Thorne, L;
Lu, J;
Chaudhry, Y;
Bailey, D;
Goodfellow, I;
(2018)
Targeting macrophage- and intestinal epithelial cell-specific microRNAs against norovirus restricts replication in vivo.
Journal of General Virology
, 99
(12)
pp. 1621-1632.
10.1099/jgv.0.001065.
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Abstract
Until recently, our understanding of the cellular tropism of human norovirus (HuNoV), a major cause of viral gastroenteritis, has been limited. Immune cells and intestinal epithelial cells (IECs) have been proposed as targets of HuNoV replication in vivo, although the contribution of each to pathogenesis and transmission is unknown. Murine norovirus (MNV) is widely used as a surrogate model for HuNoV, as it replicates in cultured immune cells. The importance of the complete MNV immune cell tropism in vivo has not been determined. Recent work has linked replication in IECs to viral persistence in vivo. MNV provides a model to assess the relative contribution of each cell tropism to viral replication in immunocompetent native hosts. Here we exploited cell-specific microRNAs to control MNV replication, through insertion of microRNA target sequences into the MNV genome. We demonstrated the utility of this approach for MNV in vitro by selectively reducing replication in microglial cells, using microglial-specific miR-467c. We then showed that inserting a target sequence for the haematopoietic-specific miR-142-3p abrogated replication in a macrophage cell line. The presence of a target sequence for either miR-142-3p or IEC miR-215 significantly reduced viral secretion during the early stages of a persistent infection in immunocompetent mice, confirming that both cell types support viral replication in vivo. This study provides additional evidence that MNV shares the IEC tropism of HuNoVs in vivo, and now provides a model to dissect the contribution of replication in each cell type to viral pathogenesis and transmission in a native host.
| Type: | Article |
|---|---|
| Title: | Targeting macrophage- and intestinal epithelial cell-specific microRNAs against norovirus restricts replication in vivo |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1099/jgv.0.001065 |
| Publisher version: | https://doi.org/10.1099/jgv.0.001065 |
| Language: | English |
| Additional information: | This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. https://creativecommons.org/licenses/by/4.0/ |
| Keywords: | microRNA, haematopoetic cells, tropism, epithelial cells, Norovirus |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10076180 |
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