@article{10.1371/journal.pone.0222158, doi = {10.1371/journal.pone.0222158}, author = {Srivorakul, Saralee AND Guntawang, Thunyamas AND Kochagul, Varankpicha AND Photichai, Kornravee AND Sittisak, Tidaratt AND Janyamethakul, Thittaya AND Boonprasert, Khajohnpat AND Khammesri, Siripat AND Langkaphin, Warangkhana AND Punyapornwithaya, Veerasak AND Chuammitri, Phongsakorn AND Thitaram, Chatchote AND Pringproa, Kidsadagon}, journal = {PLOS ONE}, publisher = {Public Library of Science}, title = {Possible roles of monocytes/macrophages in response to elephant endotheliotropic herpesvirus (EEHV) infections in Asian elephants (Elephas maximus)}, year = {2019}, month = {09}, volume = {14}, url = {https://doi.org/10.1371/journal.pone.0222158}, pages = {1-18}, abstract = {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-α and IFN-γ. 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.}, number = {9}, }