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Influenza Infections

Intra-species sialic acid polymorphism in humans: a common niche for influenza and coronavirus pandemics?

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Pages 1191-1199 | Received 30 Mar 2021, Accepted 18 May 2021, Published online: 14 Jun 2021

Figures & data

Figure 1. Binding assays of H7N9 and 1918 H1N1 HAs with saliva samples from a panel of health adults. Saliva samples from healthy employees in the Cincinnati Children’s Hospital Medical Center collected for studies of norovirus and rotavirus binding profiles of host histo blood group antigens in our previous studies [Citation17,Citation18] were used. Recombinant H7N9 and 1918 H1N1 HAs were constructed and expressed as described previously [Citation16]. The 95 tested saliva sample donors were sorted based on the OD binding signals of H7N9 HA (top panel).

Figure 1. Binding assays of H7N9 and 1918 H1N1 HAs with saliva samples from a panel of health adults. Saliva samples from healthy employees in the Cincinnati Children’s Hospital Medical Center collected for studies of norovirus and rotavirus binding profiles of host histo blood group antigens in our previous studies [Citation17,Citation18] were used. Recombinant H7N9 and 1918 H1N1 HAs were constructed and expressed as described previously [Citation16]. The 95 tested saliva sample donors were sorted based on the OD binding signals of H7N9 HA (top panel).

Figure 2. Saliva binding profiles of H7N9 HA in association with the sialic acid types of saliva donors. The binding signals of sialic Lewis a (SLe a), sialic Lewis x (SLe x), Lewis b (Le b) and Lewis y (Le y) in the saliva samples were performed ELISA using commercial monoclonal antibodies described previously [Citation13]. The 95 tested saliva sample donors were sorted based on the OD binding signals of H7N9 HA (top panel).

Figure 2. Saliva binding profiles of H7N9 HA in association with the sialic acid types of saliva donors. The binding signals of sialic Lewis a (SLe a), sialic Lewis x (SLe x), Lewis b (Le b) and Lewis y (Le y) in the saliva samples were performed ELISA using commercial monoclonal antibodies described previously [Citation13]. The 95 tested saliva sample donors were sorted based on the OD binding signals of H7N9 HA (top panel).

Figure 3. Synthesis of the ABH and Lewis histo-blood group antigens and deduced blocking or masking of synthesis of 2,3-sialic acid antigens by preoccupied 1,2-linked fucose by the H fucose-transferase encoded by the FUT 2 gene in humans. (A) Biosynthesis of type 1 based HBGAs. Synthesis proceeds by stepwise addition of monosaccharide units from a precursor disaccharide present at the terminus of glycan chains from either O-linked or N-linked glycans of glycoproteins, or from glycolipids (R) [Citation19]. (B) Deduced blocking or masking of synthesis of the 2,3-sialic acid antigens by preoccupied 1,2-linked fucose synthesized by the H fucose-transferase encoded by the FUT 2 gene in humans following a study of H7N9-infected patients involved in an outbreak in China in season 2016/17. Around 80% of the general populations are secretor positive and the expression of the 2,3-linked sialic acids are blocked or masked by the preoccupied 1,2-linked fucose, suggesting that secretors may be naturally resistant to H7N9 IAVs because they mainly express the 2, 6-linked sialic acids in the upper respiratory tracts and may not express or express low amounts of 2,3-linked sialic acids in their lower respiratory tracts. The 20% non-secretors may also express 2,6-linked sialic acids in the upper respiratory tracts but mainly express the 2,3-linked sialic acids in the lower respiratory tracts.

Figure 3. Synthesis of the ABH and Lewis histo-blood group antigens and deduced blocking or masking of synthesis of 2,3-sialic acid antigens by preoccupied 1,2-linked fucose by the H fucose-transferase encoded by the FUT 2 gene in humans. (A) Biosynthesis of type 1 based HBGAs. Synthesis proceeds by stepwise addition of monosaccharide units from a precursor disaccharide present at the terminus of glycan chains from either O-linked or N-linked glycans of glycoproteins, or from glycolipids (R) [Citation19]. (B) Deduced blocking or masking of synthesis of the 2,3-sialic acid antigens by preoccupied 1,2-linked fucose synthesized by the H fucose-transferase encoded by the FUT 2 gene in humans following a study of H7N9-infected patients involved in an outbreak in China in season 2016/17. Around 80% of the general populations are secretor positive and the expression of the 2,3-linked sialic acids are blocked or masked by the preoccupied 1,2-linked fucose, suggesting that secretors may be naturally resistant to H7N9 IAVs because they mainly express the 2, 6-linked sialic acids in the upper respiratory tracts and may not express or express low amounts of 2,3-linked sialic acids in their lower respiratory tracts. The 20% non-secretors may also express 2,6-linked sialic acids in the upper respiratory tracts but mainly express the 2,3-linked sialic acids in the lower respiratory tracts.

Table 1. Deduced sialic acids and their glycan linkages as receptors for selected human and zoonotic IAVs and CoVs.