Receptor binding properties of human and animal H1 influenza virus isolates

It has been previously reported that several human H1 influenza viruses isolated prior to 1956, in contrast to human H3 isolates which are quite specific for SAα2,6Gal sequences, apparently recognize both SAα2,3Gal and SAα2,6Gal sequences (Rogers, G. N., and Paulson, J. C., Virology 127, 361–373,1983). In this report human H1 isolates representative of two epidemic periods, from 1934 to 1957 and from 1977 to 1986, and H1 influenza isolated from pigs, ducks, and turkeys were compared for their ability to utilize sialyloligosaccharide structures containing terminal SAα2,3Gal or SAα2,6Gal sequences as receptor determinants. Five of the eight human isolates from the first epidemic period recognize both SAα2,3Gal and SAα2,6Gal linkages, in agreement with our previous results. Of the remaining three strains, all isolated towards the end of the first epidemic, two appear to prefer SAα2,6Gal sequences while the third preferentially binds SAα2,3Gal sequences. In contrast to the early isolates, 11 of 13 human strains isolated during the second epidemic period preferentially bind SAα2,6Gal containing oligosaccharides. On the basis of changes in receptor binding associated with continued passage in the laboratory for some of these later strains, it seems likely that human H1 isolates preferentially bind SAα2,6Gal sequences in nature, and that acquisition of SAα2,3Gal-binding is associated with laboratory passage. Influenza H1 viruses isolated from pigs were predominantly SAα2,6Gal-specific while those isolated from ducks were primarily SAαl2,3Gal-specific. Thus, as has been previously reported for H3 influenza isolates, receptor specificity for influenza H1 viruses appears to be influenced by the species from which they were isolated, human isolates binding preferentially to SAα2,6Gal-containing oligosaccharides while those isolated from ducks prefer SAα2,3Gal-containing oligosaccharides. However, unlike the SAα2,6Gal-specific H3 isolates, binding to cell surface receptors by the H1 influenza viruses is not sensitive to inhibition by horse serum glycoproteins, regardless of their receptor specificity. These results suggest that, while the H1 and H3 hemagglutinins appear to be subject to similar host-derived selective pressures, there appear to be certain fundamental differences in the detailed molecular interaction of the two hemagglutinins with their sialyloligosaccharide receptor determinants.