Myeloablation-associated deletion of ORF4 in a human coronavirus 229E infection.

Myeloablation-associated deletion of ORF4 in a human coronavirus 229E infection.
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DOI:
10.1038/s41525-017-0033-4
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发表时间:
2017
影响因子:
5.3
通讯作者:
Jerome KR
Jerome KR
中科院分区:
医学2区
文献类型:
--
作者:
Greninger AL;Pepper G;Shean RC;Cent A;Palileo I;Kuypers JM;Schiffer JT;Jerome KR

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我们描述了一种人类冠状病毒229 E的宏基因组下一代测序(mNGS),该冠状病毒来自一名患有AML和持续性上呼吸道症状的患者,该患者接受了造血细胞移植(HCT)。mNGS揭示了548个核苷酸的缺失,其包括几乎整个ORF 4基因,并且未检测到提示混合感染的次要等位基因变体。作为HCT前预处理方案的一部分,患者接受环磷酰胺清髓治疗和12戈伊全身照射。迭代测序和RT-PCR确认的4个呼吸道样本在4周的peritransplant期间显示,预处理菌株包含一个完整的ORF 4基因,而删除菌株出现后不久的条件和持续超过2.5周的时间。该序列代表了在人类RNA病毒中检测到的最大基因组缺失之一,并描述了与HCT骨髓消融相关的大规模病毒突变。
We describe metagenomic next-generation sequencing (mNGS) of a human coronavirus 229E from a patient with AML and persistent upper respiratory symptoms, who underwent hematopoietic cell transplantation (HCT). mNGS revealed a 548-nucleotide deletion, which comprised the near entirety of the ORF4 gene, and no minor allele variants were detected to suggest a mixed infection. As part of her pre-HCT conditioning regimen, the patient received myeloablative treatment with cyclophosphamide and 12 Gy total body irradiation. Iterative sequencing and RT-PCR confirmation of four respiratory samples over the 4-week peritransplant period revealed that the pre-conditioning strain contained an intact ORF4 gene, while the deletion strain appeared just after conditioning and persisted over a 2.5-week period. This sequence represents one of the largest genomic deletions detected in a human RNA virus and describes large-scale viral mutation associated with myeloablation for HCT.
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