DIFFERENTIAL PHOSPHORYLATION OF THE NUCLEOPROTEIN OF INFLUENZA-A VIRUSES
DIFFERENTIAL PHOSPHORYLATION OF THE NUCLEOPROTEIN OF INFLUENZA-A VIRUSES
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DOI：
10.1099/0022-1317-70-9-2421
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发表时间：
1989-09-01
影响因子：
3.8
通讯作者：
SCHOLTISSEK, C
中科院分区：
文献类型：
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作者：
KISTNER, O;MULLER, K;SCHOLTISSEK, C
29种不同流感病毒核蛋白分析。A病毒的磷酸肽指纹图谱显示了三种原型模式。第一种是由六到七个磷酸肽组成的复杂模式，另一个相对简单的模式是由两个或三个磷酸肽组成，第三个模式是复杂的，但缺少另外两个模式所共有的主要磷酸肽。磷酸丝氨酸是检测到的唯一标记的磷酸氨基酸。通过比较25株菌株的已知氨基酸序列，可以初步推断其中两个磷酸结合位点(第3位和第473位的丝氨酸残基)。未发现菌株的物种特异性、亚型或分离年份之间的相关性。在感染周期中，指纹发生了显著的变化，表明在病毒增殖的不同阶段，NP发生了微妙的磷酸化和去磷酸化。大多数磷酸肽在代谢上是稳定的，但有一种主要的磷酸肽是在成熟病毒粒子的NP中没有发现的，它具有很高的周转率(可能是第3位的丝氨酸)。佛波醇酯12-十四烷基佛波酯13-乙酸酯对细胞蛋白激酶C的特异性刺激或异喹啉磺酰胺H7的抑制都会显著影响磷肽指纹图谱。H7通过解除对病毒蛋白质合成的管制而特别抑制甲型流感病毒的复制，而不干扰副流感病毒(新城疫病毒)、甲型病毒(塞姆利基森林病毒)或黄病毒(西尼罗河)的繁殖。因此，流感病毒NP的正确磷酸化似乎对流感病毒的复制至关重要。
An analysis of the nucleoprotein (NP) fo 29 different influenza. A viruses by phosphopeptide fingerprinting revealed three prototype patterns. The first, which was a complex pattern consisting fo six to seven phosphopeptides, another which was relatively simple consisted of two or three phosphopeptides, and a third one which was complex but was missing the main phosphopeptide shared by the two other patterns. Phosphoserine was the only labelled phosphamino acid detected. A tentative deduction of two of the phosphate attachment sites (serine residues at positions 3 and 473) could be made by comparison of the known amino acid sequences of the NPs of 25 strains. No correlation was found between species specificity or subtype or year of isolation of the strains. During the infectious cycle the fingerprint underwent signficant changes, indicating subtle phsophorylation and dephosphorylation of the NP at various stages during viral multiplication. Most of the phosphopeptides were metabolically stable; however one major phosphopeptide, which was not found in the NP of mature virions, exhibited a high turnover (presumably serine at position 3). The phosphopeptide fingerprint could be significantly influenced in vivo by the specific stimulation of cellular protein kinase C by the phorbol ester 12-Otetradecanolyphorbol 13-acetate or by its inhibition with the isoquinoline sulphonamide H7. H7 specifically inhibited the replication of influenza A viruses by deregulation of viral protein synthesis without interfering with the multiplication of a parainfluenza virus (Newcastle disease virus), an alphavirus (Semliki Forest virus) or a flavivirus (West nile). Therefore the correct phosphorylation fo the NP of influenza viruses appears to be essential for influenza virus replication.