GLYCOSYLATION AFFECTS CLEAVAGE OF AN H5N2 INFLUENZA-VIRUS HEMAGGLUTININ AND REGULATES VIRULENCE
GLYCOSYLATION AFFECTS CLEAVAGE OF AN H5N2 INFLUENZA-VIRUS HEMAGGLUTININ AND REGULATES VIRULENCE
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DOI：
10.1073/pnas.84.1.36
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发表时间：
1987-01-01
影响因子：
11.1
通讯作者：
WEBSTER, RG
中科院分区：
文献类型：
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作者：
DESHPANDE, KL;FRIED, VA;WEBSTER, RG
基于对来自强毒和无毒力A/鸡/宾夕法尼亚/83流感病毒的血凝素（HA）基因的核苷酸序列分析，先前假设获得毒力与导致糖基化位点丢失的点突变相关。由于在HA分子的该区域中有两个潜在的糖基化位点，并且由于不同菌株的HA中的所有Asn-Xaa-Thr/Ser序列不一定是糖基化的，因此关于这些位点中的任一个是否被糖基化的问题仍然是开放的。我们现在提供的直接证据表明，位点特异性糖基化影响流感病毒HA的切割，从而影响毒力。我们已经确定了糖基化位点上的HA 1亚基从毒力和毒力株分离的蛋白质的直接结构分析。我们的研究结果表明，在糖基化之间的有毒和无毒菌株的HA 1的唯一区别是缺乏一个天冬酰胺连接的碳水化合物上的有毒HA 1多肽残基11。此外，我们表明，无毒和毒性病毒的HA 1在一个潜在的网站没有糖基化，而所有其他网站含有碳水化合物。强毒株的无毒回复突变体的HA 1的氨基酸序列分析证实了这些发现。
Based on nucleotide sequence analysis of the hemagglutinin (HA) gene from the virulent and avirulent A/chicken/Pennsylvania/83 influenza viruses, it was previously postulated that acquisition of virulence was associated with a point mutation that resulted in loss of a glycosylation site. Since are two potential glycosylation sites in this region of the HA molecule and since all Asn-Xaa-Thr/Ser sequences in the HAs of different strains are not necessarily glycosylated, the question remained open as to whether either one of these sites was glycosylated. We now provide direct evidence that a site-specific glycosylation affects cleavage of the influenza virus HA and thus virulence. We have identified the glycosylation sites on the HA1 subunit from the virulent and a virulent strains by direct structural analysis of the isolated proteins. Our results show that the only difference in glycosylation between the HA1s of the virulent and avirulent strains is the lack of an asparagine-linked carbohydrate on the virulent HA1 polypeptide at residue 11. Further, we show that the HA1s of both the avirulent and virulent viruses are not glycosylated at one potential site, while all other sites contain carbohydrate. Amino acid sequence analysis of the HA1 of an avirulent revertant of the virulent strain confirmed these findings.