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

Abstract

The ongoing COVID-19 pandemic has led to more than 159 million confirmed cases with over 3.3 million deaths worldwide, but it remains mystery why most infected individuals (∼98%) were asymptomatic or only experienced mild illness. The same mystery applies to the deadly 1918 H1N1 influenza pandemic, which has puzzled the field for a century. Here we discuss dual potential properties of the 1918 H1N1 pandemic viruses that led to the high fatality rate in the small portion of severe cases, while about 98% infected persons in the United States were self-limited with mild symptoms, or even asymptomatic. These variations now have been postulated to be impacted by polymorphisms of the sialic acid receptors in the general population. Since coronaviruses (CoVs) also recognize sialic acid receptors and cause severe acute respiratory syndrome epidemics and pandemics, similar principles of influenza virus evolution and pandemicity may also apply to CoVs. A potential common principle of pathogen/host co-evolution of influenza and CoVs under selection of host sialic acids in parallel with different epidemic and pandemic influenza and coronaviruses is discussed.

Keywords: 1918 H1N1 pandemic; Influenza and coronavirus; co-evolution; polymorphism; sialic acid receptor.

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 [17,18] were used. Recombinant H7N9 and 1918 H1N1 HAs were constructed and expressed as described previously [16]. 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 [13]. 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) [19]. (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.