Effects of egg-adaptation on the receptor-binding properties of human influenza A and B viruses
Effects of egg-adaptation on the receptor-binding properties of human influenza A and B viruses
复制标题
DOI：
10.1006/viro.1999.9732
复制
发表时间：
1999-06-05
期刊：
影响因子：
3.7
通讯作者：
Matrosovich, MN
中科院分区：
文献类型：
--
作者：
Gambaryan, AS;Robertson, JS;Matrosovich, MN
人流感病毒在胚化鸡蛋（CE）中的繁殖导致在血凝素（HA）分子受体结合位点附近氨基酸取代的变异选择。为了评估这些取代使人病毒在CE中生长的机制，我们研究了10株人流感A （H1N1, H3N2）和B株在MDCK细胞中分离和繁殖的结合，以及它们的卵适应对应物对细胞膜、神经节苷、唾液糖蛋白和唾液寡糖的制备。所有适应卵子的变异与不适应的菌株的不同之处是，它们与CE的绒毛膜-尿囊（CAM）细胞的质膜结合增加，并且能够与CAM神经节苷类结合。此外，尿囊液中对抑制剂的亲和力没有降低。这些发现表明，由于人类流感病毒与CAM细胞上的受体结合效率低下，它们在CE中的生长受到限制，神经节苷类在病毒结合和/或渗透中发挥重要作用。ega-适应性取代对病毒受体结合特性的影响包括：(i)增强病毒与末端Sia(alpha 2-3)Gal决定因子的结合（在H1N1株的HA位置190、225和H3N2株的HA位置186取代）；（ii）与含有Sia（α 2-3Gal）的受体较远部位的位位干扰减少（H1 HA的163位和B HA的187位的糖基化位点丢失）；（iii）由于HA顶端的带电取代而增强了与带负电荷分子的离子相互作用[187,189,190 （H1）和145,156 (H3)]。与Sia(α 2-3) gal末端受体结合增强的同时，所有卵适应变异都降低了它们对马巨球蛋白的亲和力，马巨球蛋白是一种携带末端6'-唾液酰（n -乙酰乳胺）-片段的糖蛋白。(C) 1999学术出版社。
Propagation of human influenza viruses in embryonated chicken eggs (CE) results in the selection of variants with amino acid substitutions near the receptor-binding site of the hemagglutinin (HA) molecule. To evaluate the mechanisms by which these substitutions enable human virus growth in CE, we studied the binding of 10 human influenza A (H1N1, H3N2) and B strains, isolated and propagated solely in MDCK cells, and of their egg-adapted counterparts to preparations of cellular membranes, gangliosides, sialylglycoproteins, and sialyloligosaccharides. All egg adapted variants differed from nonadapted strains by increased binding to the plasma membranes of chorio-allantoic (CAM) cells of CE and by the ability to bind to CAM gangliosides. In addition, there was no decrease in affinity for inhibitors within allantoic fluid. These findings indicate that growth of human influenza viruses in CE is restricted because of their inefficient binding to receptors on CAM cells and that gangliosides can play an important role in virus binding and/or penetration. The effects of the ega-adaptation substitutions on the receptor-binding properties of the viruses include (i) enhancement of virus binding to the terminal Sia(alpha 2-3)Gal determinant (substitutions in HA positions 190, 225 of H1N1 strains and in position 186 of H3N2 strains); (ii) a decrease of steric interference with more distant parts of the Sia(alpha 2-3Gal)-containing receptors (a loss of glycosylation sites in positions 163 of H1 HA and 187 of type B HA); and (iii) enhanced ionic interactions with the negatively charged molecules due to charged substitutions at the tip of the HA [187, 189, 190 (H1), and 145, 156 (H3)]. Concomitantly with enhanced binding to Sia(alpha 2-3)Gal-terminated receptors, all egg-adapted variants decreased their affinity for equine macroglobulin, a glycoprotein bearing terminal 6'-sialyl(N-acetyllactosamine)-moieties. (C) 1999 Academic Press.