Flu

Biography

Biography: Wen Tian Chen

Abstract

We undertook a detailed investigation of the distribution and the evolutionary pattern of the potential glycosites (N-glycosylation site) in the envelope glycoproteins of Influenza Virus. Two glycosites were located at HA0 cleavage sites (e.g., the 27N in H1) and fusion peptides (e.g., the 498N in H1) and were strikingly conserved in all HA subtypes. Two to four conserved glycosites were found in the stalk domain of NA, but these are affected by the deletion of specific stalk domain sequences. Another highly conserved glycosite (e.g., the 146N in N2) appeared at the top center of tetrameric global domain, while the others glycosites were distributed around the global domain. We further focus on the H5N1 virus and conclude that the glycosites in H5N1 have become more complicated in HA and less influential in NA in the last seven years. Two glycosylation sites, 158N and 169N, which located near to the receptor-binding domains (RBDs) of HA, also participated in receptor recognition. We attempted to construct a serial H5N1 HA models including diverse glycosylated HAs to simulate the binding process with various SA receptors in silico. As the SA(Sialic Acid)-a-2,3-Gal(Galactose) and SA-a-2,6-Gal sialoglycan adopted two distinctive topologies, straight and fishhook-like, respectively, the presence of N-glycans at 158N would decrease the affinity of HA for all of the receptors, particularly SA-a-2,6-Gal analogs. The steric clashes of the huge glycans shown at another glycosylation site, 169N, located on an adjacent HA monomer, would be more effective in preventing the binding of SA-a-2,3-Gal analogs.