The Oxysterol 25-Hydroxycholesterol Inhibits Replication of Murine Norovirus.



Shawli, Ghada T, Adeyemi, Oluwapelumi O ORCID: 0000-0002-0848-5917, Stonehouse, Nicola J ORCID: 0000-0003-1146-5519 and Herod, Morgan R ORCID: 0000-0002-8626-6787
(2019) The Oxysterol 25-Hydroxycholesterol Inhibits Replication of Murine Norovirus. Viruses, 11 (2).

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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.

Item Type: Article
Uncontrolled Keywords: Macrophages, Animals, Mice, Norovirus, Hydroxycholesterols, Antiviral Agents, Virus Replication, Apoptosis, Caspase 3, RAW 264.7 Cells
Depositing User: Symplectic Admin
Date Deposited: 05 Jun 2019 09:11
Last Modified: 19 Nov 2019 17:10
DOI: 10.3390/v11020097
Open Access URL: https://doi.org/10.3390/v11020097
URI: http://livrepository.liverpool.ac.uk/id/eprint/3044538
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