Center for Species Survival, Smithsonian's National Zoological Park and Conservation Biology Institute, Front Royal, VA, United States of America.
National Elephant Herpesvirus Laboratory, Smithsonian's National Zoological Park and Conservation Biology Institute, Washington, DC, United States of America.
PLoS One. 2021 Nov 18;16(11):e0252175. doi: 10.1371/journal.pone.0252175. eCollection 2021.
Hemorrhagic disease (HD) caused by a group of elephant endotheliotropic herpesviruses (EEHV) is one of the leading causes of death for young elephants in human care. These viruses are widespread and typically persist latently in adult elephants with no negative effects; however, in juvenile Asian and more recently young African elephants, the onset of disease can be rapid and the mortality rate high. Measuring biomarkers associated with the immune response could be beneficial to understanding underlying disease processes, as well as the management of infection and HD. The goal of this study was to measure acute phase proteins and cytokines in serum collected from elephants infected with EEHV (13 Asian and 1 African) and compare concentrations according to presence, severity and outcome of disease. Serum amyloid A (SAA) and haptoglobin (HP) were higher in elephants with EEHV viremia than those without; concentrations increased with increasing viral load, and were higher in fatal cases compared to those that survived. In Asian elephants, SAA was also higher during EEHV1 viremia compared to EEHV5. Cytokine concentrations were typically low, and no statistical differences existed between groups. However, in individuals with detectable levels, longitudinal profiles indicated changes in tumor necrosis factor alpha (TNF-α) and interleukin-2 (IL-2) that may reflect an immune response to EEHV infection. However, the overall low concentrations detected using previously validated assays do not support the presence of a 'cytokine storm' and suggest more work is needed to understand if sub-optimal immune responses could be involved in disease progression. These results highlight the potential benefit of measuring circulating biomarker concentrations, such as APPs and cytokines, to improve our understanding of EEHV viremia and HD, assist with monitoring the progression of disease and determining the impact of interventions.
出血性疾病（HD）是由一组大象内皮细胞疱疹病毒（EEHV）引起的，是人类饲养的幼象死亡的主要原因之一。这些病毒广泛存在，通常在成年大象中潜伏存在而没有负面影响；然而，在幼年亚洲象和最近的年轻非洲象中，疾病的发作可能很快，死亡率很高。测量与免疫反应相关的生物标志物可能有助于了解潜在的疾病过程，以及感染和 HD 的管理。本研究的目的是测量感染 EEHV 的大象（13 头亚洲象和 1 头非洲象）血清中的急性期蛋白和细胞因子，并根据疾病的存在、严重程度和结果比较浓度。血清淀粉样蛋白 A（SAA）和触珠蛋白（HP）在感染 EEHV 的大象中高于未感染的大象；浓度随病毒载量的增加而增加，在致命病例中高于存活病例。在亚洲象中，在 EEHV1 血症期间 SAA 也高于 EEHV5。细胞因子浓度通常较低，组间无统计学差异。然而，在可检测到水平的个体中，纵向分析表明肿瘤坏死因子α（TNF-α）和白细胞介素 2（IL-2）的变化，这可能反映了对 EEHV 感染的免疫反应。然而，使用先前验证的测定法检测到的总体低浓度并不支持存在“细胞因子风暴”，并表明需要做更多的工作来了解是否亚最佳免疫反应可能涉及疾病进展。这些结果强调了测量循环生物标志物浓度（如 APP 和细胞因子）的潜在益处，以提高我们对 EEHV 血症和 HD 的理解，协助监测疾病的进展并确定干预措施的影响。
