Phylogenetic and recombination analysis of adenovirus isolates reveals discordance between serotype and phylogeny: Multiple sequence alignments

Background

Human adenovirus (HAdV) infections are caused by seven mastadenovirus species (A-G) and are the source for a variety of pathologies including gastrointestinal, respiratory, neurological, and ocular disease.  While HAdV-D is the most common cause of adenovirus ocular infections, human adenoviruses B and E have also been isolated from the eye. 

Results

In the course of classifying three new atypical ocular adenovirus samples, taken from the vitreous humor, we found that all three isolates were HAdV-B species, with isolate BP-AdV1 sorting with the B1 clade, and isolates BP-AdV2 and BP-AdV3 grouping into the B2 clade.  The three Bascom Palmer HAdV-B genomes were then combined with over 300 HAdV-B genome sequences, including 9 ocular HAdV-B genome sequences.  The whole genome phylogenetic analysis showed that 9 of the 11 ocular sequences grouped into the B1 clade, forming two clusters within B1.  Attempts to categorize the penton, hexon and fiber serotypes using phylogeny of the three Bascom Palmer samples were inconclusive due to incongruence between serotype and phylogeny in the dataset.  Recombination analysis using a subset of HAdV-B strains to generate a hybridization network detected recombination between non-human primate and human derived strains, recombination between one HAdV-B strain and the HAdV-E outgroup and limited recombination between the B1 and B2 clades. 

Conclusions

The discordance between serotype and phylogeny detected in this study suggests that the current penton/hexon/fiber-based classification mechanism does not accurately describe the natural history and phylogenetic relationships amongst adenoviruses. A new adenovirus strain classification strategy may be beneficial to the field.