The effects of modified sialic acids on mucus and erythrocytes on influenza A virus HA and NA functions

Karen N. Barnard; Brynn K. Alford-Lawrence; David W. Buchholz; Brian R. Wasik; Justin R. LaClair; Hai Yu; Rebekah Honce; Stefan Ruhl; Petar Pajic; Erin K. Daugherity; Xi Chen; Stacey L. Schultz-Cherry; Hector C. Aguilar; Ajit Varki; Colin R. Parrish

The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. . https://doi.org/10.1101/800300 doi: bioRxiv preprint NA types. Acetylation and Neu5Gc modifications were also inhibitory for HA binding, with soluble HA-Fc sourced from different H1N1 and H3N2 IAV strains showing significantly lower binding to these forms compared to unmodified Neu5Ac in an ELLA assay. (59, 71) , and is seen in the balance between the activities of the HA and NA for the α2-3 and α2-6-linked Sia (71, 72) . Incubation of virus with the wild-type mouse serum 405 (>80% Neu5Gc) compared to the serum of CMAH -/mice (100% Neu5Ac) also showed varying effects. Inhibition by WT serum was seen only for pH1N1 virus, while Victoria H3N2 and PR8 H1N1 were inhibited by both sera. This could confirm previous findings that the density of Sia on these serum proteins is the strongest inhibitory factor rather than the type of modified Sia present, as shown for incubation with horse serum (73). However, the variable results for 410 different viruses may indicate variation in sensitivity to Neu5Gc between strains that requires further investigation. It would also be worthwhile comparing inhibition of IAV strains adapted to different host species, particularly species with higher levels of modified Sia present in their respiratory tracts such as horses and pigs.