Abstract
The ancestral equine herpesvirus 1 (EHV1), closely related to human herpes viruses, exploits leukocytes to reach its target organs, accordingly evading the immune surveillance system. Circulating EHV1 strains can be divided into abortigenic/neurovirulent, causing reproductive/neurological disorders. Neurovirulent EHV1 more efficiently recruits monocytic CD172a+ cells to the upper respiratory tract (URT), while abortigenic EHV1 tempers monocyte migration. Whether similar results could be expected for T lymphocytes is not known. Therefore, we questioned whether differences in T cell recruitment could be associated with variations in cell tropism between both EHV1 phenotypes, and which viral proteins might be involved. The expression of CXCL9 and CXCL10 was evaluated in abortigenic/neurovirulent EHV1-inoculated primary respiratory epithelial cells (ERECs). The bioactivity of chemokines was tested with a functional migration assay. Replication of neurovirulent EHV1 in the URT resulted in an enhanced expression/bioactivity of CXCL9 and CXCL10, compared to abortigenic EHV1. Interestingly, deletion of glycoprotein 2 resulted in an increased recruitment of both monocytic CD172a+ cells and T lymphocytes to the corresponding EREC supernatants. Our data reveal a novel function of EHV1-gp2, tempering leukocyte migration to the URT, further indicating a sophisticated virus-mediated orchestration of leukocyte recruitment to the URT.
Highlights
Chemokines are a large family of low-molecular-weight proteins that belong to the cytokine superfamily
At 12 or 24 h p.i., EHV1-inoculated primary respiratory epithelial cells (ERECs) were treated with 10 μg brefeldin A (BFA) ml−1 to prevent chemokine secretion from the cell and to optimize CXCL9 and CXCL10 visualization by immunofluorescence staining
We demonstrated that the replication of both equine herpesvirus 1 (EHV1) variants activates the chemokine response to a greater (CXCL9) or lesser (CXCL10) extent in the respiratory epithelium
Summary
Chemokines are a large family of low-molecular-weight proteins that belong to the cytokine superfamily. It has become clear that specific chemokines and their receptors provide the molecular code responsible for the coordination of leukocyte trafficking [1, 2] Together with their highly recognized roles in cell migration, these small proteins have multiple other functional properties, including cell survival and proliferation [3]. Pathogen-associated molecular pattern (PAMP) receptors at the mucosal surfaces recognize viral products such as HSV1 gH/gL and gB glycoproteins, viral RNA and CpG motifs, resulting in signal transduction through the ancestral PAMP recognition pathways [8, 9] These signaling cascades induce the production of inflammatory chemokines either directly through nuclear factor kappa b (NF-κB) and mitogen-activated protein kinase (MAPK) activation and translocation to the nucleus, resulting in the transcription and translation of pro-inflammatory cytokines. Antigen recognition by specific lymphocytes drives chemokine expression, either directly or indirectly
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
