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Investigation of haematologic, inflammatory, and haemostatic in horses experimentally infected with African horse sickness virus
Thesis (PhD)--University of Pretoria, 2023.
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University of Pretoria
2024
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| _version_ | 1867613722470514688 |
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| access_status_str | Open Access |
| author2 | Goddard, Amelia |
| author_browse | Goddard, Amelia |
| author_facet | Goddard, Amelia |
| collection | Thesis |
| dc_rights_str_mv | © 2021 University of Pretoria. All rights reserved. The copyright in this work vests in the University of Pretoria. No part of this work may be reproduced or transmitted in any form or by any means, without the prior written permission of the University of Pretoria. |
| description | Thesis (PhD)--University of Pretoria, 2023. |
| format | Thesis |
| id | oai:repository.up.ac.za:2263/98451 |
| institution | University of Pretoria (South Africa) |
| language | English |
| last_indexed | 2026-06-10T12:40:40.078Z |
| license_str | Other — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from UPSpace — University of Pretoria Institutional Repository |
| publishDate | 2024 |
| publishDateRange | 2024 |
| publishDateSort | 2024 |
| publisher | University of Pretoria |
| publisherStr | University of Pretoria |
| record_format | dspace |
| source_str | UPSpace — University of Pretoria Institutional Repository |
| spelling | oai:repository.up.ac.za:2263/98451 Investigation of haematologic, inflammatory, and haemostatic in horses experimentally infected with African horse sickness virus Goddard, Amelia tine.schliewert@web.de Hooijberg, Emma Henriette Schliewert, Eva-Christina UCTD Infectious diseases Equine Immunology Immune interference Thesis (PhD)--University of Pretoria, 2023. African horse sickness (AHS) is an infectious disease affecting equids. It is caused by the African horse sickness virus (AHSV), a double-stranded RNA Orbivirus with 9 different serotypes which is transmitted by insect vectors, particularly Culicoides midges and is endemic in sub-Saharan Africa. Infection with AHSV results in one of four disease forms, the pulmonary (“dunkop”), cardiac (“dikkop”), mixed, and fever form and morbidity and mortality ranges of up to 100% are described in naïve horses. Clinical signs such as dyspnoea, fever, haemorrhages, and pulmonary oedema are thought to be reflective of inflammation and endothelial damage due to viral replication in the vascular endothelial cells. To date, the understanding of the underlying pathology is marginal, and no therapy has been recognized as effective. The enzootic virus has important implications on animal welfare, the equine industry and the local economy of rural communities which depends on working equids. Given the limited knowledge of the inflammatory response to infection with AHSV and the resulting haematological changes and alterations in haemostasis, the broad objectives of this study were to 1) evaluate the haematological changes and changes in acute phase reactants; 2) describe the changes in selected cytokines; and 3) characterize the haemostatic changes occurring in horses experimentally infected with AHSV. The study was designed as a prospective, longitudinal, experimental study which included four healthy AHS-susceptible Boerperd cross horses that had tested negative for AHSV group-specific antibodies using a commercial competitive enzyme-linked immunosorbent assay (ELISA) against all nine AHSV serotypes. These horses were infected intravenously with low passage mouse brain suspension (5 mL) that contained at least 105 mouse infective doses/mL of virulent AHSV serotypes. Each horse was inoculated with a different AHS serovar: horse 1, AHSV-2 (horse origin); horse 2, AHSV-4 (horse origin); horse 3, AHSV-6 (horse origin) and horse 4, AHSV-6 (dog origin). All horses developed severe clinical signs typical of AHS post infection and were humanely euthanized. All horses developed significant haemoconcentration in the late stages of the disease. Significant thrombocytopenia with increased markers of platelet activation developed; however, changes in leukocytes and acute phase reactants serum amyloid A (SAA) and serum iron were significant but not considered clinically relevant. This suggested possible derangements in the host’s immune response which contribute to the observed dampened immune response in reaction to the inflammatory stimuli triggered by the virus. To further elucidate the immune response to infection with AHSV, selected plasma cytokines interleukin (IL)-1α, IL-2, IL-6, IL-8, IL-10, IL-12, IL-17, interferon (IFN)-, tumour necrosis factor (TNF)-α, and monocyte chemoattractant protein (MCP)-1, which represent mediators of both innate and adaptive immunity pathways, were evaluated throughout the course of the disease. Unexpectedly, an almost complete absence of proinflammatory cytokines in blood was observed, as only TNF-α increased in the final stages of the disease while an increase in IL-10, considered an anti-inflammatory cytokine, was predominant. This correlates with the previous findings of a mild acute phase response and mild haematological changes as these responses are mediated by cytokines. The lack of a significant cytokine response could indicate viral immune evasion mechanisms. In Orbiviruses, in vivo studies have documented inhibition of the immune response by the virus – specifically of IFN and Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathways and this is a likely cause of the lack of a proinflammatory response. Horse infected with AHSV develop haemorrhages; this finding is thought to be mainly due to the endothelial damage caused directly by viral replication in endothelial cells. It is now understood that inflammation and haemostasis are closely integrated, and inflammatory cytokines activate haemostatic pathways by increasing tissue factor expression on circulating endothelial cells, monocytes and macrophages. Specifically, horses developed overt disseminated intravascular coagulation (DIC), a consumptive coagulopathy, and clinical signs of bleeding, and procoagulant activation, inhibition of anticoagulants and fibrinolysis was detected on both traditional coagulation tests and viscoelastic tests. Given the lack of proinflammatory cytokines, inflammatory activation of the haemostatic pathways is likely secondary while endothelial damage is the probable primary trigger for activation of haemostasis. The findings of this study further elucidate the pathogenesis of the AHSV. The results suggest that AHSV is capable of interfering with the innate immune response, possibly via interference with the Janus kinase/signal transducers and activators of transcription (JAK/STAT) signalling pathways or promyelocytic leukaemia nuclear bodies (PML-NBs), while simultaneously initiating haemostatic pathways, most likely via endothelial damage, and causing overt DIC. Early identification of haemostatic derangements allows for earlier intervention which may improve outcome. Recognition of the virus’s capability to interfere with the innate immune system may be used to develop new treatment strategies, including direct cytokine or antibody therapy to improve the development of more effective vaccines. Companion Animal Clinical Studies PhD Unrestricted Faculty of Veterinary Science 2024-10-02T13:07:59Z 2024-10-02T13:07:59Z 2024-04 2023 Thesis * A2024 http://hdl.handle.net/2263/98451 en © 2021 University of Pretoria. All rights reserved. The copyright in this work vests in the University of Pretoria. No part of this work may be reproduced or transmitted in any form or by any means, without the prior written permission of the University of Pretoria. application/pdf University of Pretoria |
| spellingShingle | UCTD Infectious diseases Equine Immunology Immune interference Investigation of haematologic, inflammatory, and haemostatic in horses experimentally infected with African horse sickness virus |
| title | Investigation of haematologic, inflammatory, and haemostatic in horses experimentally infected with African horse sickness virus |
| title_full | Investigation of haematologic, inflammatory, and haemostatic in horses experimentally infected with African horse sickness virus |
| title_fullStr | Investigation of haematologic, inflammatory, and haemostatic in horses experimentally infected with African horse sickness virus |
| title_full_unstemmed | Investigation of haematologic, inflammatory, and haemostatic in horses experimentally infected with African horse sickness virus |
| title_short | Investigation of haematologic, inflammatory, and haemostatic in horses experimentally infected with African horse sickness virus |
| title_sort | investigation of haematologic inflammatory and haemostatic in horses experimentally infected with african horse sickness virus |
| topic | UCTD Infectious diseases Equine Immunology Immune interference |
| url | http://hdl.handle.net/2263/98451 |