Molecular evolution of human adenovirus type 16 through multiple recombination events

Human mastadenoviruses (HAdVs) are non-enveloped, double-stranded DNA viruses that are comprised of more than 85 types classified within seven species (A-G) based on genomics. All HAdV prototypes and many newly defined type genomes have been completely sequenced and are available. Computational analyses of the prototypes and newly emergent HAdV strains provide insights into the evolutionary history and molecular adaptation of HAdV. Most types of HAdV-B are important pathogens causing severe respiratory infections or urinary tract infections and are well characterized. However, HAdV-16 of the B1 subspecies has rarely been reported and its genome is poorly characterized. In this study, bioinformatics analysis, based on genome sequences obtained in GenBank, suggested that HAdV-16, a prototype HAdV-B species, evolved from multiple intertypic recombination events. HAdV-16 genome contains the hexon loop 1 to loop 2 region from HAdV-E4, the partial hexon conserved region 4 (C4) from the subspecies HAdV-B2, genome region 30,897-33,384 containing the fiber gene from SAdV-35, and other genomic parts from the subspecies HAdV-B1. Moreover, analysis of sequence similarity with HAdV-E4 LI, LII, and SAdV-36 strains demonstrated the recombination events happened rather early. Further, amino acid sequence alignment indicated that the amino acid variations occurred in hypervariable regions (HVRs). Especially, the major difference in HVR7, which contains the critical neutralization epitope of HAdV-E4, between HAdV-16 and HAdV-E4 might explain the low level of cross-neutralization between these strains. Our findings promote better understanding on HAdV evolution, predicting newly emergent HAdV strains, and developing novel HAdV vectors.