Comparative distribution of human and avian type sialic acid influenza receptors in the pig

Abstract

BackgroundA major determinant of influenza infection is the presence of virus receptors on susceptible host cells to which the viral haemagglutinin is able to bind. Avian viruses preferentially bind to sialic acid α2,3-galactose (SAα2,3-Gal) linked receptors, whereas human strains bind to sialic acid α2,6-galactose (SAα2,6-Gal) linked receptors. To date, there has been no detailed account published on the distribution of SA receptors in the pig, a model host that is susceptible to avian and human influenza subtypes, thus with potential for virus reassortment. We examined the relative expression and spatial distribution of SAα2,3-GalG(1-3)GalNAc and SAα2,6-Gal receptors in the major organs from normal post-weaned pigs by binding with lectins Maackia amurensis agglutinins (MAA II) and Sambucus nigra agglutinin (SNA) respectively.ResultsBoth SAα2,3-Gal and SAα2,6-Gal receptors were extensively detected in the major porcine organs examined (trachea, lung, liver, kidney, spleen, heart, skeletal muscle, cerebrum, small intestine and colon). Furthermore, distribution of both SA receptors in the pig respiratory tract closely resembled the published data of the human tract. Similar expression patterns of SA receptors between pig and human in other major organs were found, with exception of the intestinal tract. Unlike the limited reports on the scarcity of influenza receptors in human intestines, we found increasing presence of SAα2,3-Gal and SAα2,6-Gal receptors from duodenum to colon in the pig.ConclusionsThe extensive presence of SAα2,3-Gal and SAα2,6-Gal receptors in the major organs examined suggests that each major organ may be permissive to influenza virus entry or infection. The high similarity of SA expression patterns between pig and human, in particular in the respiratory tract, suggests that pigs are not more likely to be potential hosts for virus reassortment than humans. Our finding of relative abundance of SA receptors in the pig intestines highlights a need for clarification on the presence of SA receptors in the human intestinal tract.

Positive selection for gains of N-linked glycosylation sites in hemagglutinin during evolution of H3N2 human influenza A virus

“…It should be noted that the number of N-linked glycosylation sites has increased only in the influenza A viruses circulating in human. In particular, the number stayed constant in influenza A viruses circulating in swine, which apparently expresses similar distributions of the receptors with sialic acid α2,3-galactose and α2,6-galactose linkages in organs (Nelli et al, 2010;Sriwilaijaroen et al, 2011), but weaker immune responses against influenza A viruses (Nerome et al, 1995) compared with human. These observations suggest that the target of positive selection was not the receptor binding but the shielding of antigenic sites by the gains of N-linked glycosylation sites in human H3N2 virus.…”

A Sialylated Glycan Microarray Reveals Novel Interactions of Modified Sialic Acids with Proteins and Viruses

“…Much of our understanding about the occurrence of sialic acids in cells and tissues has come from chemical analysis or histochemical staining of samples with the sialic acid-specific lectins SNA and MAL-I (40,41). Detailed specificity studies on SNA using the glycan array from the CFG, which has a limited number of different sialic acid derivatives, indicated that SNA has high binding activity toward Sia␣2-6Gal␤1,4GlcNAc-containing glycans (34).…”

Special features of the 2009 pandemic swine-origin influenza A H1N1 hemagglutinin and neuraminidase

“…HA and NA receptor specificities likely play an integral role in determining the basis for influenza host specificity. In general, avian hosts primarily contain α2,3 linked sialic acid receptors and avian influenza virus preferentially binds the α2,3 receptor, however the upper respiratory tract of humans contains primarily α2,6 linked sialic acid receptors [15][16][17]. This may explain why human influenza viruses preferentially bind the α2,6 receptor and is considered a major reason why avian influenza virus is not highly transmissible in humans.…”

“…This may explain why human influenza viruses preferentially bind the α2,6 receptor and is considered a major reason why avian influenza virus is not highly transmissible in humans. Swine contain both α2,3 and α2,6 linked sialic acid receptors in their respiratory system and possess a less complex immune system than humans, which may explain why they are more susceptible to infection by avian and human strains of influenza and why swine influenza viruses may easily evolve the ability to bind the human α2,6 receptor [15][16][17]. The recent 2009 pandemic H1N1 is the first pandemic influenza re-assortment virus with a primarily swine-influenza origin, which is a major reason why it has caused great concern [18][19][20][21].…”