dc.contributor.author
Pavulraj, Selvaraj
dc.contributor.author
Kamel, Mohamed
dc.contributor.author
Stephanowitz, Heike
dc.contributor.author
Liu, Fan
dc.contributor.author
Plendl, Johanna
dc.contributor.author
Osterrieder, Nikolaus
dc.contributor.author
Azab, Walid
dc.date.accessioned
2020-11-25T10:17:53Z
dc.date.available
2020-11-25T10:17:53Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/28955
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-28705
dc.description.abstract
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.
en
dc.format.extent
26 Seiten
dc.rights.uri
https://creativecommons.org/licenses/by/4.0/
dc.subject
pathogenesis
en
dc.subject
flow chamber assay
en
dc.subject.ddc
600 Technik, Medizin, angewandte Wissenschaften::630 Landwirtschaft::630 Landwirtschaft und verwandte Bereiche
dc.title
Equine Herpesvirus Type 1 Modulates Cytokine and Chemokine Profiles of Mononuclear Cells for Efficient Dissemination to Target Organs
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation.articlenumber
999
dcterms.bibliographicCitation.doi
10.3390/v12090999
dcterms.bibliographicCitation.journaltitle
Viruses
dcterms.bibliographicCitation.number
9
dcterms.bibliographicCitation.originalpublishername
MDPI
dcterms.bibliographicCitation.volume
12
dcterms.bibliographicCitation.url
https://doi.org/10.3390/v12090999
refubium.affiliation
Veterinärmedizin
refubium.affiliation.other
Institut für Virologie
refubium.note.author
Die Publikation wurde aus Open Access Publikationsgeldern der Freien Universität Berlin gefördert.
refubium.resourceType.isindependentpub
no
dcterms.accessRights.openaire
open access
dcterms.isPartOf.eissn
1999-4915
refubium.resourceType.provider
WoS-Alert