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

Sci Adv. 2019 Sep 4;5(9):eaax3567. doi: 10.1126/sciadv.aax3567. eCollection 2019 Sep.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenovirus Vaccines / metabolism
  • Adenoviruses, Human / chemistry*
  • Adenoviruses, Human / metabolism
  • Crystallography, X-Ray
  • HEK293 Cells
  • Humans
  • Keratoconjunctivitis / epidemiology
  • Keratoconjunctivitis / metabolism
  • Keratoconjunctivitis / pathology
  • N-Acetylneuraminic Acid / chemistry*
  • N-Acetylneuraminic Acid / metabolism
  • Receptors, Virus / chemistry*
  • Receptors, Virus / metabolism
  • Viral Proteins / chemistry*
  • Viral Proteins / metabolism


  • Adenovirus Vaccines
  • Receptors, Virus
  • Viral Proteins
  • adenovirus receptor
  • N-Acetylneuraminic Acid