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Article

Equine Herpesvirus Type 1 Modulates Cytokine and Chemokine Profiles of Mononuclear Cells for Efficient Dissemination to Target Organs

1
Institut für Virologie, Robert von Ostertag-Haus, Zentrum für Infektionsmedizin, Freie Universität Berlin, Robert-von-Ostertag-Straße 7-13, 14163 Berlin, Germany
2
Department of Medicine and Infectious Diseases, Faculty of Veterinary Medicine, Cairo University, 12211 Cairo, Egypt
3
Leibniz Institute of Molecular Pharmacology (FMP Berlin), Robert-Rössle-Str. 10, 13125 Berlin, Germany
4
Institut für Veterinäranatomie, Freie Universität Berlin, Koserstraße 20, 14195 Berlin, Germany
*
Author to whom correspondence should be addressed.
Viruses 2020, 12(9), 999; https://doi.org/10.3390/v12090999
Received: 10 August 2020 / Revised: 31 August 2020 / Accepted: 5 September 2020 / Published: 8 September 2020
(This article belongs to the Special Issue Animal Herpesviruses Pathogenesis and Immunity)
Equine herpesvirus type 1 (EHV-1) causes encephalomyelopathy and abortion, for which cell-associated viremia and subsequent virus transfer to and replication in endothelial cells (EC) are responsible and prerequisites. Viral and cellular molecules responsible for efficient cell-to-cell spread of EHV-1 between peripheral blood mononuclear cells (PBMC) and EC remain unclear. We have generated EHV-1 mutants lacking ORF1, ORF2, and ORF17 genes, either individually or in combination. Mutant viruses were analyzed for their replication properties in cultured equine dermal cells, PBMC infection efficiency, virus-induced changes in the PBMC proteome, and cytokine and chemokine expression profiles. ORF1, ORF2, and ORF17 are not essential for virus replication, but ORF17 deletion resulted in a significant reduction in plaque size. Deletion of ORF2 and ORF17 gene significantly reduced cell-to-cell virus transfer from virus-infected PBMC to EC. EHV-1 infection of PBMC resulted in upregulation of several pathways such as Ras signaling, oxidative phosphorylation, platelet activation and leukocyte transendothelial migration. In contrast, chemokine signaling, RNA degradation and apoptotic pathways were downregulated. Deletion of ORF1, ORF2 and ORF17 modulated chemokine signaling and MAPK pathways in infected PBMC, which may explain the impairment of virus spread between PBMC and EC. The proteomic results were further confirmed by chemokine assays, which showed that virus infection dramatically reduced the cytokine/chemokine release in infected PBMC. This study uncovers cellular proteins and pathways influenced by EHV-1 after PBMC infection and provide an important resource for EHV-1 pathogenesis. EHV-1-immunomodulatory genes could be potential targets for the development of live attenuated vaccines or therapeutics against virus infection. View Full-Text
Keywords: EHV-1; pathogenesis; flow chamber assay; endothelium; equine; PBMC EHV-1; pathogenesis; flow chamber assay; endothelium; equine; PBMC
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MDPI and ACS Style

Pavulraj, S.; Kamel, M.; Stephanowitz, H.; Liu, F.; Plendl, J.; Osterrieder, N.; Azab, W. Equine Herpesvirus Type 1 Modulates Cytokine and Chemokine Profiles of Mononuclear Cells for Efficient Dissemination to Target Organs. Viruses 2020, 12, 999. https://doi.org/10.3390/v12090999

AMA Style

Pavulraj S, Kamel M, Stephanowitz H, Liu F, Plendl J, Osterrieder N, Azab W. Equine Herpesvirus Type 1 Modulates Cytokine and Chemokine Profiles of Mononuclear Cells for Efficient Dissemination to Target Organs. Viruses. 2020; 12(9):999. https://doi.org/10.3390/v12090999

Chicago/Turabian Style

Pavulraj, Selvaraj, Mohamed Kamel, Heike Stephanowitz, Fan Liu, Johanna Plendl, Nikolaus Osterrieder, and Walid Azab. 2020. "Equine Herpesvirus Type 1 Modulates Cytokine and Chemokine Profiles of Mononuclear Cells for Efficient Dissemination to Target Organs" Viruses 12, no. 9: 999. https://doi.org/10.3390/v12090999

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