Adaptation of a Duck Influenza A Virus in Quail

Division of Virology, Department of Microbiology and Immunology, University of Tokyo, Shirokanedai, Minato-ku, Tokyo, Japan.
Journal of Virology (Impact Factor: 4.44). 11/2011; 86(3):1411-20. DOI: 10.1128/JVI.06100-11
Source: PubMed


Quail are thought to serve as intermediate hosts of influenza A viruses between aquatic birds and terrestrial birds, such as chickens, due to their high susceptibility to aquatic-bird viruses, which then adapt to replicate efficiently in their new hosts. However, does replication of aquatic-bird influenza viruses in quail similarly result in their efficient replication in humans? Using sialic acid-galactose linkage-specific lectins, we found both avian (sialic acid-α2-3-galactose [Siaα2-3Gal] linkages on sialyloligosaccharides)--and human (Siaα2-6Gal)-type receptors on the tracheal cells of quail, consistent with previous reports. We also passaged a duck H3N2 virus in quail 19 times. Sequence analysis revealed that eight mutations accumulated in hemagglutinin (HA) during these passages. Interestingly, many of the altered HA amino acids found in the adapted virus are present in human seasonal viruses, but not in duck viruses. We also found that stepwise stalk deletion of neuraminidase occurred during passages, resulting in reduced neuraminidase function. Despite some hemagglutinin mutations near the receptor binding pocket, appreciable changes in receptor specificity were not detected. However, reverse-genetics-generated viruses that possessed the hemagglutinin and neuraminidase of the quail-passaged virus replicated significantly better than the virus possessing the parent HA and neuraminidase in normal human bronchial epithelial cells, whereas no significant difference in replication between the two viruses was observed in duck cells. Further, the quail-passaged but not the original duck virus replicated in human bronchial epithelial cells. These data indicate that quail can serve as intermediate hosts for aquatic-bird influenza viruses to be transmitted to humans.

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    • "Claas et al. (1998) suggested early on that the size and shape of glycan receptors, rather than the specific linkage type, are important determinants for human adaptation of influenza A viruses by using HA-glycan conformational analysis and glycan-binding assays. Until now, several researchers have found that human-adapted viruses prefer to bind with longer oligosaccharide chains (Kumari et al., 2007; Stevens, et al., 2008; Shriver et al., 2009; Viswanathan et al., 2010; Chen et al., 2012; Yamada et al., 2012). Crystal structure analysis has revealed that human H3 HA has a wider receptor-binding pocket than does avian H5 HA. "
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