Abstract

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.

Highlights

  • Mammalian cells are covered by a dense glycocalyx consisting of glycolipids, glycoproteins, and proteoglycans

  • An additional reason for human influenza susceptibility lies in the selective expression of ␣2–3-linked sialic acids (Sias) in the goblet cells that secrete mucins into the human upper airway lumen [17, 19]

  • All 11 samples of human trachea and lung samples showed intense Sambuccus nigra agglutinin (SNA) lectin staining of the cilia and their basal bodies at the luminal edge of the bronchiolar epithelial cells, indicating the presence of ␣2– 6-linked sialic acids

Read more

Summary

The abbreviations used are

Sialic acids; Neu5Ac, N-acetylneuraminic acid; Neu5Gc, N-glycolylneuraminic acid; ELISA, enzymelinked immunosorbent assay; CMAH, CMP-Neu5Ac hydroxylase; SNA, S. nigra agglutinin; MAH, M. amurensis hemagglutinin; TBS, Trisbuffered saline. Among the few documented functional genomic differences between humans and great apes, two affect Sia biology: an exon deletion in the CMAH gene explaining the lack of expression of the Sia N-glycolylneuraminic acid (Neu5Gc) in humans [25] and a point mutation eliminating the Sia binding property of human Siglec-L1 [26]. Given Ͻ100 known genes involved in biosynthesis, transfer, metabolism, and recognition of Sias, it is surprising to find so many differences in Sia biology between humans and great apes This prompted us to ask whether there are uniquely human features in the expression pattern of ␣2– 6-linked Sias. Such data are currently not available for any such well defined clade of related vertebrates

EXPERIMENTAL PROCEDURES
RESULTS
DISCUSSION
Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call