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

When compared directly, NA VLPs removed 5-12% of Neu5Gc compared to their activities on Neu5Ac (Fig. 6C) . Again, variability was seen between NA VLPs here, with N7 having the 275 lowest activity against Neu5Gc compared to Neu5Ac and N9 having the most. There was also variability in cleavage activity between NA from different strains as well, as seen in the variable amount of Neu5Ac removed by the NA VLPs in Figure 6B , but it is unclear whether this difference is due to the intrinsic activates of the NAs when expressed as VLPs or to innate differences in the specific activities of each NA enzyme, or both. It is clear, however, that O-280 acetyl and Neu5Gc modifications inhibit the activities of many different IAV NA and of NeuA, and that multiple modifications, such as di-O-acetyl modifications, or Neu5Gc that is also Oacetylated, were even more inhibitory, showing high resistance to most of the viral and bacterial NAs tested here.