Receptor Specificity of Influenza A Viruses Correlates with the Agglutination of Erythrocytes from Different Animal Species

Abstract

Despite their uniform ability to bind to oligosaccharide-containing terminal sialic acids, influenza A viruses show differences in receptor specificity. To test whether agglutination of erythrocytes from different animal species could be used to assess the receptor specificity of influenza A viruses, we determined the agglutinating activities of a range of virus strains, including those with known receptor specificities, using erythrocytes from seven animal species. All equine and avian viruses, including those known to recognize N-acetyl and N-glycolyl sialic acid linked to galactose by the alpha2,3 linkage (NeuAc alpha2,3Gal and NeuGc alpha2,3Gal), agglutinated erythrocytes from all of the animal species tested (chickens, ducks, guinea pigs, humans, sheep, horses, and cows). The human viruses, including those known to preferentially recognize NeuAc alpha2,6Gal, agglutinated all but the horse and cow erythrocytes. Fluorescence-activated cell sorting analysis of erythrocytes using linkage-specific lectins [Sambucus nigra agglutinin for sialic acid (SA) alpha2,6Gal and Maackia amurensis agglutinin for SA alpha2,3Gal] showed that both cow and horse erythrocytes contain a large amount of SA alpha2,3Gal-, but virtually no SA2,6Gal-specific lectin-reactive oligosaccharides on the cell surface, while human and chicken erythrocytes contained both types of oligosaccharides. Considering that the majority (>93%) of sialic acid in horse and cow erythrocytes is of the N-glycolyl type, our results suggest that viruses able to agglutinate these erythrocytes (i.e., avian and equine viruses) recognize NeuGc alpha2,3Gal. These findings also show that agglutinating assays with erythrocytes from different animal species would be useful in characterizing the receptor specificity of influenza A viruses.

Identification of amino acid residues of influenza A virus H3 HA contributing to the recognition of molecular species of sialic acid

“…The present work is the first study to show, by using a reverse genetics system, that not only residue 155 but also residue 158 in the HA protein contributes to the recognition of molecular species of sialic acid. In the transmission of IAVs between ducks and other animals including pigs, glycoconjugates containing Neu5Gc in the trachea of the pig and crypt cells of the duck colon may be utilized as a common receptor that avian, swine, and equine IAV can recognize [1,6,14,17]. Our finding will be helpful in understanding the significance of molecular species of sialic acid for viral transmission, host range restriction, and pandemics, leading to useful information for the development of anti-influenza virus agents and surveillance of pandemic potential.…”

Neuraminidase-mediated haemagglutination of recent human influenza A(H3N2) viruses is determined by arginine 150 flanking the neuraminidase catalytic site

“…Fluctuations of the haemagglutination activity of HA have been observed in the past, due to amino acid changes in the HA of influenza A(H3N2) and A(H1N1) viruses that led to the inability to agglutinate chicken erythrocytes [14][15][16]. Because erythrocytes of different animal species contain different oligosaccharide structures on their surface, changes in the receptor specificity of HA of influenza viruses have been shown to correlate with differences in haemagglutination behaviour [17]. However, changes in haemagglutination behaviour do not necessarily affect the ability of influenza viruses to bind to host cells during natural infection, as the nature and density of the oligosaccharides that are present on the surface of erythrocytes do not necessarily reflect those of the glycans present on host cells and tissues.…”

“…Changes in HA affinity to erythrocytes from different species have been observed occasionally since influenza A(H3N2) viruses have been circulating in the human population [14][15][16][17]. Since the early 2000s, several groups have observed changes in the haemagglutination behaviour of influenza A(H3N2) viruses, i.e.…”

Neutrophils Ameliorate Lung Injury and the Development of Severe Disease during Influenza Infection

“…Although specific mutations have been associated with mouse adaptation and multiorgan spread of human isolates (62, 63), we found no conserved changes between isolates of HKx31 from the heart and brain when compared with those from the lungs. Given the well-documented ability of influenza viruses to agglutinate erythrocytes and mammalian cells (64), thrombus formation, cellular injury, and ischemia reported in patients with severe influenza infections (65,66) could also be important pathological sequelae if hemagglutination were to occur in the microvasculature of neutropenic animals.…”