CCL2 and CCL5 driven attraction of CD172a+ monocytic cells during an equine herpesvirus type 1 (EHV-1) infection in equine nasal mucosa and the impact of two migration inhibitors, rosiglitazone (RSG) and quinacrine (QC)

Jing Zhao,Jolien Van Cleemput,Katrien C K Poelaert,Hans J Nauwynck

doi:10.1186/s13567-017-0419-4

Jing Zhao, Jolien Van Cleemput + Show 2 more

Open Access

https://doi.org/10.1186/s13567-017-0419-4

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Journal: Veterinary Research	Publication Date: Feb 27, 2017
Citations: 13	License type: open-access

Affiliation: Ghent University

Abstract

Equine herpesvirus type 1 (EHV-1) causes respiratory disease, abortion and neurological disorders in horses. Besides epithelial cells, CD172a+ monocytic cells become infected with EHV-1 in the respiratory mucosa and transport the virus from the apical side of the epithelium to the lamina propria en route to the lymph and blood circulation. Whether CD172a+ monocytic cells are specifically recruited to the infection sites in order to pick up virus is unknown. In our study, equine nasal mucosa explants were inoculated with EHV-1 neurological strains 03P37 and 95P105 or the non-neurological strains 97P70 and 94P247 and the migration of monocytic cells was examined by immunofluorescence. Further, the role of monokines CCL2 and CCL5 was determined and the effect of migration inhibitors rosiglitazone (RSG) or quinacrine was analyzed. It was shown that with neurological strains but not with the non-neurological strains, CD172a+ cells specifically migrated towards EHV-1 infected regions and that CCL2 and CCL5 were involved. CCL2 started to be expressed in infected epithelial cells at 24 h post-incubation (hpi) and CCL5 at 48 hpi, which corresponded with the CD172a+ migration. RSG treatment of EHV-1-inoculated equine nasal mucosa had no effect on the virus replication in the epithelium, but decreased the migration of CD172a+ cells in the lamina propria. Overall, these findings bring new insights in the early pathogenesis of EHV-1 infections, illustrate differences between neurological and non-neurological strains and show the way for EHV-1 treatment.

Highlights

Equine herpesvirus 1 (EHV-1) is an important pathogen of horses
The localization and quantification of CD172a+ cells in the equine nasal mucosa explants infected with EHV‐1 In mock-inoculated nasal mucosa, the CD172a+ cells were mainly localized in the lamina propria underneath the basement membrane (BM)
At 72 hpi, nearly no EHV-1 infected CD172a+ cells were found in the epithelium while there were much more EHV-1 infected CD172a+ cells observed underneath the BM

Summary

Introduction

Equine herpesvirus 1 (EHV-1) is an important pathogen of horses. It is a member of the subfamily Alphaherpesvirinae with a 150 kb double stranded DNA genome [1]. Afterwards, a cell-associated viremia allows EHV-1 to reach internal organs such as the pregnant uterus and/or central nervous system (CNS). Replication in these organs may result in abortion, neonatal foal death and myeloencephalopathy [8, 9]. It has been reported that the neurological strains infect a higher number of CD172a+ cells than the abortigenic strains in the upper respiratory mucosa [5]

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