AI Summary
Human adenoviruses (HAdV) are common viruses that usually cause mild infections. HAdV-D, a specific type, can cause gastrointestinal and eye infections. This study investigates the mechanism of cell infection by HAdV-D and highlights the role of sialic acid (SA) engagement. The researchers provide crystal structures of HAdV-D proteins and demonstrate that removing SA from cell surfaces reduces infectivity. Understanding these interactions can help develop antiviral treatments and therapeutic vectors.
Human adenoviruses (HAdV) are widespread pathogens causing usually mild infections. The Species D (HAdV-D) cause gastrointestinal tract infections and epidemic keratoconjunctivitis (EKC). Despite being significant pathogens, knowledge around HAdV-D mechanism of cell infection is lacking. Sialic acid (SA) usage has been proposed as a cell infection mechanism for EKC causing HAdV-D. Here we highlight an important role for SA engagement by many HAdV-D. We provide apo state crystal structures of 7 previously undetermined HAdV-D fiber-knob proteins, and structures of HAdV-D25, D29, D30 and D53 fiber-knob proteins in complex with SA. Biologically, we demonstrate that removal of cell surface SA reduced infectivity of HAdV-C5 vectors pseudotyped with HAdV-D fiber-knob proteins, whilst engagement of the classical HAdV receptor CAR was variable. Our data indicates variable usage of SA and CAR across HAdV-D. Better defining these interactions will enable improved development of antivirals and engineering of the viruses into refined therapeutic vectors.
Human adenoviruses (HAdV) are classified phylogenetically into seven species, A-G, based classically on testing for neutralizing activity by serological analysis1, (2019).” href=”https://www.nature.com/articles/s44298-023-00001-5#ref-CR2″ id=”ref-link-section-d149181795e549″>2. They are highly diverse, and have become of great