Faculty Collaboration Database

Liver X Receptors Suppress Activity of Cholesterol and Fatty Acid Synthesis Pathways To Oppose Gammaherpesvirus Replication. mBio 2018 Jul 17;9(4)

Date

07/19/2018

Pubmed ID

30018108

Pubmed Central ID

PMC6050960

DOI

10.1128/mBio.01115-18

Scopus ID

2-s2.0-85055540133 (requires institutional sign-in at Scopus site)   19 Citations

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.

Author List

Lange PT, Schorl C, Sahoo D, Tarakanova VL

Authors

Daisy Sahoo PhD Dean, Professor in the Medicine department at Medical College of Wisconsin
Vera Tarakanova PhD Professor in the Microbiology and Immunology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Antiviral Agents
Biosynthetic Pathways
Cells, Cultured
Cholesterol
DNA, Viral
Fatty Acids
Gammaherpesvirinae
Gene Expression
Host-Pathogen Interactions
Interferon Type I
Liver X Receptors
Macrophages
Mice, Inbred C57BL
RNA, Messenger
Virus Replication