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• W2489071034 abstract "ABSTRACT Cell culture systems reproducing virus replication can serve as unique models for the discovery of novel bioactive molecules. Here, using a hepatitis C virus (HCV) cell culture system, we identified neoechinulin B (NeoB), a fungus-derived compound, as an inhibitor of the liver X receptor (LXR). NeoB was initially identified by chemical screening as a compound that impeded the production of infectious HCV. Genome-wide transcriptome analysis and reporter assays revealed that NeoB specifically inhibits LXR-mediated transcription. NeoB was also shown to interact directly with LXRs. Analysis of structural analogs suggested that the molecular interaction of NeoB with LXR correlated with the capacity to inactivate LXR-mediated transcription and to modulate lipid metabolism in hepatocytes. Our data strongly suggested that NeoB is a novel LXR antagonist. Analysis using NeoB as a bioprobe revealed that LXRs support HCV replication: LXR inactivation resulted in dispersion of double-membrane vesicles, putative viral replication sites. Indeed, cells treated with NeoB showed decreased replicative permissiveness for poliovirus, which also replicates in double-membrane vesicles, but not for dengue virus, which replicates via a distinct membrane compartment. Together, our data suggest that LXR-mediated transcription regulates the formation of virus-associated membrane compartments. Significantly, inhibition of LXRs by NeoB enhanced the activity of all known classes of anti-HCV agents, and NeoB showed especially strong synergy when combined with interferon or an HCV NS5A inhibitor. Thus, our chemical genetics analysis demonstrates the utility of the HCV cell culture system for identifying novel bioactive molecules and characterizing the virus-host interaction machinery. IMPORTANCE Hepatitis C virus (HCV) is highly dependent on host factors for efficient replication. In the present study, we used an HCV cell culture system to screen an uncharacterized chemical library. Our results identified neoechinulin B (NeoB) as a novel inhibitor of the liver X receptor (LXR). NeoB inhibited the induction of LXR-regulated genes and altered lipid metabolism. Intriguingly, our results indicated that LXRs are critical to the process of HCV replication: LXR inactivation by NeoB disrupted double-membrane vesicles, putative sites of viral replication. Moreover, NeoB augmented the antiviral activity of all known classes of currently approved anti-HCV agents without increasing cytotoxicity. Thus, our strategy directly links the identification of novel bioactive compounds to basic virology and the development of new antiviral agents." @default.
• W2489071034 created "2016-08-23" @default.
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• W2489071034 date "2016-10-15" @default.
• W2489071034 modified "2023-10-16" @default.
• W2489071034 title "Fungus-Derived Neoechinulin B as a Novel Antagonist of Liver X Receptor, Identified by Chemical Genetics Using a Hepatitis C Virus Cell Culture System" @default.
• W2489071034 cites W178187152 @default.
• W2489071034 cites W1963509652 @default.
• W2489071034 cites W1964165453 @default.
• W2489071034 cites W1965694039 @default.
• W2489071034 cites W1969461545 @default.
• W2489071034 cites W1970828145 @default.
• W2489071034 cites W1992716708 @default.
• W2489071034 cites W1993496957 @default.
• W2489071034 cites W1999872639 @default.
• W2489071034 cites W2003173923 @default.
• W2489071034 cites W2003579943 @default.
• W2489071034 cites W2004009484 @default.
• W2489071034 cites W2005911243 @default.
• W2489071034 cites W2010672048 @default.
• W2489071034 cites W2013234678 @default.
• W2489071034 cites W2014290325 @default.
• W2489071034 cites W2021632088 @default.
• W2489071034 cites W2022103755 @default.
• W2489071034 cites W2022687771 @default.
• W2489071034 cites W2024136624 @default.
• W2489071034 cites W2024763248 @default.
• W2489071034 cites W2024851295 @default.
• W2489071034 cites W2025396954 @default.
• W2489071034 cites W2028215043 @default.
• W2489071034 cites W2031220581 @default.
• W2489071034 cites W2036955573 @default.
• W2489071034 cites W2040154453 @default.
• W2489071034 cites W2043892364 @default.
• W2489071034 cites W2044193462 @default.
• W2489071034 cites W2047411417 @default.
• W2489071034 cites W2048321326 @default.
• W2489071034 cites W2053172006 @default.
• W2489071034 cites W2054990533 @default.
• W2489071034 cites W2060061109 @default.
• W2489071034 cites W2061879307 @default.
• W2489071034 cites W2062378616 @default.
• W2489071034 cites W2064200824 @default.
• W2489071034 cites W2065040824 @default.
• W2489071034 cites W2065293328 @default.
• W2489071034 cites W2079724990 @default.
• W2489071034 cites W2083100985 @default.
• W2489071034 cites W2083277613 @default.
• W2489071034 cites W2085870527 @default.
• W2489071034 cites W2090439227 @default.
• W2489071034 cites W2102372344 @default.
• W2489071034 cites W2102373878 @default.
• W2489071034 cites W2102848212 @default.
• W2489071034 cites W2105962947 @default.
• W2489071034 cites W2106195907 @default.
• W2489071034 cites W2106608030 @default.
• W2489071034 cites W2110842901 @default.
• W2489071034 cites W2124211792 @default.
• W2489071034 cites W2127970706 @default.
• W2489071034 cites W2129810176 @default.
• W2489071034 cites W2130446847 @default.
• W2489071034 cites W2134760572 @default.
• W2489071034 cites W2134867985 @default.
• W2489071034 cites W2147126871 @default.
• W2489071034 cites W2148608191 @default.
• W2489071034 cites W2149500398 @default.
• W2489071034 cites W2151898297 @default.
• W2489071034 cites W2159425655 @default.
• W2489071034 cites W2160013852 @default.
• W2489071034 cites W2160697532 @default.
• W2489071034 cites W2171759277 @default.
• W2489071034 cites W2171962335 @default.
• W2489071034 cites W2467842752 @default.
• W2489071034 cites W28659707 @default.
• W2489071034 doi "https://doi.org/10.1128/jvi.00856-16" @default.
• W2489071034 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5044839" @default.
• W2489071034 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/27489280" @default.
• W2489071034 hasPublicationYear "2016" @default.

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