Powassan Virus Neuropathology and Genomic Diversity in Patients With Fatal Encephalitis.
Powassan Virus Neuropathology and Genomic Diversity in Patients With Fatal Encephalitis.
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DOI：
10.1093/ofid/ofaa392
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发表时间：
2020-10
影响因子：
4.2
通讯作者：
Piantadosi A
中科院分区：
文献类型：
--
作者：
Normandin E;Solomon IH;Zamirpour S;Lemieux J;Freije CA;Mukerji SS;Tomkins-Tinch C;Park D;Sabeti PC;Piantadosi A
Powassan病毒（POWV）是严重脑炎的一种新兴病因;由于诊断和病毒RNA回收方面的挑战，对人类致病性知之甚少。我们提出3例致命性脑炎由于POWV谱系II（鹿蜱病毒）。 我们获得了27个独特的样本，包括来自脑活检和尸检的样本，并使用宏基因组测序，定量逆转录酶聚合酶链反应和新开发的基于CRISPR的诊断分析，对人类受试者之间和内部的POWV区室化和基因组学进行了首次详细表征。 在所有3例患者中，影像学和组织病理学结果均以严重的小脑受累为特征。所有患者均通过宏基因组测序初步诊断为POWV，其中2例血清学临床检测阴性。我们在13个临床样本中检测到POWV RNA;小脑中的水平最高，并且很少涉及外周组织。我们从8个样本中组装了完整的POWV基因组，提供了关于感染人类的POWV谱系II（鹿蜱病毒）菌株的独特信息。 我们证明了检测POWV感染的分子检测方法的实用性，包括在血清阴性患者中，并提名可能与人类感染和神经致病性相关的病毒基因组特征。小脑被确定为一个关键的目标POWV在致命的感染，放射学和组织病理学的结果以及分子检测。在三名致命性脑炎患者中，通过宏基因组测序诊断出Powassan病毒。27个独特的样本的成像，组织病理学和分子检测显示出深刻的小脑参与，很少周围。Powassan病毒基因组测序提供了对感染人类的菌株的深入了解。
Powassan virus (POWV) is an emerging cause of severe encephalitis; very little is known about human pathogenicity due to challenges in diagnosis and viral RNA recovery. We present 3 patients with fatal encephalitis due to POWV lineage II (deer tick virus). We obtained 27 unique samples, including from brain biopsy and autopsy, and used metagenomic sequencing, quantitative reverse transcriptase polymerase chain reaction, and a newly developed CRISPR-based diagnostic assay to perform the first detailed characterization of POWV compartmentalization and genomics between and within human subjects. In all 3 patients, imaging and histopathology findings were notable for profound cerebellar involvement. All patients were initially diagnosed with POWV by metagenomic sequencing, and 2 of the 3 had negative clinical testing by serology. We detected POWV RNA in 13 clinical samples; levels were highest in the cerebellum, and there was very little involvement of peripheral tissue. We assembled complete POWV genomes from 8 samples, providing unique information about the strains of POWV lineage II (deer tick virus) that infect humans. We demonstrate the utility of molecular assays for detecting POWV infection, including in seronegative patients, and nominate viral genomic features that may relate to human infection and neuropathogenicity. The cerebellum was identified as a key target POWV in fatal infection, by radiological and histopathological findings as well as molecular testing. In three patients with fatal encephalitis, Powassan virus was diagnosed by metagenomic sequencing. Imaging, histopathology, and molecular testing of 27 unique samples showed profound cerebellar involvement, and little peripherally. Powassan virus genome sequencing offered insight into strains that infect humans.
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影响因子：
10.7
作者：
Minh BQ;Nguyen MA;von Haeseler A
通讯作者：
von Haeseler A
影响因子：
15.9
作者：
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通讯作者：
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影响因子：
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作者：
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作者：
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通讯作者：
Sabeti, Pardis C.