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Viruses 2019, 11(2), 97; https://doi.org/10.3390/v11020097

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
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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.
Received: 16 October 2018 / Revised: 16 January 2019 / Accepted: 18 January 2019 / Published: 24 January 2019
(This article belongs to the Special Issue Noroviruses)
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Abstract

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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