DIFFERENCES IN THE BIOLOGICAL PHENOTYPE OF LOW-YIELDING (L) AND HIGH-YIELDING (H) VARIANTS OF SWINE INFLUENZA-VIRUS A NJ/11/76 ARE ASSOCIATED WITH THEIR DIFFERENT RECEPTOR-BINDING ACTIVITY/

Low- (L) and high-yielding (H) variants of A/sw/NJ/11/76 influenza vir us were compared for their growth properties in embryonated chicken eg gs and MDCK cells and for their binding affinity for the membrane frac tions prepared from cells of the chicken embryo allantoic membrane, MD CK, and swine tracheal cells, as well as for soluble sialic acid conta ining macromolecules and monovalent sialosides. We have shown, that du ring infection in MDCK cells and in eggs, the progeny of the L variant remain predominantly cell associated, in contrast to those of H. As a result, accumulation of the L mutant in allantoic or culture fluid is significantly slowed in comparison with the H variant. Visualization oi: the infectious foci formed by the viruses in MDCK cell monolayers and on the allantoic membrane revealed that L spreads predominantly fr om cell to cell, while the spread of H involves release of the virus p rogeny into solution and its rapid distribution over the cell monolaye r via convectional flow of the liquid. In the binding assays, L displa yed significantly higher binding affinity than H for cellular membrane s, gangliosides, and sialylglycoproteins, however, the affinity of the variants for the monovalent sialic acid compounds was comparable. Unl ike H, L bound strongly to dextran sulfate. The data obtained suggest that all distinctions of the L and H biological phenotypes reported pr eviously [Kilbourne, E. D., Taylor, A. H., Whitaker, C. W., Sahai, R., and Caton, A. (1988) Hemagglutinin polymorphism as the basis for low- and high-yield phenotypes of swine influenza virus. Proc. Natl. Acad. Sci USA 85, 7782-7785] could be rationally explained by a more avid bi nding of the L variant to the surface of target cells, and that this e ffect is mainly due to enhanced electrostatic interactions. (C) 1998 A cademic Press.