MODULATION OF INFLAMMATORY CYTOKINE, CHEMOKINE, AND TOLL-LIKE RECEPTOR GENES AND TRANSCRIPTOME ANALYSIS OF EQUINE ENDOTHELIAL CELLS FOLLOWING INFECTION WITH EQUID HERPESVIRUS-1, AND EQUINE ARTERITIS VIRUS.
EHV-1 is a double-stranded DNA virus whereas EAV is a positive sense, single-stranded RNA virus. Therefore, genetically, they are very different from one another. However, both these viruses are endotheliotropic and thus, infect and replicates in equine endothelial cells resulting in vasculitis. Vas...
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ndltd-uky.edu-oai-uknowledge.uky.edu-gluck_etds-10472019-10-16T04:27:58Z MODULATION OF INFLAMMATORY CYTOKINE, CHEMOKINE, AND TOLL-LIKE RECEPTOR GENES AND TRANSCRIPTOME ANALYSIS OF EQUINE ENDOTHELIAL CELLS FOLLOWING INFECTION WITH EQUID HERPESVIRUS-1, AND EQUINE ARTERITIS VIRUS. Dunuwille, Saranajith Wangisa EHV-1 is a double-stranded DNA virus whereas EAV is a positive sense, single-stranded RNA virus. Therefore, genetically, they are very different from one another. However, both these viruses are endotheliotropic and thus, infect and replicates in equine endothelial cells resulting in vasculitis. Vasculitis is central to the pathogenesis of these two viruses. Thus, the main objective of this thesis was to investigate the inflammatory and innate immune responses of EECs that contribute towards the development of vasculitis following infection with EHV-1 and EAV in-vitro. Since proinflammatory cytokines and chemokines produced by endothelial cells play a significant role in the development of vasculitis, we investigated their gene expression as well as secretion. Results from this study showed that the proinflammatory response of EECs induced by EAV is relatively less when compared with the corresponding results from EHV-1 infected EECs. Furthermore, EAV elicits a lower type I interferon response in EECs when compared with EHV-1. Further investigations revealed an active role played by TLR 3 in inducing the proinflammatory response in EHV-1 infected EECs during the first 6 hours of infection but not in EAV infected EECs. Analyzing the whole transcriptome of EHV-1 and EAV infected EECs revealed a complex pattern of gene regulation and cellular pathways related to cellular immune, inflammatory and apoptotic responses. Finally, we investigated host genetic factors associated with EHV-1 induced myeloencephalopathy but found no evidence for a recessive allele influencing the development of EHM following EHV-1 infection for any genetic locus was identified. However, more complex host-pathogen interactions are possible. 2019-01-01T08:00:00Z text application/pdf https://uknowledge.uky.edu/gluck_etds/44 https://uknowledge.uky.edu/cgi/viewcontent.cgi?article=1047&context=gluck_etds Theses and Dissertations--Veterinary Science UKnowledge EHV-1 EAV TLR3 Type I interferons RT-qPCR Luminex si-RNA RNAi GWAS RNA-seq Virology |
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EHV-1 EAV TLR3 Type I interferons RT-qPCR Luminex si-RNA RNAi GWAS RNA-seq Virology |
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EHV-1 EAV TLR3 Type I interferons RT-qPCR Luminex si-RNA RNAi GWAS RNA-seq Virology Dunuwille, Saranajith Wangisa MODULATION OF INFLAMMATORY CYTOKINE, CHEMOKINE, AND TOLL-LIKE RECEPTOR GENES AND TRANSCRIPTOME ANALYSIS OF EQUINE ENDOTHELIAL CELLS FOLLOWING INFECTION WITH EQUID HERPESVIRUS-1, AND EQUINE ARTERITIS VIRUS. |
description |
EHV-1 is a double-stranded DNA virus whereas EAV is a positive sense, single-stranded RNA virus. Therefore, genetically, they are very different from one another. However, both these viruses are endotheliotropic and thus, infect and replicates in equine endothelial cells resulting in vasculitis. Vasculitis is central to the pathogenesis of these two viruses. Thus, the main objective of this thesis was to investigate the inflammatory and innate immune responses of EECs that contribute towards the development of vasculitis following infection with EHV-1 and EAV in-vitro. Since proinflammatory cytokines and chemokines produced by endothelial cells play a significant role in the development of vasculitis, we investigated their gene expression as well as secretion. Results from this study showed that the proinflammatory response of EECs induced by EAV is relatively less when compared with the corresponding results from EHV-1 infected EECs. Furthermore, EAV elicits a lower type I interferon response in EECs when compared with EHV-1. Further investigations revealed an active role played by TLR 3 in inducing the proinflammatory response in EHV-1 infected EECs during the first 6 hours of infection but not in EAV infected EECs. Analyzing the whole transcriptome of EHV-1 and EAV infected EECs revealed a complex pattern of gene regulation and cellular pathways related to cellular immune, inflammatory and apoptotic responses. Finally, we investigated host genetic factors associated with EHV-1 induced myeloencephalopathy but found no evidence for a recessive allele influencing the development of EHM following EHV-1 infection for any genetic locus was identified. However, more complex host-pathogen interactions are possible. |
author |
Dunuwille, Saranajith Wangisa |
author_facet |
Dunuwille, Saranajith Wangisa |
author_sort |
Dunuwille, Saranajith Wangisa |
title |
MODULATION OF INFLAMMATORY CYTOKINE, CHEMOKINE, AND TOLL-LIKE RECEPTOR GENES AND TRANSCRIPTOME ANALYSIS OF EQUINE ENDOTHELIAL CELLS FOLLOWING INFECTION WITH EQUID HERPESVIRUS-1, AND EQUINE ARTERITIS VIRUS. |
title_short |
MODULATION OF INFLAMMATORY CYTOKINE, CHEMOKINE, AND TOLL-LIKE RECEPTOR GENES AND TRANSCRIPTOME ANALYSIS OF EQUINE ENDOTHELIAL CELLS FOLLOWING INFECTION WITH EQUID HERPESVIRUS-1, AND EQUINE ARTERITIS VIRUS. |
title_full |
MODULATION OF INFLAMMATORY CYTOKINE, CHEMOKINE, AND TOLL-LIKE RECEPTOR GENES AND TRANSCRIPTOME ANALYSIS OF EQUINE ENDOTHELIAL CELLS FOLLOWING INFECTION WITH EQUID HERPESVIRUS-1, AND EQUINE ARTERITIS VIRUS. |
title_fullStr |
MODULATION OF INFLAMMATORY CYTOKINE, CHEMOKINE, AND TOLL-LIKE RECEPTOR GENES AND TRANSCRIPTOME ANALYSIS OF EQUINE ENDOTHELIAL CELLS FOLLOWING INFECTION WITH EQUID HERPESVIRUS-1, AND EQUINE ARTERITIS VIRUS. |
title_full_unstemmed |
MODULATION OF INFLAMMATORY CYTOKINE, CHEMOKINE, AND TOLL-LIKE RECEPTOR GENES AND TRANSCRIPTOME ANALYSIS OF EQUINE ENDOTHELIAL CELLS FOLLOWING INFECTION WITH EQUID HERPESVIRUS-1, AND EQUINE ARTERITIS VIRUS. |
title_sort |
modulation of inflammatory cytokine, chemokine, and toll-like receptor genes and transcriptome analysis of equine endothelial cells following infection with equid herpesvirus-1, and equine arteritis virus. |
publisher |
UKnowledge |
publishDate |
2019 |
url |
https://uknowledge.uky.edu/gluck_etds/44 https://uknowledge.uky.edu/cgi/viewcontent.cgi?article=1047&context=gluck_etds |
work_keys_str_mv |
AT dunuwillesaranajithwangisa modulationofinflammatorycytokinechemokineandtolllikereceptorgenesandtranscriptomeanalysisofequineendothelialcellsfollowinginfectionwithequidherpesvirus1andequinearteritisvirus |
_version_ |
1719269397649948672 |