Seeded Amplification of Chronic Wasting Disease Prions in Nasal Brushings and Recto-anal Mucosa-Associated Lymphoid Tissues from Elk by Real-Time Quaking-Induced Conversion
Seeded Amplification of Chronic Wasting Disease Prions in Nasal Brushings and Recto-anal Mucosa-Associated Lymphoid Tissues from Elk by Real-Time Quaking-Induced Conversion
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DOI：
10.1128/jcm.02700-15
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发表时间：
2016-04-01
影响因子：
9.4
通讯作者：
Richt, Juergen A.
中科院分区：
文献类型：
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作者：
Haley, Nicholas J.;Siepker, Chris;Richt, Juergen A.
慢性消耗病（CWD）是一种鹿的传染性海绵状脑病，大约50年前在科罗拉多和怀俄明州首次发现，此后在北美和大韩民国都发现了这种疾病。这种疾病的蔓延使得开发灵敏的诊断化验和死前取样技术对于减缓其传播至关重要;在对大型或受保护畜群进行迁移/再引入或流行率研究时尤其如此，在这些情况下，可能禁止进行种群灭绝。本研究评价了直肠肛门粘膜相关淋巴组织（RAMALT）活检标本和死前采集的鼻刷的实时震动诱导转化（RT-QuIC）试验的灵敏度。这些结果进行了比较，免疫组织化学（IHC）分析的结果，生前和死后样本。RAMALT样本采集自养殖和自由放养的落基山麋鹿（马鹿nelsoni; n = 323），鼻刷样本采集自这些动物的亚群（n = 205）。我们假设RT-QuIC的灵敏度与RAMALT的IHC分析相当，并与死后组织的IHC分析相对应。我们发现RAMALT灵敏度（77.3%）在RT-QuIC和IHC分析之间高度相关。鼻刷试验敏感性较低（34%），尽管RAMALT和鼻刷试验敏感性均取决于PRNP基因型和obex评分确定的疾病进展。这些数据表明，RT-QuIC，像IHC分析，是一个相对敏感的检测慢性消耗病朊病毒在RAMALT活检标本，并与进一步的调查，有潜力的大规模和快速自动化测试的死前样本的慢性消耗病。
Chronic wasting disease (CWD), a transmissible spongiform encephalopathy of cervids, was first documented nearly 50 years ago in Colorado and Wyoming and has since been detected across North America and the Republic of Korea. The expansion of this disease makes the development of sensitive diagnostic assays and antemortem sampling techniques crucial for the mitigation of its spread; this is especially true in cases of relocation/reintroduction or prevalence studies of large or protected herds, where depopulation may be contraindicated. This study evaluated the sensitivity of the real-time quaking-induced conversion (RT-QuIC) assay of recto-anal mucosa-associated lymphoid tissue (RAMALT) biopsy specimens and nasal brushings collected antemortem. These findings were compared to results of immunohistochemistry (IHC) analysis of ante-and postmortem samples. RAMALT samples were collected from populations of farmed and free-ranging Rocky Mountain elk (Cervus elaphus nelsoni; n = 323), and nasal brush samples were collected from a subpopulation of these animals (n = 205). We hypothesized that the sensitivity of RT-QuIC would be comparable to that of IHC analysis of RAMALT and would correspond to that of IHC analysis of postmortem tissues. We found RAMALT sensitivity (77.3%) to be highly correlative between RT-QuIC and IHC analysis. Sensitivity was lower when testing nasal brushings (34%), though both RAMALT and nasal brush test sensitivities were dependent on both the PRNP genotype and disease progression determined by the obex score. These data suggest that RT-QuIC, like IHC analysis, is a relatively sensitive assay for detection of CWD prions in RAMALT biopsy specimens and, with further investigation, has potential for large-scale and rapid automated testing of antemortem samples for CWD.