1887

Abstract

Equid herpesvirus 1 (EHV-1) causes respiratory disease, abortion and neurological disorders in horses. Cells from the myeloid lineage (CD172a) are one of the main target cells of EHV-1 during primary infection. Recently, we showed that EHV-1 restricts and delays its replication in CD172a cells as part of an immune-evasive strategy to disseminate to target organs. Here, we hypothesize that a low efficiency of EHV-1 binding to and entry in CD172a cells is responsible for this restriction. Thus, we characterized EHV-1 binding and entry into CD172a cells, and showed that EHV-1 only bound to 15–20 % of CD172a cells compared with 70 % of RK-13 control cells. Enzymic removal of heparan sulphate did not reduce EHV-1 infection, suggesting that EHV-1 does not use heparan sulphate to bind and enter CD172a cells. In contrast, we found that treatment of cells with neuraminidase (NA) reduced infection by 85–100 % compared with untreated cells, whilst NA treatment of virus had no effect on infection. This shows that sialic acid residues present on CD172a cells are essential in the initiation of EHV-1 infection. We found that αβ integrins are involved in the post-binding stage of CD172a cell infection. Using pharmacological inhibitors, we showed that EHV-1 does not enter CD172a cells via a clathrin- or caveolae-dependent endocytic pathway, nor by macropinocytosis, but requires cholesterol, tyrosine kinase, actin, dynamin and endosomal acidification, pointing towards a phagocytic mechanism. Overall, these results show that the narrow tropism of EHV-1 amongst CD172a cells is determined by the presence of specific cellular receptors.

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2016-03-01
2019-10-18
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