Possible roles of monocytes/macrophages in response to elephant endotheliotropic herpesvirus (EEHV) infections in Asian elephants (Elephas maximus)

Srivorakul, Saralee; Guntawang, Thunyamas; Kochagul, Varankpicha; Photichai, Kornravee; Sittisak, Tidaratt; Janyamethakul, Thittaya; Boonprasert, Khajohnpat; Khammesri, Siripat; Langkaphin, Warangkhana; Punyapornwithaya, Veerasak; Chuammitri, Phongsakorn; Thitaram, Chatchote; Pringproa, Kidsadagon

doi:10.1371/journal.pone.0222158

Cited by 20 publications

(27 citation statements)

References 55 publications

(95 reference statements)

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“…This study focused on the ability to measure cytokines at the protein level (i.e., secreted) as opposed to cytokine expression at the RNA level, which has been used to investigate tuberculosis [ 21 , 23 , 24 , 26 ] and EEHV [ 27 ] infection in Asian elephants previously. The main advantage of this approach is that we can utilize cryopreserved serum samples that are already collected for routine veterinary and management purposes, allowing a longitudinal perspective on changes in immune function required for a better understanding of physiological and pathological processes.…”

Section: Discussionmentioning

confidence: 99%

“…The immune response to infection can also be detected through altered cytokine production. For example, IFN-γ, TNF-α, and IL-10 expression is increased in Asian elephants seropositive for tuberculosis [ 26 ], and TNF-α and IFN-γ are upregulated in in vitro stimulated immune cells from elephants with EEHV [ 27 ]. In this study, an Asian elephant with a systemic infection exhibited elevated IL-10, IFN-γ, and TNF-α compared to paired non-clinical sample concentrations in the same individual.…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, the combination of cytokines produced can reflect the type and stage of the immune response [ 18 ], as well as provide prognostic information regarding the likelihood or progression of disease [ 19 , 20 ]. Some cytokine mRNAs have been characterized in Asian elephants [ 21 , 22 ] and studied previously [ 23 , 24 , 25 , 26 , 27 ]; however, measures of circulating protein concentrations through different pathological processes are lacking, as are typical values observed within a species or population to better interpret results.…”

Section: Introductionmentioning

confidence: 99%

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Serum Health Biomarkers in African and Asian Elephants: Value Ranges and Clinical Values Indicative of the Immune Response

Edwards

Miller

Siegal-Willott

et al. 2020

Animals

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Serum biomarkers indicative of inflammation and disease can provide useful information regarding host immune processes, responses to treatment and prognosis. The aims of this study were to assess the use of commercially available anti-equine reagents for the quantification of cytokines (tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), interleukins (IL) 2, 6, and 10) in African (Loxodonta africana, n = 125) and Asian (Elephas maximus, n = 104) elephants, and alongside previously validated anti-human reagents for acute-phase proteins (serum amyloid A and haptoglobin), calculate species-specific biomarker value ranges. In addition, we used opportunistically collected samples to investigate the concentrations of each biomarker during identified clinical cases of illness or injury, as a first step to understanding what biomarkers may be useful to managing elephant health. Immune biomarkers were each elevated above the calculated species-specific value ranges in at least one clinical case, but due to variability in both clinical and non-clinical samples, only serum amyloid A was significantly higher in clinical compared to non-clinical paired samples, with tendencies for higher TNF-α and IL-10. We also detected increased secretion of serum amyloid A and all five cytokines following routine vaccination of a single Asian elephant, indicating that these biomarkers can be beneficial for studying normal immune processes as well as pathology. This study indicates that assays developed with commercial reagents can be used to quantify health biomarkers in wildlife species and identifies several that warrant further investigation to elucidate immune responses to various pathologies.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Serum Health Biomarkers in African and Asian Elephants: Value Ranges and Clinical Values Indicative of the Immune Response

Edwards

Miller

Siegal-Willott

et al. 2020

Animals

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“…Furthermore, genes near Asian elephant-specific ARs were enriched for the GO term 'negative regulation of tumor necrosis factor-mediated signaling pathway' (q-value = 0.0448). While an enhanced apoptotic response to DNA damage can be a potential mechanism for cancer resistance in elephants 18,19 , increased apoptosis also can be associated with the upregulation of TNF-alpha especially in the setting of EEHV-infected Asian elephant PBMCs 36 . This suggests that regulatory elements may govern immunological differences between the two elephant species.…”

Section: Discussionmentioning

confidence: 99%

Elephant Genomes Elucidate Disease Defenses and Other Traits

Tollis

Ferris

Ms.

et al. 2020

Preprint

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Disease susceptibility and defense are important factors in conservation, particularly for elephants. We report that in addition to endotheliotropic herpesvirus and tuberculosis, Asian elephants are also more susceptible to cancer than African elephants. To determine mechanisms underlying elephant traits including disease resistance, we analyzed genomic datasets from multiple individuals and species. We report a draft genome assembly for the Asian elephant and an improved African elephant assembly. We found 862 and 1,017 potential regulatory elements in Asian and African elephants, respectively, that are enriched near 5,034 differentially expressed genes in peripheral blood mononuclear cells between the two species.These genes are enriched in immunity pathways, including tumor-necrosis factor which plays a role in the elephant response to endotheliotropic herpesvirus. Some elephant TP53 retrogenes are being maintained by purifying selection and may contribute to cancer resistance in elephants. Positive selection scans revealed genes that may control tusk development, memory, and somatic maintenance. Our study provides an example of how genomics can inform functional immunological studies, which may improve conservation and medical care for elephants and translate into human therapies.

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“…Similar to other herpesviruses, it has been speculated that EEHV is able to evade host immune responses and become persistent in infected elephants [22]. However, the cell types that are targeted by the virus during persistent infections remain to be determined [22].…”

Section: Introductionmentioning

confidence: 99%

Attempt to Isolate Elephant Endotheliotropic Herpesvirus (EEHV) Using a Continuous Cell Culture System

Photichai

Guntawang

Sittisak

et al. 2020

Animals

Self Cite

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Elephant endotheliotropic herpesvirus (EEHV) infection is known to cause acute fatal hemorrhagic disease, which has killed many young Asian elephants (Elephas maximus). Until recently, in vitro isolation and propagation of the virus have not been successful. This study aimed to isolate and propagate EEHV using continuous cell lines derived from human and/or animal origins. Human cell lines, including EA. hy926, A549, U937, RKO, SW620, HCT-116 and HT-29, and animal cell lines, including CT26.CL25 and sp2/0-Ag14, were investigated in this study. Mixed frozen tissue samples of the heart, lung, liver, spleen and kidney obtained from fatal EEHV1A- or EEHV4-infected cases were homogenized and used for cell inoculation. At 6, 24, 48 and 72 h post infection (hpi), EEHV-inoculated cells were observed for cytopathic effects (CPEs) or were assessed for EEHV infection by immunoperoxidase monolayer assay (IPMA) or quantitative PCR. The results were then compared to those of the mock-infected controls. Replication of EEHV in the tested cells was further determined by immunohistochemistry of cell pellets using anti-EEHV DNA polymerase antibodies or re-inoculated cells with supernatants obtained from passages 2 or 3 of the culture medium. The results reveal that no CPEs were observed in the tested cells, while immunolabeling for EEHV gB was observed in only U937 human myeloid leukemia cells. However, quantitation values of the EEHV terminase gene, as well as those of the EEHV gB or EEHV DNA polymerase proteins in U937 cells, gradually declined from passage 1 to passage 3. The findings of this study indicate that despite poor adaptation in U937 cells, this cell line displays promise and potential to be used for the isolation of EEHV1 and EEHV4 in vitro.

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Possible roles of monocytes/macrophages in response to elephant endotheliotropic herpesvirus (EEHV) infections in Asian elephants (Elephas maximus)

Cited by 20 publications

References 55 publications

Serum Health Biomarkers in African and Asian Elephants: Value Ranges and Clinical Values Indicative of the Immune Response

Serum Health Biomarkers in African and Asian Elephants: Value Ranges and Clinical Values Indicative of the Immune Response

Elephant Genomes Elucidate Disease Defenses and Other Traits

Attempt to Isolate Elephant Endotheliotropic Herpesvirus (EEHV) Using a Continuous Cell Culture System

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