Distinct transcriptional responses to fatal Ebola virus infection in cynomolgus and rhesus macaques suggest species-specific immune responses.
Distinct transcriptional responses to fatal Ebola virus infection in cynomolgus and rhesus macaques suggest species-specific immune responses.
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DOI：
10.1080/22221751.2021.1942229
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发表时间：
2021-12
影响因子：
13.2
通讯作者：
Messaoudi I
中科院分区：
文献类型：
--
作者：
Pinski AN;Maroney KJ;Marzi A;Messaoudi I
埃博拉病毒（EBOV）是丝状病毒科（Filoviridae）内的负单链RNA病毒，并且是埃博拉病毒病（EVD）的病原体。非人灵长类动物（NHP），包括食蟹猴和恒河猴，被认为是研究EBOV发病机制的金标准动物模型。然而，尽管具有显著的遗传相似性（>90%），但NHP物种在EBOV感染后显示出不同的临床表现，特别是疾病进展延迟10 - 1-2天。因此，治疗剂的评价通常在恒河猴中进行，而食蟹猴用于确定预防性治疗（特别是疫苗）的功效。这一观察结果与报道的猴水痘病毒、甲型流感病毒和SARS-CoV-2感染后这两种NHP之间疾病严重程度和宿主反应的差异一致。然而，病毒感染后这些不同结果的分子基础仍然不清楚。在这项研究中，我们比较了已发表的转录谱获得食蟹猴和恒河猴感染EBOV-Makona几内亚C 07使用双变量和回归分析，阐明宿主反应的差异。我们报告了一个共同的核心差异表达基因（DEG）的存在，反映EVD的病理，包括异常炎症，淋巴细胞减少症，凝血功能障碍。然而，两种猕猴物种之间的变化幅度不同。这些发现表明，EVD在这两个物种的差异性临床表现是由改变转录反应介导的。
Ebola virus (EBOV) is a negative single-stranded RNA virus within the Filoviridae family and the causative agent of Ebola virus disease (EVD). Nonhuman primates (NHPs), including cynomolgus and rhesus macaques, are considered the gold standard animal model to interrogate mechanisms of EBOV pathogenesis. However, despite significant genetic similarity (>90%), NHP species display different clinical presentation following EBOV infection, notably a ∼1–2 days delay in disease progression. Consequently, evaluation of therapeutics is generally conducted in rhesus macaques, whereas cynomolgus macaques are utilized to determine efficacy of preventative treatments, notably vaccines. This observation is in line with reported differences in disease severity and host responses between these two NHP following infection with simian varicella virus, influenza A and SARS-CoV-2. However, the molecular underpinnings of these differential outcomes following viral infections remain poorly defined. In this study, we compared published transcriptional profiles obtained from cynomolgus and rhesus macaques infected with the EBOV-Makona Guinea C07 using bivariate and regression analyses to elucidate differences in host responses. We report the presence of a shared core of differentially expressed genes (DEGs) reflecting EVD pathology, including aberrant inflammation, lymphopenia, and coagulopathy. However, the magnitudes of change differed between the two macaque species. These findings suggest that the differential clinical presentation of EVD in these two species is mediated by altered transcriptional responses.
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影响因子：
3.7
作者：
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影响因子：
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影响因子：
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