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

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.

A novel strategy for molecular signature discovery based on independent component analysis.

Microarray analysis often leads to either too large or too small numbers of gene candidates to allow meaningful identification of functional signatures. We aimed at overcoming this hurdle by combining two algorithms: i. Independent Component Analysis to extract statistically-based potential signatures. ii. Gene Set Enrichment Analysis to produce a score of enrichment with statistical significance of each potential signature. We have applied this strategy to identify regulatory T cell (Treg) molecular signatures from two experiments in mice, with cross-validation. These signatures can detect the -1% Treg in whole spleen. These findings demonstrate the relevance of our approach as a signature discovery tool.