Cryo-EM structure of enteric adenovirus HAdV-F41 highlights structural divergence among human adenoviruses

Enteric adenoviruses are one of the main causes of viral gastroenteritis in the world. To carry out a successful infection, the virions must withstand the harsh conditions found in the gut. This requirement suggests that capsid stability must be different from that of other adenoviruses. We have determined the structure of a human enteric adenovirus, HAdV-F41, at 4.0 [A] resolution by single particle averaging cryo-electron microscopy, and compared it with that of other adenoviruses with respiratory (HAdV-C5) and ocular (HAdV-D26) tropisms. While the overall structures of hexon, penton base and internal minor coat proteins IIIa and VIII are conserved, we observe partially ordered elements reinforcing the vertex region, which suggests their role in enhancing the physicochemical capsid stability of HAdV-F41. Unexpectedly, we find an organization of the external minor coat protein IX different from all previously characterized human and non-human mastadenoviruses. Knowledge of the structure of enteric adenoviruses can provide a starting point for the design of vectors suitable for oral delivery or intestinal targeting.