HOST-MEDIATED SELECTION OF INFLUENZA-VIRUS RECEPTOR VARIANTS - SIALIC ACID ALPHA-2,6GAL-SPECIFIC CLONES OF A/DUCK/UKRAINE/1/63 REVERT TO SIALIC ACID-ALPHA-2,3GAL-SPECIFIC WILD-TYPE INOVO

Abstract

Human and animal influenza A isolates of the H3 serotype preferentially bind SA.alpha.2,6-Gal or SA.alpha.2,3-Gal linkages (where SA represents sialic acid), respectively, on cell-surface sialyloligosaccharides. Previously, the selection of SA.alpha.2,3-Gal-specific receptor variants of several human viruses which differed from the parent viruses by a single amino acid at residue 226 of the hemagglutinin, which is located in the receptor binding pocket, was demonstrated. In this report, the selection in the reverse direction was accomplished starting with a SA.alpha.2,3-Gal-specific avian virus, A/duck/Ukraine/1/63 (H3N7), yielding SA.alpha.2,6-Gal-specific variants that exhibit the receptor binding properties characteristic of the human isolates. Selection was again mediated at residue 226 of the hemagglutinin, in this case changing from Gln in the parent virus to Leu in the variants. Although the SA.alpha.2,6-Gal-specific avian virus variants were stable to passage in MDCK cells, they exhibited dramatic reversion to the SA.alpha.2,3-Gal-specific phenotype of the parent virus during a single passage in chicken embryos. This was in contrast to the SA.alpha.2,6-Gal-specific human virus isolates which were stable to passage in both hosts. The reversion of the avian virus variants in eggs provides compelling evidence for host-mediated selection of influenza virus receptor variants.