Human adenovirus type 26 uses sialic acid - bearing glycans as a primary cell entry receptor

Baker, Alexander ORCID: https://orcid.org/0000-0001-8232-0531, Mundy, Rosie M., Davies, James A. ORCID: https://orcid.org/0000-0003-3569-4500, Rizkallah, Pierre and Parker, Alan L. ORCID: https://orcid.org/0000-0002-9302-1761 2019. Human adenovirus type 26 uses sialic acid - bearing glycans as a primary cell entry receptor. Science Advances 5 (9) , eaax3567. 10.1126/sciadv.aax3567

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Abstract

Adenoviruses are clinically important agents. They cause respiratory distress, gastroenteritis, and epidemic keratoconjunctivitis. As non-enveloped, double-stranded DNA viruses, they are easily manipulated, making them popular vectors for therapeutic applications, including vaccines. Species D adenovirus type 26 (HAdV-D26) is both a cause of EKC and other diseases and a promising vaccine vector. HAdV-D26–derived vaccines are under investigation as protective platforms against HIV, Zika, and respiratory syncytial virus infections and are in phase 3 clinical trials for Ebola. We recently demonstrated that HAdV-D26 does not use CD46 or Desmoglein-2 as entry receptors, while the putative interaction with coxsackie and adenovirus receptor is low affinity and unlikely to represent the primary cell receptor. Here, we establish sialic acid as a primary entry receptor used by HAdV-D26. We demonstrate that 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:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Publisher:	American Association for the Advancement of Science
ISSN:	2375-2548
Funders:	CRUK
Date of First Compliant Deposit:	23 August 2019
Date of Acceptance:	29 July 2019
Last Modified:	06 May 2023 10:25
URI:	https://orca.cardiff.ac.uk/id/eprint/125102

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