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造血干细胞移植后发生神经并发症患者脑脊液中的病毒组定义。

Virome definition in cerebrospinal fluid of patients with neurological complications after hematopoietic stem cell transplantation.

机构信息

Department of Cell and Molecular Biology, Karolinska Institutet, SE-171 77 Stockholm, Sweden.

Department of Clinical Science, Intervention and Technology, CLINTEC, Karolinska Institutet, S-141 86 Stockholm, Sweden.

出版信息

J Clin Virol. 2018 Nov;108:112-120. doi: 10.1016/j.jcv.2018.09.014. Epub 2018 Sep 30.

Abstract

BACKGROUND

Neurological complications (NC) in allogeneic hematopoietic stem cell transplant (HSCT) recipients lead to long-term sequelae and result in significant morbidity and mortality. Since risk factors for NC include viral infection or reactivation, virome inspection after HSCT might be helpful to the clinical management of patients after HSCT.

OBJECTIVES AND STUDY DESIGN

In this study we investigated whether any viruses are found in association with NC after HSCT. For this purpose, unbiased next generation sequencing (NGS) was used to characterize nucleic acid (NA) content in cerebrospinal fluid (CSF) taken at time of NC in 35 HSCT patients. Virome definition in CSF from non-transplanted subjects (controls) was also tested to define the commensal flora.

RESULTS AND CONCLUSIONS

A higher number of reads/contigs mapped to viruses in patients compared to the controls (7,626 vs 235). Besides bacteriophages, Torque teno virus (TTV) was also identified in both controls and patients. Interestingly, a significantly higher number of TTV-like sequences was detected in the patient samples (7,236 vs 9), showing similarities to distinct genotypes; 3/2,575, 2/1,692 and 2/2,969 contigs/reads mapped to TTV11, TTV13 and Torque teno midi virus, respectively. In conclusion, unbiased NGS demonstrated to be a suitable approach to characterize the virome in samples containing limiting amounts of NA. The higher TTV levels and genetic diversity found in CSF of subjects with NC after HSCT might suggest a possible association between TTV reactivation and the disorder. However, further studies are needed to evaluate the possible role of TTV on NC in HSCT patients.

摘要

背景

异基因造血干细胞移植(HSCT)受者的神经系统并发症(NC)会导致长期后遗症,并导致发病率和死亡率显著增加。由于 NC 的危险因素包括病毒感染或再激活,因此 HSCT 后进行病毒组检查可能有助于 HSCT 后患者的临床管理。

目的和研究设计

在这项研究中,我们调查了 HSCT 后与 NC 相关的病毒是否存在。为此,我们使用无偏下一代测序(NGS)来描述 35 名 HSCT 患者在出现 NC 时脑脊液(CSF)中的核酸(NA)含量。还测试了未移植受试者(对照)CSF 中的病毒组定义,以确定共生菌群。

结果和结论

与对照组相比,患者的测序读长/序列映射到病毒的数量更多(7626 对 235)。除了噬菌体,Torque teno 病毒(TTV)也在对照组和患者中均有发现。有趣的是,在患者样本中检测到的 TTV 样序列数量明显更高(7236 对 9),与不同基因型相似;3/2575、2/1692 和 2/2969 个序列/读长分别映射到 TTV11、TTV13 和 Torque teno midi 病毒。总之,无偏 NGS 被证明是一种合适的方法,可以用于对含有有限数量 NA 的样本中的病毒组进行特征描述。HSCT 后出现 NC 的患者 CSF 中 TTV 水平升高和遗传多样性增加,可能提示 TTV 再激活与该疾病之间存在关联。然而,需要进一步研究来评估 TTV 在 HSCT 患者 NC 中的可能作用。

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