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

Baker, Alexander, Mundy, Rosie M., Davies, James A., Rizkallah, Pierre and Parker, Alan L. 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: 30 Nov 2019 06:41
URI: http://orca-mwe.cf.ac.uk/id/eprint/125102

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