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

Human mastadenovirus type 70: a novel, multiple recombinant species D mastadenovirus isolated from diarrhoeal faeces of a haematopoietic stem cell transplantation recipient
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DOI:
10.1099/vir.0.000196
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发表时间:
2015-09-01
影响因子:
3.8
通讯作者:
Heim, Albert
Heim, Albert
中科院分区:
医学3区
文献类型:
--
作者:
Hage, Elias;Liebert, Uwe Gerd;Heim, Albert

文献摘要

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从异基因造血干细胞移植(SCT)受者的粪便中分离的人肥大腺病毒D(HAdV-D)通过六邻体主要中和表位的环1和2的测序(“估算血清学”)发现是不可分型的。与HAdV-C相反,HAdV-D感染很少在SCT患者中观察到。因此,对该分离株的全基因组进行了测序和遗传学分析。此外,还使用型特异性抗血清进行了微量中和试验。获得了35.2kb长的完整基因组序列,GC含量为57%,并发现与HAdV-D27(96.25%同一性)远相关。插补血清学暗示了一种新的类型,其与HAdV-D37(环1)的核苷酸序列同一性仅为96.11%,与HAdV-D30和HAdV-D37(环2)的核苷酸序列同一性仅为95.76%。中和试验证实该临床分离株不被HAdV-D37或HAdV-D30特异性抗血清中和。五邻体碱基基因显示了一个新的序列,与HAdV-D38聚簇,但bootscan分析表明与HAdV-D 60发生了五邻体内重组事件。在早期基因区E3内检测到另一个重组事件,其具有来自HAdV-D58的12.2kDa和CR 1-α基因。此外,E4区来自HAdV-D13,但所有这些基因都从它们的祖先进化而来。相比之下,重组纤维基因与HAdV-D29几乎100%相同。总之,命名为HAdV-D 70 [P70 H70 F29]原型的这种新型HAdV的基因组学支持HAdV-D的遗传学中多次重组的重要性。
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-alpha 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.