Human-specific regulation of alpha 2-6-linked sialic acids

Bibliographic Collection: 
CARTA-Inspired Publication, APE
Publication Type: Journal Article
Authors: Gagneux, P.; Cheriyan, M.; Hurtado-Ziola, N.; van der Linden, E. C.; Anderson, D.; McClure, H.; Ajit Varki; Nissi M Varki
Year of Publication: 2003
Journal: J Biol Chem
Volume: 278
Edition: 2003/09/23
Number: 48
Pagination: 48245-50
Date Published: Nov 28
Type of Article: Research Support, Non-U.S. Gov'tResearch Support, U.S. Gov't, P.H.S.
Publication Language: eng
ISBN Number: 0021-9258 (Print)0021-92
Accession Number: 14500706 PMID
Keywords: *Cell Adhesion Molecules, Animals, Antigens, B-Lymphocyte/biosynthesis, Biotinylation, CD/biosynthesis, CD22, Cells, Cultured, Differentiation, Edetic Acid/pharmacology, Enzyme-Linked Immunosorbent Assay, Epithelial Cells/metabolism, F

Many microbial pathogens and toxins recognize animal cells via cell surface sialic acids (Sias) that are alpha 2-3- or alpha 2-8-linked to the underlying glycan chain. Human influenza A/B viruses are unusual in preferring alpha 2-6-linked Sias, undergoing a switch from alpha 2-3 linkage preference during adaptation from animals to humans. This correlates with the expression of alpha 2-6-linked Sias on ciliated human airway epithelial target cells and of alpha 2-3-linked Sias on secreted soluble airway mucins, which are unable to inhibit virus binding. Given several known differences in Sia biology between humans and apes, we asked whether this pattern of airway epithelial Sia linkages is also human-specific. Indeed, we show that since the last common ancestor with apes, humans underwent a concerted bidirectional switch in alpha 2-6-linked Sia expression between airway epithelial cell surfaces and secreted mucins. This can explain why the chimpanzee appears relatively resistant to experimental infection with human Influenza viruses. Other tissues showed additional examples of human-specific increases or decreases in alpha 2-6-linked Sia expression and only one example of a change specific to certain great apes. Furthermore, while human and great ape leukocytes both express alpha 2-6-linked Sias, only human erythrocytes have markedly up-regulated expression. These cell type-specific changes in alpha 2-6-Sia expression during human evolution represent another example of a human-specific change in Sia biology. Because the data set involves multiple great apes, we can also conclude that Sia linkage expression patterns can be conserved during millions of years of evolution within some vertebrate taxa while undergoing sudden major changes in other closely related ones.


J Biol Chem. 2003 Nov 28;278(48):48245-50. Epub 2003 Sep 18

Alternate Journal: The Journal of biological chemistry
Author Address:

Glycobiology Research and Training Center, Department of Medicine, University of California San Diego, La Jolla, California 92093-0687, USA.