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人70型乳腺病毒:从一名造血干细胞移植受者腹泻粪便中分离出的一种新型多重重组的D种乳腺病毒

Human mastadenovirus type 70: a novel, multiple recombinant species D mastadenovirus isolated from diarrhoeal faeces of a haematopoietic stem cell transplantation recipient.

作者信息

Hage Elias, Gerd Liebert Uwe, Bergs Sandra, Ganzenmueller Tina, Heim Albert

机构信息

Institut für Virologie, Adenovirus Konsiliarlabor, Medizinische Hochschule Hannover, Hannover, Germany.

Deutsches Zentrum Infektionsforschung, Hannover and Braunschweig, Germany.

出版信息

J Gen Virol. 2015 Sep;96(9):2734-2742. doi: 10.1099/vir.0.000196. Epub 2015 May 22.

Abstract

A human mastadenovirus D (HAdV-D) isolated from diarrhoeal faeces of an allogeneic haematopoietic stem cell transplant (SCT) recipient was found to be non-typable by sequencing of loops 1 and 2 of the hexon main neutralization epitope ('imputed serology'). In contrast to HAdV-C, HAdV-D infections are rarely observed in SCT patients. Therefore, the whole genome of this isolate was sequenced and phylogenetically analysed. In addition, microneutralization testing with type-specific antisera was performed. A complete genomic sequence of 35.2 kb in length with a GC content of 57  % was obtained and found to be distantly related to HAdV-D27 (96.25 % identity). Imputed serology implicated a new type with a nucleotide sequence identity of only 96.11 % to HAdV-D37 (loop 1) and 95.76 % to HAdV-D30 and HAdV-D37 (loop 2). Microneutralization testing confirmed that this clinical isolate was not neutralized by HAdV-D37- or HAdV-D30-specific antisera. The penton base gene showed a novel sequence, which clustered with HAdV-D38, but bootscan analysis indicated an intra-penton recombination event with HAdV-D60. Another recombination event was detected within the early gene region E3 with the 12.2 kDa and CR1-α genes derived from HAdV-D58. Moreover, the E4 region was derived from HAdV-D13, but all these genes had evolved significantly from their ancestors. By contrast, the recombinant fibre gene was almost 100 % identical to HAdV-D29. In conclusion, the genomics of this novel HAdV, designated the HAdV-D70 [P70H70F29] prototype, supported the significance of multiple recombinations in the phylogeny of HAdV-D.

摘要

从一名异基因造血干细胞移植(SCT)受者的腹泻粪便中分离出的一株人腺病毒D(HAdV-D),通过对六邻体主要中和表位的环1和环2进行测序(“推测血清学”)发现其无法分型。与HAdV-C不同,SCT患者中很少观察到HAdV-D感染。因此,对该分离株的全基因组进行了测序和系统发育分析。此外,还进行了型特异性抗血清的微量中和试验。获得了一个长度为35.2 kb、GC含量为57%的完整基因组序列,发现其与HAdV-D27的亲缘关系较远(同一性为96.25%)。推测血清学表明这是一种新型,其核苷酸序列与HAdV-D37(环1)的同一性仅为96.11%,与HAdV-D30和HAdV-D37(环2)的同一性为95.76%。微量中和试验证实,该临床分离株不能被HAdV-D37或HAdV-D30特异性抗血清中和。五邻体基底基因显示出一个新序列,与HAdV-D38聚集在一起,但引导扫描分析表明与HAdV-D60发生了一次五邻体内部重组事件。在早期基因区域E3内检测到另一次重组事件,其中的12.2 kDa和CR1-α基因来自HAdV-D58。此外,E4区域来自HAdV-D13,但所有这些基因与其祖先相比都有了显著进化。相比之下,重组纤维基因与HAdV-D29几乎100%相同。总之,这种新型HAdV的基因组学,命名为HAdV-D70 [P70H70F29]原型,支持了多次重组在HAdV-D系统发育中的重要性。

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