आणविक और आनुवंशिक चिकित्सा

Differences in influenza virus receptors in chickens and ducks: Implications for interspecies transmission

Abstract

Suresh V Kuchipudi, Rahul Nelli, Gavin A White, Maureen Bain, Kin Chow Chang and Stephen Dunham

Avian influenza viruses are considered to be key contributors to the emergence of human influenza pandemics. A major determinant of infection is the presence of virus receptors on susceptible cells to which the viral haemagglutinin is able to bind. Avian viruses preferentially bind to sialic acid E2,3-galactose (SAE2,3-Gal) linked receptors, whereas human strains bind to sialic acid E2,6-galactose (SAE2,6-Gal) linked receptors. While ducks are the major reservoir for influenza viruses, they are typically resistant to the effects of viral infection, in contrast to the frequently severe disease observed in chickens. In order to understand whether differences in receptors might contribute to this observation, we studied the distribution of influenza receptors in organs of ducks and chickens using lectin histochemistry with linkage specific lectins and receptor binding assays with swine and avian influenza viruses. Although the intestinal epithelial cells of both species expressed only SAE2,3-Gal receptors, we found widespread presence of both SAE2,6-Gal and SAE2,3-Gal receptors in many organs of both chickens and ducks. Co-expression of both receptors may allow infection of cells with both avian and human viruses and so present a route to genetic reassortment. There was a marked difference in the primary receptor type in the trachea of chickens and ducks. In chicken trachea, SAE2,6-Gal was the dominant receptor type whereas in ducks SAE2,3-Gal receptors were most abundant. This suggests that chickens could be more important as an intermediate host for the generation of influenza viruses with increased ability to bind to SAE2,6-Gal receptors and thus greater potential for infection of humans. Chicken tracheal and intestinal epithelial cells also expressed a broader range of SAE2,3-Gal receptors (both G(1-4)GlcNAc and G(1-3)GalNAc subtypes) in contrast to ducks, which suggests that they may be able to support infection with a broader range of avian influenza viruses.