Entry of equid herpesvirus 1 into CD172a+ monocytic cells.
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 αVβ3 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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EHV-1 binds to a limited number of CD172a+ cells compared to RK-13 cells, suggesting that a block at the virus binding level might be partially responsible for restricted viral replication in these cells.
“EHV-1 bound to a limited number of CD172a+ cells compared to RK-13 cells, suggesting that a block at the virus binding level might be partially responsible for the restricted viral replication in these cells.”
From The Pathogenesis and Immune Evasive Mechanisms of Equine Herpesvirus Type 1 (2021) · cites this paper as Laval et al., 2016
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“Laval and colleagues further investigated the molecular mechanisms underlying the restricted infection of EHV-1 in CD172a+ cells (Laval et al., 2016).”
BackgroundVan Cleemput, J., Poelaert, K. C. K., Laval, K., Maes, R., Hussey, G. S., Van den Broeck, W., & Nauwynck, H. J. (2017) · Scientific Reports · doi:10.1038/s41598-017-16804-5 · Cited by 34 · see citing works
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Khan, M. Z., Ji, Y., Fan, X., Liu, Y., Liu, W., & Wang, C. (2025) · Veterinary Sciences · doi:10.3390/vetsci12111082 · Cited by 5 · see citing works
- Authors
- Laval, K., Favoreel, H. W., Van Cleemput, J., Poelaert, K. C. K., Brown, I. K., Verhasselt, B., & Nauwynck, H. J.
- Affiliations
- Ghent University (BE)
- Department of Virology, Parasitology and Immunology, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820 Merelbeke, Belgium
- Venue
- Journal of General Virology
- Publisher
- Microbiology Society
- Published
- 2016-03-01
- Volume
- 97
- Issue
- 3
- Pages
- 733-746
- ISSN
- 0022-1317 (ISSN-L)
- 1465-2099
- OpenAlex
- W2209888188
- Cited by
- 12
- References
- 57
- Citations by year
- 2025: 3 · 2023: 1 · 2021: 1 · 2020: 1 · 2017: 1 · 2016: 5
- FWCI
- 1.57
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of General Virology (publishedVersion)
- PubMed (publishedVersion)
- Ghent University Academic Bibliography (Ghent University) (submittedVersion)
- Funders
- Louisiana State University
- Belgian Federal Science Policy Office
- Fonds Wetenschappelijk Onderzoek (11Y5415N)
- Universiteit Gent
- Vlaamse regering
- Topics
- Health Sciences › Medicine › Epidemiology › Herpesvirus Infections and Treatments
- Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Virus Infections Studies
- Health Sciences › Medicine › Epidemiology › Virology and Viral Diseases
- Keywords
- equine herpesvirus 1, viral entry, sialic acid, neuraminidase, integrin αvβ3, phagocytosis, heparan sulfate, viral tropism, cell receptors, endosomal acidification, horses
- MeSH terms
- Animals, Antigens, Differentiation, Herpesvirus 1, Equid, Herpesviridae Infections, Horse Diseases, Horses, Monocytes, Virus Internalization, Host-Pathogen Interactions
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