Abstract
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 in vivo studies investigating cross-protection against IBH.
Highlights
IntroductionFowl adenoviruses (FAdVs), belonging to the genus Aviadenovirus (family Adenoviridae), are mainly isolated from chickens, but sporadically from other avian hosts [1]
Fowl adenoviruses (FAdVs), belonging to the genus Aviadenovirus, are mainly isolated from chickens, but sporadically from other avian hosts [1]
These include examples of allegedly less common interspecies and intergenus recombination events, which were described for a novel, non-chicken AdV mosaïc of sequences with different aviadenovirus origin [63]
Summary
Fowl adenoviruses (FAdVs), belonging to the genus Aviadenovirus (family Adenoviridae), are mainly isolated from chickens, but sporadically from other avian hosts [1]. The wealth of hexon data has critically contributed to the recognition of specific types for distinct clinical pictures [6,7], systematic intergenomic comparisons of FAdVs outside this approach are lagging far behind the state-of-art in mammalian, human adenoviruses (HAdVs) of the genus Mastadenovirus. For genomes of contemporary field strains, there had so far only been singular contributions to public databases. This situation has changed for FAdV-4 (FAdV-C), with the sudden appearance of hepatitis-hydropericardium syndrome (HHS) in China, leading to an extensive supply of the relevant sequences [10,11,12]
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