Hierarchy among viral RNA (vRNA) segments in their role in vRNA incorporation into influenza A virions
Hierarchy among viral RNA (vRNA) segments in their role in vRNA incorporation into influenza A virions
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DOI：
10.1128/jvi.80.5.2318-2325.2006
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发表时间：
2006-03-01
影响因子：
5.4
通讯作者：
Kawaoka, Y
中科院分区：
文献类型：
--
作者：
Muramoto, Y;Takada, A;Kawaoka, Y
甲型流感病毒的基因组包括8个负链RNA片段。虽然所有八个片段都必须存在于细胞中才能有效地进行病毒复制，但这些病毒RNA （vRNA）片段被整合到病毒粒子中的机制尚不完全清楚。我们最近发现，A/WSN/33的HA、NA和NS vRNA片段编码区两端的序列在这些vRNA并入病毒粒子中起重要作用。为了类似地鉴定该菌株的PB2、PB1和PA vRNAs中对其结合至关重要的区域，我们生成了一系列突变vRNAs，这些突变vRNAs具有绿色荧光蛋白基因，两侧分别是各自片段的部分编码区和非编码区。对于所有三个聚合酶片段，其编码区末端的缺失降低了它们的病毒粒子整合效率。更重要的是，这些区域不仅影响其所在部分的合并，而且对其他部分的合并也很重要。这种作用在PB2 vRNA中最为明显。这些发现表明vRNA在病毒粒子整合过程中存在层次关系，并可能暗示在病毒组装过程中vRNA在片段间存在关联。
The genome of influenza A viruses comprises eight negative-strand RNA segments. Although all eight segments must be present in cells for efficient viral replication, the mechanism(s) by which these viral RNA (vRNA) segments are incorporated into virions is not fully understood. We recently found that sequences at both ends of the coding regions of the HA, NA, and NS vRNA segments of A/WSN/33 play important roles in the incorporation of these vRNAs into virions. In order to similarly identify the regions of the PB2, PB1, and PA vRNAs of this strain that are critical for their incorporation, we generated a series of mutant vRNAs that possessed the green fluorescent protein gene flanked by portions of the coding and noncoding regions of the respective segments. For all three polymerase segments, deletions at the ends of their coding regions decreased their virion incorporation efficiencies. More importantly, these regions not only affected the incorporation of the segment in which they reside, but were also important for the incorporation of other segments. This effect was most prominent with the PB2 vRNA. These findings suggest a hierarchy among vRNA segments for virion incorporation and may imply intersegment association of vRNAs during virus assembly.