Genomic Mosaicism in Fowl Adenovirus 3 Strains

Adenoviral inclusion body hepatitis in chicken has been, in part, associated with serotypes of fowl adenovirus D. We determined the genome of 44 FAdV-D isolates collected from parts of the world, including 43 FAdV-2/-11 and a rare FAdV-3. This study focused on the sole FAdV-3 isolate, showing evidence of a mosaic structure of the viral genome. These findings highlight the need for full-genome analysis of rarely isolated virus variants to better reconstruct their evolution and epidemiology. Fowl adenovirus D is the main cause of inclusion body hepatitis in chickens. Whole genome sequencing was carried out to enrich the genomic sequence database using field isolates of FAdV-D. Out of 44 newly determined genomes, 43 were classified into FAdV-2/-11 and 2 into FAdV-3; no FAdV-9 was identified. Whole-genome based phylogeny showed that FAdV-3 was more distantly related to FAdV 9 and FAdV-2/-11 than FAdV-9 and FAdV-2/-11 to each other. Whole-genome sequence homology analysis revealed that the full-length FAdV-3 genome harbored a similar to 12 kbp fragment of the genome that shared moderate sequence homology with representative strains of other FAdV-D serotypes but high relatedness with only the FAdV-3 strain whose full-genome is available in GenBank. A closer look onto the fiber and the penton genes of our FAdV-3 isolate identified putative recombination events; both the fiber and the penton coding genes shared fragments originating from FAdV-9. Of interest, ORF19 displayed a close relationship with the homologous genomic region of some FAdV-E strains (amino acid sequence homology, up to 82%). Thus, although FAdV-3 is classified into FAdV-D, the genomic structure of FAdV-3 appears to result from multiple heterotypic and heterologous recombination events. This study highlights the unique origin of FAdV-3.