Matrosovich M N, Gambaryan A S, Tuzikov A B, Byramova N E, Mochalova L V, Golbraikh A A, Shenderovich M D, Finne J, Bovin N V
Institute of Poliomyelitis and Viral Encephalitides, Russian Academy of Medical Sciences, Moscow Region.
Virology. 1993 Sep;196(1):111-21. doi: 10.1006/viro.1993.1459.
To compare features of the receptor-binding sites (RBSs) of different influenza virus hemagglutinins (HA), binding of a number of synthetic sialic acid (SA) analogs and natural sialosides by a panel of about 30 human influenza A and B virus strains was studied in a competitive ligand binding assay. For all the viruses tested, the N-acetyl group of Neu5Ac, as well as the natural orientation of the carboxylic group at C2 and the hydroxylic group at C4, was essential for binding. Significant type- and subtype-specific differences were observed in virus recognition of asialic parts of sialosides. H1 strains, unlike H3 and type B viruses, were found to bind alpha 2-6-sialyl-N-acetyllactosamine with about an order of magnitude higher affinity than alpha 2-6-sialyllactose (6'SL). The H1 viruses and the H3 strains with Gln in position 226 of HA, but not the H3 strains with Leu-226, bound 6'SL with a lower affinity than alpha 2-3-sialyllactose; this effect correlated clearly with the preferential binding by the former viruses of unsubstituted alpha Neu5Ac compared to methyl alpha-glycoside of Neu5Ac. Thus, differentiation between the types of the SA-Gal linkage by the A viruses appeared to depend, at least partially, upon the recognition by the HA of the first hydrocarbon group of the aglycon. Type B virus strains were distinct in having a lower affinity for the Neu5Ac moiety and in providing a higher contribution of the asialic portions of sialosides to the HA-ligand interactions. The last effects are presumably due to the amino acid insertions in the type B HA surrounding the RBS, which makes the receptor-binding pocket deeper. The results obtained in the present investigation indicate that while the functional groups of Neu5Ac studied are recognized by the RBSs of all influenza viruses, the magnitude of their contribution to the binding energy, as well as the contribution of the asialic portion of the receptor, may vary in dependence upon the virus type, subtype, and strain.
为比较不同流感病毒血凝素（HA）受体结合位点（RBS）的特征，在竞争性配体结合试验中研究了约30株甲型和乙型人流感病毒对多种合成唾液酸（SA）类似物和天然唾液酸苷的结合情况。对于所有测试病毒，Neu5Ac的N - 乙酰基以及C2位羧基和C4位羟基的天然取向对于结合至关重要。在病毒对唾液酸苷去唾液酸部分的识别中观察到显著的型别和亚型特异性差异。与H3和乙型病毒不同，发现H1毒株结合α2 - 6 - 唾液酸基 - N - 乙酰乳糖胺的亲和力比α2 - 6 - 唾液酸乳糖（6'SL）高约一个数量级。HA第226位为Gln的H1病毒和H3毒株，但HA第226位为Leu的H3毒株，结合6'SL的亲和力低于α2 - 3 - 唾液酸乳糖；这种效应与前一类病毒相比Neu5Ac的未取代α - 神经氨酸与Neu5Ac的甲基α - 糖苷优先结合明显相关。因此，甲型病毒对SA - Gal连接类型的区分似乎至少部分取决于HA对苷元第一个烃基的识别。乙型病毒株的不同之处在于对Neu5Ac部分的亲和力较低，并且唾液酸苷的去唾液酸部分对HA - 配体相互作用的贡献更大。后一种效应可能是由于乙型HA中RBS周围的氨基酸插入，使受体结合口袋更深。本研究获得的结果表明虽然所研究的Neu5Ac官能团被所有流感病毒的RBS识别，但其对结合能的贡献大小以及受体去唾液酸部分的贡献可能因病毒类型、亚型和毒株而异。
