Christian Doppler Laboratory for Innovative Poultry Vaccines, University of Veterinary Medicine, 1210 Vienna, Austria.
Division of Bioinformatics, Research Center for Zoonosis Control, Hokkaido University, Sapporo 001-0020, Japan.
Viruses. 2019 Nov 26;11(12):1094. doi: 10.3390/v11121094.
After analyzing 27 new genomes from fowl adenovirus (FAdV) field isolates and so-far unsequenced prototypes, we report the first evidence for recombination in FAdVs. Recombination was confined to species FAdV-D and FAdV-E, accommodating the largest number of, and the intraspecies-wise most differentiated, types. The majority of detected events occurred in FAdV-E, involving segments with parental origin of all constitutive types. Together with the diversity of breakpoints, this suggests widespread recombination in this species. With possible constraints through species-specific genes and diversification patterns, the recombinogenic potential of FAdVs attains particular interest for inclusion body hepatitis (IBH), an important disease in chickens, caused by types from the recombination-prone species. Autonomously evolving, recombinant segments were associated with major sites under positive selection, among them the capsid protein hexon and fiber genes, the right-terminal ORFs 19, 25, and the ORF20/20A family. The observed mosaicism in genes indicated as targets of adaptive pressures points toward an immune evasion strategy. Intertypic hexon/fiber-recombinants demonstrated hybrid neutralization profiles, retrospectively explaining reported controversies on reference strains B3-A, T8-A, and X11-A. Furthermore, cross-neutralization supported sequence-based evidence for interdomain recombination in fiber and contributed to a tentatively new type. Overall, our findings challenge the purported uniformity of types responsible for IBH, urging more complete identification strategies for FAdVs. Finally, important consequences arise for studies investigating cross-protection against IBH.
在分析了 27 株来自禽腺病毒（FAdV）田间分离株和迄今尚未测序的原型株的新基因组后，我们首次报道了 FAdV 中存在重组的证据。重组仅限于 FAdV-D 和 FAdV-E 种，容纳了最多的、种内分化最大的类型。检测到的大多数事件发生在 FAdV-E 中，涉及所有组成型的亲本来源的片段。与断点的多样性一起，这表明该物种中广泛存在重组。由于种特异性基因和多样化模式的可能限制，FAdV 的重组潜能对于包涵体肝炎（IBH）尤其感兴趣，IBH 是一种由易发生重组的种引起的鸡的重要疾病。自主进化的重组片段与主要的正选择位点相关，其中包括衣壳蛋白 hexon 和纤维基因、右末端 ORF19、25 和 ORF20/20A 家族。观察到的作为适应压力目标的基因镶嵌现象表明存在免疫逃避策略。不同类型的 hexon/fiber-重组体表现出混合中和谱，回顾性地解释了关于参考株 B3-A、T8-A 和 X11-A 的报道争议。此外，交叉中和支持纤维中域间重组的序列证据，并促成了一个暂定的新类型。总的来说，我们的发现挑战了 IBH 相关类型的一致性观点，迫切需要更完整的 FAdV 鉴定策略。最后，对于研究 IBH 交叉保护的研究产生了重要影响。
