Adenovirus serotype 26 utilises sialic acid bearing glycans as a primary cell entry receptor

Baker, Alexander T. ORCID: https://orcid.org/0000-0001-8232-0531, Mundy, Rosie, Davies, James ORCID: https://orcid.org/0000-0003-3569-4500, Rizkillah, Pierre T. and Parker, Alan L. ORCID: https://orcid.org/0000-0002-9302-1761 2019. Adenovirus serotype 26 utilises sialic acid bearing glycans as a primary cell entry receptor. [Online]. bioRxiv. Available at: https://doi.org/10.1101/580076

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Abstract

Adenoviruses are clinically important agents. They cause respiratory distress, gastroenteritis, and epidemic keratoconjunctivitis (EKC). As non-enveloped, double stranded DNA viruses, they are easily manipulated, making them popular vectors for therapeutic applications, including vaccines. Species D adenovirus serotype 26 (HAdV-D26) is both a cause of EKC and other disease, and a promising vaccine vector. HAdV-D26 derived vaccines are under investigation as protective platforms against HIV, Zika, RSV infections and are in Phase-III clinical trials for Ebola. We recently demonstrated that HAdV-D26 does not utilise CD46 or desmoglein 2 as entry receptors, whilst the putative interaction with Coxsackie and Adenovirus Receptor (CAR) is low affinity and unlikely to represent the primary cell receptor. Here, we definitively establish sialic acid as the primary entry receptor utilised by HAdV-D26. We demonstrate removal of cell surface sialic acid inhibits HAdV-D26 infection and provide a high-resolution crystal structure of HAdV-D26 fiber-knob in complex with sialic acid.

Item Type:	Website Content
Date Type:	Published Online
Status:	Submitted
Schools:	Medicine
Publisher:	bioRxiv
Date of Acceptance:	21 June 2019
Last Modified:	16 Nov 2024 10:15
URI:	https://orca.cardiff.ac.uk/id/eprint/124955

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