PMID- 31491031 OWN - NLM STAT- MEDLINE DCOM- 20200310 LR - 20200310 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 14 IP - 9 DP - 2019 TI - Possible roles of monocytes/macrophages in response to elephant endotheliotropic herpesvirus (EEHV) infections in Asian elephants (Elephas maximus). PG - e0222158 LID - 10.1371/journal.pone.0222158 [doi] LID - e0222158 AB - Elephant endotheliotropic herpesvirus-hemorrhagic disease (EEHV-HD) is the primary cause of acute, highly fatal, hemorrhagic diseases in young Asian elephants. Although monocytopenia is frequently observed in EEHV-HD cases, the role monocytes play in EEHV-disease pathogenesis is unknown. This study seeks to explain the responses of monocytes/macrophages in the pathogenesis of EEHV-HD. Samples of blood, frozen tissues, and formalin-fixed, paraffin-embedded (FFPE) tissues from EEHV1A-HD, EEHV4-HD, co-infected EEHV1A and 4-HD, and EEHV-negative calves were analyzed. Peripheral blood mononuclear cells (PBMCs) from the persistent EEHV4-infected and EEHV-negative calves were also studied. The results showed increased infiltration of Iba-1-positive macrophages in the inflamed tissues of the internal organs of elephant calves with EEHV-HD. In addition, cellular apoptosis also increased in the tissues of elephants with EEHV-HD, especially in the PBMCs, compared to the EEHV-negative control. In the PBMCs of persistent EEHV4-infected elephants, cytokine mRNA expression was high, particularly up-regulation of TNF-alpha and IFN-gamma. Moreover, viral particles were observed in the cytoplasm of the persistent EEHV4-infected elephant monocytes. Our study demonstrated for the first time that apoptosis of the PBMCs increased in cases of EEHV-HD. Furthermore, this study showed that monocytes may serve as a vehicle for viral dissemination during EEHV infection in Asian elephants. FAU - Srivorakul, Saralee AU - Srivorakul S AD - Veterinary Diagnostic Laboratory, Faculty of Veterinary Medicine, Chiang Mai University, Chiang Mai, Thailand. FAU - Guntawang, Thunyamas AU - Guntawang T AD - Department of Veterinary Biosciences and Veterinary Public Health, Faculty of Veterinary Medicine, Chiang Mai University, Chiang Mai, Thailand. FAU - Kochagul, Varankpicha AU - Kochagul V AD - Veterinary Diagnostic Laboratory, Faculty of Veterinary Medicine, Chiang Mai University, Chiang Mai, Thailand. FAU - Photichai, Kornravee AU - Photichai K AD - Veterinary Diagnostic Laboratory, Faculty of Veterinary Medicine, Chiang Mai University, Chiang Mai, 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, Thailand. FAU - Janyamethakul, Thittaya AU - Janyamethakul T AD - Patara Elephant Farm, Hang Dong, Chiang Mai, Thailand. FAU - Boonprasert, Khajohnpat AU - Boonprasert K AD - Center of Excellence in Elephant and Wildlife Research, Chiang Mai University, Chiang Mai, Thailand. FAU - Khammesri, Siripat AU - Khammesri S AD - Maesa Elephant Camp, Mae Rim, Chiang Mai, Thailand. FAU - Langkaphin, Warangkhana AU - Langkaphin W AD - National Elephant Institute, Forest Industry Organization, Lampang, Thailand. FAU - Punyapornwithaya, Veerasak AU - Punyapornwithaya V AD - Department of Food Animal Clinic, Faculty of Veterinary Medicine, Chiang Mai University, Chiang Mai, Thailand. FAU - Chuammitri, Phongsakorn AU - Chuammitri P AD - Department of Veterinary Biosciences and Veterinary Public Health, Faculty of Veterinary Medicine, Chiang Mai University, Chiang Mai, Thailand. FAU - Thitaram, Chatchote AU - Thitaram C AUID- ORCID: 0000-0001-9319-5596 AD - Center of Excellence in Elephant and Wildlife Research, Chiang Mai University, Chiang Mai, Thailand. AD - Department of Companion Animals and Wildlife Clinics, Faculty of Veterinary Medicine, Chiang Mai University, Chiang Mai, Thailand. FAU - Pringproa, Kidsadagon AU - Pringproa K AUID- ORCID: 0000-0001-7291-1100 AD - Department of Veterinary Biosciences and Veterinary Public Health, Faculty of Veterinary Medicine, Chiang Mai University, Chiang Mai, Thailand. AD - Center of Excellence in Elephant and Wildlife Research, Chiang Mai University, Chiang Mai, Thailand. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190906 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Cytokines) RN - 0 (RNA, Messenger) SB - IM MH - Animals MH - Apoptosis MH - Cytokines/genetics MH - Elephants/*virology MH - Female MH - Gene Expression Regulation MH - Herpesviridae/*physiology MH - Herpesviridae Infections/genetics/*immunology MH - Macrophages/*cytology MH - Male MH - Monocytes/*cytology MH - RNA, Messenger/genetics PMC - PMC6730851 COIS- The authors have declared that no competing interests exist. EDAT- 2019/09/07 06:00 MHDA- 2020/03/11 06:00 PMCR- 2019/09/06 CRDT- 2019/09/07 06:00 PHST- 2019/03/29 00:00 [received] PHST- 2019/08/22 00:00 [accepted] PHST- 2019/09/07 06:00 [entrez] PHST- 2019/09/07 06:00 [pubmed] PHST- 2020/03/11 06:00 [medline] PHST- 2019/09/06 00:00 [pmc-release] AID - PONE-D-19-08095 [pii] AID - 10.1371/journal.pone.0222158 [doi] PST - epublish SO - PLoS One. 2019 Sep 6;14(9):e0222158. doi: 10.1371/journal.pone.0222158. eCollection 2019.