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Open AccessArticle

The Oxysterol 25-Hydroxycholesterol Inhibits Replication of Murine Norovirus

School of Molecular and Cellular Biology, Faculty of Biological Sciences and Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds LS2 9JT, UK
Author to whom correspondence should be addressed.
Current Address: Department of Infection Biology, Institute of Infection and Global Health, University of Liverpool, Liverpool L69 7ZX, United Kingdom.
Current Address: Department of Medical Microbiology and Parasitology, Faculty of Basic Medical Sciences, College of Health Sciences, University of Ilorin, Ilorin, Nigeria.
Viruses 2019, 11(2), 97;
Received: 16 October 2018 / Revised: 16 January 2019 / Accepted: 18 January 2019 / Published: 24 January 2019
(This article belongs to the Special Issue Noroviruses)
Cholesterol, an essential component of mammalian cells, is also an important factor in the replicative-cycles of several human and animal viruses. The oxysterol, 25-hydroxycholesterol, is produced from cholesterol by the enzyme, cholesterol 25-hydroxylase. 25-hydroxycholesterol (25-HC) has been shown to have anti-viral activities against a wide range of viruses, including a range of positive-sense RNA viruses. In this study, we have investigated the role of 25-HC in norovirus replication using murine norovirus (MNV) as a model system. As a control, we employed herpes simplex virus-1 (HSV-1), a pathogen previously shown to be inhibited by 25-HC. Consistent with previous studies, 25-HC inhibited HSV-1 replication in the MNV-susceptible cell line, RAW264.7. Treating RAW264.7 cells with sub-cytotoxic concentrations of 25-HC reduced the MNV titers. However, other sterols such as cholesterol or the oxysterol, 22-S-hydroxycholesterol (22-S-HC), did not inhibit MNV replication. Moreover, treating MNV-infected RAW264.7 cells with 25-HC-stimulated caspase 3/7 activity, which leads to enhanced apoptosis and increased cell death. Our study adds noroviruses to the list of viruses inhibited by 25-HC and begins to offer insights into the mechanism behind this inhibition. View Full-Text
Keywords: 25-HC; Murine norovirus; Nystatin; MNV; Replication; Apoptosis 25-HC; Murine norovirus; Nystatin; MNV; Replication; Apoptosis
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Shawli, G.T.; Adeyemi, O.O.; Stonehouse, N.J.; Herod, M.R. The Oxysterol 25-Hydroxycholesterol Inhibits Replication of Murine Norovirus. Viruses 2019, 11, 97.

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