U18666A, an intra-cellular cholesterol transport inhibitor, inhibits dengue virus entry and replication

Mee Kian Poh; Guanghou Shui; Xuping Xie; Pei Yong Shi; Markus R. Wenk; Feng Gu

doi:10.1016/j.antiviral.2011.11.014

U18666A, an intra-cellular cholesterol transport inhibitor, inhibits dengue virus entry and replication

Mee Kian Poh, Guanghou Shui, Xuping Xie, Pei Yong Shi, Markus R. Wenk, Feng Gu

Research output: Contribution to journal › Article › peer-review

73 Scopus citations

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.

Original language	English (US)
Pages (from-to)	191-198
Number of pages	8
Journal	Antiviral research
Volume	93
Issue number	1
DOIs	https://doi.org/10.1016/j.antiviral.2011.11.014
State	Published - Jan 2012
Externally published	Yes

Keywords

Antiviral
Cholesterol
Dengue virus
Fatty acids
U18666A

ASJC Scopus subject areas

Pharmacology
Virology

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10.1016/j.antiviral.2011.11.014

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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.",

keywords = "Antiviral, Cholesterol, Dengue virus, Fatty acids, U18666A",

author = "Poh, {Mee Kian} and Guanghou Shui and Xuping Xie and Shi, {Pei Yong} and Wenk, {Markus R.} and Feng Gu",

note = "Funding Information: We would like to acknowledge Wouter Schul, Mary Ng and Yuru Deng for their scientific discussion. Work in the laboratory of M.R.W. is supported in part by grants from the Singapore National Research Foundation under CRP Award No. 2007-04. ",

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AU - Shi, Pei Yong

AU - Wenk, Markus R.

AU - Gu, Feng

N1 - Funding Information: We would like to acknowledge Wouter Schul, Mary Ng and Yuru Deng for their scientific discussion. Work in the laboratory of M.R.W. is supported in part by grants from the Singapore National Research Foundation under CRP Award No. 2007-04.

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N2 - 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.

AB - 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.

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KW - Fatty acids

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U18666A, an intra-cellular cholesterol transport inhibitor, inhibits dengue virus entry and replication

Abstract

Keywords

ASJC Scopus subject areas

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