Elongation of the N-acyl side chain of sialic acids in MDCK II cells inhibits influenza A virus infection
Elongation of the N-acyl side chain of sialic acids in MDCK II cells inhibits influenza A virus infection
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DOI：
10.1006/bbrc.1998.9650
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发表时间：
1998-12-18
影响因子：
3.1
通讯作者：
Pawlita, M
中科院分区：
文献类型：
--
作者：
Keppler, OT;Herrmann, M;Pawlita, M
甲型流感病毒与唾液酸化受体组分的相互作用是最佳表征的配体-受体相互作用之一。我们用三种不同的N-酰基修饰的唾液酸前体类似物N-丙酰基、N-丁酰基或N-戊酰基D-甘露糖胺预处理MDCK II宿主细胞。细胞唾液酸生物合成产生18-35%的新的，修饰的唾液酸细胞表面糖缀合物，N-丙酰基，N-丁酰基或N-戊酰基神经氨酸，分别。唾液酸的N-酰基基团的延长导致对甲型流感病毒（菌株X31）结合和随后感染的抑制高达80%。相反，在这些细胞中，水疱性口炎病毒的唾液酸非依赖性感染不受影响。基于与唾液酸乳糖复合的甲型流感病毒血凝素的晶体结构的分子建模研究表明血凝素与疏水性延长的N-酰基结合的空间位阻。我们提出生物合成唾液酸修饰结合分子建模是进一步分析甲型流感病毒-受体相互作用的有力工具，（C）1998学术出版社。
The interaction of influenza A virus with sialyated receptor components is one of the best characterized ligand-receptor interactions. We pretreated MDCK II host cells with three different N-acyl-modified sialic acid precursor analogues, N-propanoyl, N-butanoyl or N-pentanoyl D-mannnosamine. Cellular sialic acid biosynthesis yielded 18-35% of new, modified sialic acids on cell surface glycoconjugates, N-propanoyl, N-butanoyl or N-pentanoyl neuraminic acid, respectively. The elongation of the N-acyl group of sialic acids resulted in an inhibition of influenza A virus (strain X31) binding and subsequent infection of up to 80%. In contrast, the sialic acid-independent infection of vesicular stomatitis virus was unaffected in these cells. Molecular modeling studies based on the crystal structure of the influenza A virus hemagglutinin complexed with sialyllactose suggest a steric hindrance of hemagglutinin binding to aliphatically elongated N-acyl groups. We propose that biosynthetic sialic acid modification in conjunction with molecular modeling is a potent tool to further analyze the influenza A virus-receptor interaction, (C) 1998 Academic Press.