title: U18666A, an intra-cellular cholesterol transport inhibitor, inhibits dengue virus entry and replication.
abstract: The level of cholesterol in host cells has been shown to affect viral infection. However, it is still not understood why this level of regulation is important for successful infection. We have shown in this study that dengue virus infection was affected when the cholesterol intake in infected cells was disrupted using a cholesterol transport inhibitor, U18666A. The antiviral effect was found to result from two events: retarded viral trafficking in the cholesterol-loaded late endosomes/lysosomes and suppressed de novo sterol biosynthesis in treated infected cells. We also observed an additive antiviral effect of U18666A with C75, a fatty acid synthase inhibitor, suggesting dengue virus relies on both the host cholesterol and fatty acid biosynthesis for successful replication.
authors.affiliation: Dengue Unit, Novartis Institute for Tropical Diseases, 10 Biopolis Road, Chromos #05-01, Singapore 138670, Singapore.
authors.forename: Mee Kian
authors.initials: MK
authors.lastname: Poh
authors.forename: Guanghou
authors.initials: G
authors.lastname: Shui
authors.forename: Xuping
authors.initials: X
authors.lastname: Xie
authors.forename: Pei-Yong
authors.initials: PY
authors.lastname: Shi
authors.forename: Markus R
authors.initials: MR
authors.lastname: Wenk
authors.forename: Feng
authors.initials: F
authors.lastname: Gu
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives / Q000494:pharmacology; D000736:Androstenes / Q000494:pharmacology*; D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D000998:Antiviral Agents / Q000494:pharmacology*; D001692:Biological Transport / Q000187:drug effects; D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism*; D006224:Cricetinae; D003716:Dengue Virus / Q000187:drug effects*; D004357:Drug Synergism; D011992:Endosomes / Q000187:drug effects / Q000378:metabolism; D064429:Fatty Acid Synthases / Q000037:antagonists & inhibitors; D006801:Humans; D008247:Lysosomes / Q000187:drug effects / Q000378:metabolism; D053586:Virus Internalization / Q000187:drug effects*; D014779:Virus Replication / Q000187:drug effects*
chemical_list: C406734:4-methylene-2-octyl-5-oxofuran-3-carboxylic acid; D000736:Androstenes; D000924:Anticholesteremic Agents; D000998:Antiviral Agents; C006261:3-beta-(2-(diethylamino)ethoxy)androst-5-en-17-one; D002784:Cholesterol; D064429:Fatty Acid Synthases; D015107:4-Butyrolactone