Selective incorporation of influenza virus RNA segments into virions
Selective incorporation of influenza virus RNA segments into virions
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DOI：
10.1073/pnas.0437772100
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发表时间：
2003-02-18
影响因子：
11.1
通讯作者：
Kawaoka, T
中科院分区：
文献类型：
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作者：
Fujii, Y;Goto, H;Kawaoka, T
甲型流感病毒的基因组由八个病毒RNA（vRNA）片段组成。虽然所有八个vRNA片段的产物必须存在于病毒复制中，但对负责将这些片段并入病毒体的机制知之甚少。已经提出了两种模型用于产生含有八个vRNA片段的感染性病毒体。随机掺入模型假设所有vRNA具有共同的结构特征，使任何vRNA组合都能随机掺入病毒体。选择性掺入模型预测每个vRNA片段中存在特定结构，导致一组八个vRNA片段掺入病毒体中。在这里，我们证明了八个不同的vRNA片段必须存在有效的病毒体形成和编码区内的序列（因此独特的）的神经氨酸酶vRNA具有驱动该片段纳入病毒体的信号。这些发现表明单个vRNA片段的独特贡献，因此表明vRNA募集到病毒体中的选择性（而不是随机）机制。神经氨酸酶vRNA掺入信号和其他有待鉴定的信号应该为疫苗生产中流感病毒的减毒和新的抗病毒药物的设计提供有吸引力的靶点。
The genome of influenza A virus is comprised of eight viral RNA (vRNA) segments. Although the products of all eight vRNA segments must be present for viral replication, little is known about the mechanism(s) responsible for incorporation of these segments into virions. Two models have been proposed for the generation of infectious virions containing eight vRNA segments. The random-incorporation model assumes a common structural feature in all the vRNAs, enabling any combination of vRNAs to be incorporated randomly into virions. The selective-incorporation model predicts the presence of specific structures in each vRNA segment, leading to the incorporation of a set of eight vRNA segments into virions. Here we demonstrate that eight different vRNA segments must be present for efficient virion formation and that sequences within the coding region of (and thus unique to) the neuraminidase vRNA possess a signal that drives incorporation of this segment into virions. These findings indicate a unique contribution from individual vRNA segments and thus suggest a selective (rather than random) mechanism of vRNA recruitment into virions. The neuraminidase vRNA incorporation signal and others yet to be identified should provide attractive targets for the attenuation of influenza viruses in vaccine production and the design of new antiviral drugs.