Human-specific Regulation of α2–6-linked Sialic Acids

Abstract

Many microbial pathogens and toxins recognize animal cells via cell surface sialic acids (Sias) that are ␣2-3-or ␣2-8-linked to the underlying glycan chain. Human influenza A/B viruses are unusual in preferring ␣2-6-linked Sias, undergoing a switch from ␣2-3 linkage preference during adaptation from animals to humans. This correlates with the expression of ␣2-6-linked Sias on ciliated human airway epithelial target cells and of ␣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 ␣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 ␣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 ␣2-6-linked Sias, only human erythrocytes have markedly up-regulated expression. These cell type-specific changes in ␣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.

Large-scale sequencing of the CD33-related Siglec gene cluster in five mammalian species reveals rapid evolution by multiple mechanisms

“…Thus, the process of speciation itself may be solely responsible for the observed between-species differences of CD33rSiglecs. The observed betweenspecies differences reported here are also concordant with our recent finding that humans show distinct patterns of terminal sialylation differing in multiple tissues from those of chimpanzee, bonobo, gorilla, or orangutan (37).…”

Alteraciones morfológicas en pulmón por la influenza A H1N1/v09 en autopsias, Colombia, 2009

“…Micrografía electrónica de tejido pulmonar con infección por virus de influenza A H1N1/v09. endosoma en la célula huésped (28,29); asimismo, algunos estudios han señalado que las células que presentan los receptores de unión al virus están localizadas predominantemente en el epitelio bronquiolar, y su cantidad es menor en el epitelio alveolar (30). Taubenberger, et al (2010), reportaron marcaciones para el antígeno en el epitelio pseudoestratificado del árbol traquebronquial y en el epitelio bronquiolar, en casos de autopsia (12).…”

Molecular Phylogeny and Functional Genomics of β-Galactoside α2,6-Sialyltransferases That Explain Ubiquitous Expression of st6gal1 Gene in Amniotes

“…This rapid complication of the genetic/epigenetic regulation of expression of the st6gal1 gene has led to a diversification of the tissue distribution and also of function in higher vertebrates. Indeed, phenotypic variation in ␣2,6-sialylation of N-glycosylproteins has been observed in various animals and in particular in mammals despite genetic conservation of their translated gene sequences (24). The patterns of tissue ␣2,6-sialylation of N-glycosylproteins differ widely among mammals, even among closely related taxa, such as mice and humans, which diverged only 96 MYA (68, 96 -98), or great apes and humans, which diverged 13-14 MYA (28,96).…”

“…Integrin-mediated adhesion is based on protein interactions, and binding can be significantly modulated by sia6LacNAc structures on ␤1-integrin in vivo and in vitro in cancer cells, leading to enhanced cell motility and invasiveness (21)(22)(23). ST6Gal I plays a role in inflammation (24,25), and in mammals, transient up-regulation occurs during acute phase reaction when the organism experiences trauma or infection (26,27). Finally, in contrast to avian and other mammalian influenza viruses, human influenza virus A and B prefer the ␣2,6-linked sialic acid found in abundance in human upper airways over the ␣2-3-linked sialic acid (28 -30).…”