IMPORTANCE Fatty acid and cholesterol synthesis pathways of the host play important roles in diverse biological systems. Importantly, these two metabolic pathways are also usurped by a number of viruses to facilitate viral replication. In this report, we show that suppression of these pathways by liver X receptors in primary macrophages creates an intrinsic antiviral state that attenuates gammaherpesvirus replication by limiting viral access to the two metabolic pathways.
format	article
author	P. T. Lange C. Schorl D. Sahoo V. L. Tarakanova
author_facet	P. T. Lange C. Schorl D. Sahoo V. L. Tarakanova
author_sort	P. T. Lange
title	Liver X Receptors Suppress Activity of Cholesterol and Fatty Acid Synthesis Pathways To Oppose Gammaherpesvirus Replication
title_short	Liver X Receptors Suppress Activity of Cholesterol and Fatty Acid Synthesis Pathways To Oppose Gammaherpesvirus Replication
title_full	Liver X Receptors Suppress Activity of Cholesterol and Fatty Acid Synthesis Pathways To Oppose Gammaherpesvirus Replication
title_fullStr	Liver X Receptors Suppress Activity of Cholesterol and Fatty Acid Synthesis Pathways To Oppose Gammaherpesvirus Replication
title_full_unstemmed	Liver X Receptors Suppress Activity of Cholesterol and Fatty Acid Synthesis Pathways To Oppose Gammaherpesvirus Replication
title_sort	liver x receptors suppress activity of cholesterol and fatty acid synthesis pathways to oppose gammaherpesvirus replication
publisher	American Society for Microbiology
publishDate	2018
url	https://doaj.org/article/57a85855163446babd30e11b5cb62c18
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Liver X Receptors Suppress Activity of Cholesterol and Fatty Acid Synthesis Pathways To Oppose Gammaherpesvirus Replication

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