Broad sialic acid usage amongst species D human adenovirus

Mundy, Rosie M., Baker, Alexander T. ORCID: https://orcid.org/0000-0001-8232-0531, Bates, Emily A., Cunliffe, Tabitha G., Teijeira Crespo, Alicia, Moses, Elise, Rizkallah, Pierre J. ORCID: https://orcid.org/0000-0002-9290-0369 and Parker, Alan L. ORCID: https://orcid.org/0000-0002-9302-1761 2023. Broad sialic acid usage amongst species D human adenovirus. npj Viruses 1 , 1. 10.1038/s44298-023-00001-5

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Abstract

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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
ISSN:	2948-1767
Funders:	MRC, Cancer Research UK, Wellcome Trust
Date of First Compliant Deposit:	26 September 2023
Date of Acceptance:	27 July 2023
Last Modified:	30 Oct 2023 18:02
URI:	https://orca.cardiff.ac.uk/id/eprint/162768

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