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

host infection, and the specific linkages of Sia to the underlying glycan chain have long been known to influence host tropism (36) . We examined the effects of O-acetyl and Neu5Gc modifications on IAV HA binding, NA cleavage, and on infection, and found differences among 385 the IAV strains examined. All the different IAV NA tested showed preferential removal of Neu5Ac over any modified Sia form. Cleavage by N1, N7, and N9 were strongly inhibited by mono-acetylated Sia, while N2 and N3 were less affected. All NA had much lower activity against Neu5Gc, di-acetylated Sia, and particularly against Neu5Gc forms with additional Oacetylations. This confirms previous reports showing or suggesting inhibition of NA cleavage in 390 H1N1 and H3N2 strains (38, 42) , but revealing that there is wide variation of effects on different All rights reserved. No reuse allowed without permission.