PMID- 34155304 OWN - NLM STAT- MEDLINE DCOM- 20211108 LR - 20211108 IS - 2045-2322 (Electronic) IS - 2045-2322 (Linking) VI - 11 IP - 1 DP - 2021 Jun 21 TI - Pathogenesis of hemorrhagic disease caused by elephant endotheliotropic herpesvirus (EEHV) in Asian elephants (Elephas maximus). PG - 12998 LID - 10.1038/s41598-021-92393-8 [doi] LID - 12998 AB - Elephant endotheliotropic herpesvirus-hemorrhagic disease (EEHV-HD) is an acute fatal disease in elephants. Despite the fact that the underlying pathogenesis of EEHV-HD has been proposed, it remains undetermined as to what mechanisms drive these hemorrhagic and edematous lesions. In the present study, we have investigated and explained the pathogenesis of acute EEHV-HD using blood profiles of EEHV-HD and EEHV-infected cases, hematoxylin and eosin (H&E) stain, special stains, immunohistochemistry, quantitative polymerase chain reaction (PCR) and reverse transcriptase polymerase chain reaction (RT-PCR). It was found that EEHV genomes were predominantly detected in various internal organs of EEHV-HD cases. Damage to endothelial cells, vasculitis and vascular thrombosis of the small blood vessels were also predominantly observed. Increases in platelet endothelial cell adhesion molecules-1 (PECAM-1)- and von Willebrand factor (vWF)-immunolabeling positive cells were significantly noticed in injured blood vessels. The expression of pro-inflammatory cytokine mRNA was significantly up-regulated in EEHV-HD cases when compared to EEHV-negative controls. We have hypothesized that this could be attributed to the systemic inflammation and disruption of small blood vessels, followed by the disseminated intravascular coagulopathy that enhanced hemorrhagic and edematous lesions in EEHV-HD cases. Our findings have brought attention to the potential application of effective preventive and therapeutic protocols to treat EEHV infection in Asian elephants. FAU - Guntawang, Thunyamas AU - Guntawang T AD - Department of Veterinary Biosciences and Veterinary Public Health, Faculty of Veterinary Medicine, Chiang Mai University, Chiang Mai, 50100, Thailand. FAU - Sittisak, Tidaratt AU - Sittisak T AD - Department of Veterinary Biosciences and Veterinary Public Health, Faculty of Veterinary Medicine, Chiang Mai University, Chiang Mai, 50100, Thailand. FAU - Kochagul, Varankpicha AU - Kochagul V AD - Veterinary Diagnostic Laboratory, Faculty of Veterinary Medicine, Chiang Mai University, Chiang Mai, 50100, Thailand. FAU - Srivorakul, Saralee AU - Srivorakul S AD - Veterinary Diagnostic Laboratory, Faculty of Veterinary Medicine, Chiang Mai University, Chiang Mai, 50100, Thailand. FAU - Photichai, Kornravee AU - Photichai K AD - Veterinary Diagnostic Laboratory, Faculty of Veterinary Medicine, Chiang Mai University, Chiang Mai, 50100, Thailand. FAU - Boonsri, Kittikorn AU - Boonsri K AD - Veterinary Diagnostic Laboratory, Faculty of Veterinary Medicine, Chiang Mai University, Chiang Mai, 50100, Thailand. FAU - Janyamethakul, Thittaya AU - Janyamethakul T AD - Patara Elephant Farm, Hang Dong, Chiang Mai, 50230, Thailand. FAU - Boonprasert, Khajohnpat AU - Boonprasert K AD - Center of Excellence in Elephant and Wildlife Research, Chiang Mai University, Chiang Mai, 50100, Thailand. FAU - Langkaphin, Warangkhana AU - Langkaphin W AD - National Elephant Institute, Forest Industry Organization, Lampang, 52190, Thailand. FAU - Thitaram, Chatchote AU - Thitaram C AD - Center of Excellence in Elephant and Wildlife Research, Chiang Mai University, Chiang Mai, 50100, Thailand. AD - Department of Companion Animals and Wildlife Clinics, Faculty of Veterinary Medicine, Chiang Mai University, Chiang Mai, 50100, Thailand. FAU - Pringproa, Kidsadagon AU - Pringproa K AD - Department of Veterinary Biosciences and Veterinary Public Health, Faculty of Veterinary Medicine, Chiang Mai University, Chiang Mai, 50100, Thailand. kidsadagon.p@cmu.ac.th. AD - Center of Excellence in Elephant and Wildlife Research, Chiang Mai University, Chiang Mai, 50100, Thailand. kidsadagon.p@cmu.ac.th. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20210621 PL - England TA - Sci Rep JT - Scientific reports JID - 101563288 RN - 0 (Biomarkers) RN - 0 (Blood Coagulation Factors) RN - 0 (Cytokines) SB - IM MH - Animal Diseases/*diagnosis/*etiology MH - Animals MH - Biomarkers MH - Biopsy MH - Blood Coagulation MH - Blood Coagulation Factors MH - Blood Coagulation Tests MH - Capillary Permeability MH - Cytokines/genetics/metabolism MH - Disease Susceptibility MH - *Elephants MH - Hemorrhage/*diagnosis/*etiology MH - Herpesviridae/*physiology MH - Herpesviridae Infections/*veterinary MH - Immunohistochemistry MH - Models, Biological PMC - PMC8217522 COIS- The authors declare no competing interests. EDAT- 2021/06/23 06:00 MHDA- 2021/11/09 06:00 PMCR- 2021/06/21 CRDT- 2021/06/22 06:22 PHST- 2021/03/15 00:00 [received] PHST- 2021/06/10 00:00 [accepted] PHST- 2021/06/22 06:22 [entrez] PHST- 2021/06/23 06:00 [pubmed] PHST- 2021/11/09 06:00 [medline] PHST- 2021/06/21 00:00 [pmc-release] AID - 10.1038/s41598-021-92393-8 [pii] AID - 92393 [pii] AID - 10.1038/s41598-021-92393-8 [doi] PST - epublish SO - Sci Rep. 2021 Jun 21;11(1):12998. doi: 10.1038/s41598-021-92393-8.