Differences in the biological phenotype of low-yielding (L) and high-yielding (H) variants of swine influenza virus A/NJ/11/76 are associated with their different receptor-binding activity

Differences in the biological phenotype of low-yielding (L) and high-yielding (H) variants of swine influenza virus A/NJ/11/76 are associated with their different receptor-binding activity
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DOI:
10.1006/viro.1998.9274
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发表时间:
1998-08-01
期刊:
影响因子:
3.7
通讯作者:
Kilbourne, ED
Kilbourne, ED
中科院分区:
医学3区
文献类型:
--
作者:
Gambaryan, AS;Matrosovich, MN;Kilbourne, ED

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比较了A/SW/NJ/11/76流感病毒的低毒株(L株)和高产株(H株)在鸡胚蛋和鸡胚细胞上的生长特性,以及它们与鸡胚尿囊膜细胞、鸡胚尿囊膜细胞和猪气管细胞膜组分的亲和力,以及对含唾液酸大分子和单价唾液酸苷的亲和力。我们发现,在MDCK细胞和卵子感染过程中,L突变株的后代仍然以细胞相关为主,而与H突变株相比,L突变株在尿囊液或培养液中的积累明显慢于H突变株。病毒在MDCK细胞单层和尿囊膜上形成的感染灶的可视化显示,L主要在细胞之间传播,而H的传播涉及到病毒后代释放到溶液中,并通过液体的对流在细胞单层上迅速分布。在结合实验中,L对细胞膜、神经节苷脂和唾液酸糖蛋白的亲和力明显高于H,而对单价唾液酸化合物的亲和力与H相当。与H不同的是,L与硫酸葡聚糖结合强烈。所获得的数据表明,以前报道的L和H生物学表型的所有区别[基尔伯恩,E.D.,泰勒,A.H.,惠特克,C.W.,萨海,R.,和卡顿,A.(1988)血凝素多态是猪流感病毒低产和高产表型的基础。程序娜塔莉。阿卡德。SCI USA85,7782-7785]可以合理地解释为L变异体更强烈地结合到靶细胞表面,并且这种效应主要是由于增强的静电相互作用。(C)1998年学术出版社。
Low- (L) and high-yielding (H) variants of A/sw/NJ/11/76 influenza virus were compared for their growth properties in embryonated chicken eggs and MDCK cells and for their binding affinity for the membrane fractions prepared from cells of the chicken embryo allantoic membrane, MDCK, and swine tracheal cells, as well as for soluble sialic acid containing macromolecules and monovalent sialosides. We have shown, that during infection in MDCK cells and in eggs, the progeny of the L variant remain predominantly cell associated, in contrast to those of H. As a result, accumulation of the L mutant in allantoic or culture fluid is significantly slowed in comparison with the H variant. Visualization of the infectious foci formed by the viruses in MDCK cell monolayers and on the allantoic membrane revealed that L spreads predominantly from cell to cell, while the spread of H involves release of the virus progeny into solution and its rapid distribution over the cell monolayer via convectional flow of the liquid. In the binding assays, L displayed significantly higher binding affinity than H for cellular membranes, gangliosides, and sialylglycoproteins, however, the affinity of the variants for the monovalent sialic acid compounds was comparable. Unlike H, L bound strongly to dextran sulfate. The data obtained suggest that all distinctions of the L and H biological phenotypes reported previously [Kilbourne, E. D., Taylor, A. H., Whitaker, C. W., Sahai, R., and Caton, A. (1988) Hemagglutinin polymorphism as the basis for low-and high-yield phenotypes of swine influenza virus. Proc. Natl. Acad. Sci USA 85, 7782-7785] could be rationally explained by a more avid binding of the L variant to the surface of target cells, and that this effect is mainly due to enhanced electrostatic interactions. (C) 1998 Academic Press.