Importance of both the coding and the segment-specific noncoding regions of the influenza a virus NS segment for its efficient incorporation into virions
Importance of both the coding and the segment-specific noncoding regions of the influenza a virus NS segment for its efficient incorporation into virions
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DOI：
10.1128/jvi.79.6.3766-3774.2005
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发表时间：
2005-03-01
影响因子：
5.4
通讯作者：
Kawaoka, Y
中科院分区：
文献类型：
--
作者：
Fujii, K;Fujii, Y;Kawaoka, Y
甲型流感病毒基因组由8个单链负义RNA片段组成，每个片段由编码区和非编码区组成。NS片段的非编码区被认为为包装提供信号；然而，我们最近发现，位于血凝素和神经氨酸酶片段两端的编码区对于它们与病毒粒子的结合是重要的。为了更好地理解流感病毒基因组包装的机制，我们试图确定NS病毒RNA(VRNA)的哪些区域是其有效整合到病毒粒子中所必需的。缺失分析表明，3‘编码区的前30个核苷酸是有效掺入NS vRNA的关键，3’片段特异性非编码区的缺失显著减少了NS vRNA对病毒粒子的掺入。此外，3‘NS编码区前30个核苷酸的沉默突变降低了NS片段的掺入效率，并影响了病毒的复制。这些结果表明，片段特异性非编码区与相邻的编码区(特别是3‘端)一起形成了有效包装甲型流感病毒vRNA所需的结构。
The genome of influenza A virus consists of eight single-strand negative-sense RNA segments, each comprised of a coding region and a noncoding region. The noncoding region of the NS segment is thought to provide the signal for packaging; however, we recently showed that the coding regions located at both ends of the hemagglutinin and neuraminidase segments were important for their incorporation into virions. In an effort to improve our understanding of the mechanism of influenza virus genome packaging, we sought to identify the regions of NS viral RNA (vRNA) that are required for its efficient incorporation into virions. Deletion analysis showed that the first 30 nucleotides of the 3' coding region are critical for efficient NS vRNA incorporation and that deletion of the 3' segment-specific noncoding region drastically reduces NS vRNA incorporation into virions. Furthermore, silent mutations in the first 30 nucleotides of the 3' NS coding region reduced the incorporation efficiency of the NS segment and affected virus replication. These results suggested that segment-specific noncoding regions together with adjacent coding regions (especially at the 3' end) form a structure that is required for efficient influenza A virus vRNA packaging.