Hage Elias, Gerd Liebert Uwe, Bergs Sandra, Ganzenmueller Tina, Heim Albert
Institut für Virologie, Adenovirus Konsiliarlabor, Medizinische Hochschule Hannover, Hannover, Germany.
Deutsches Zentrum Infektionsforschung, Hannover and Braunschweig, Germany.
J Gen Virol. 2015 Sep;96(9):2734-2742. doi: 10.1099/vir.0.000196. Epub 2015 May 22.
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.
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。