vRNA-vRNA interactions in influenza A virus HA vRNA packaging.
vRNA-vRNA interactions in influenza A virus HA vRNA packaging.
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甲型流感病毒 HA vRNA 包装中的 vRNA-vRNA 相互作用。
DOI：
10.1101/2020.01.15.907295
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
T.
中科院分区：
文献类型：
--
作者：
Miyamoto;S.;Muramoto;Y.;Shindo;K.;Fujita;Y.;Morikawa;T.;Tamura;R.;Gilmore;J.L.;Nakano;M.; Noda;T.
甲型流感病毒的基因组由八个单链负义 RNA 片段 (vRNA) 组成。八种不同的 vRNA 被选择性地包装到后代病毒颗粒中。这一过程可能涉及 vRNA 之间通过位于 vRNA 3' 和 5' 末端编码区的片段特异性包装信号进行的特定相互作用。为了识别在基因组包装过程中与血凝素 (HA) vRNA 相互作用的 vRNA，我们生成了一种突变病毒 HA 5m2，它在 HA vRNA 的 5' 包装信号区域具有五个沉默突变。 HA 5m2病毒在HA vRNA掺入方面存在特定缺陷，从而降低了病毒复制效率。在细胞中连续传代后，病毒在 HA 和 PB2 vRNA 的 5' 末端包装信号区域获得了额外的突变。这些突变有助于病毒生长和 HA vRNA 包装效率的恢复。体外证实了 HA 和 PB2 vRNA 5' 端之间的直接 RNA-RNA 相互作用。我们的结果表明，HA vRNA 与 PB2 vRNA 通过其包装信号区域直接相互作用对于选择性基因组包装非常重要，并通过基因重配增强我们对大流行性流感病毒出现的了解。
The genome of the influenza A virus is composed of eight single-stranded negative-sense RNA segments (vRNAs). The eight different vRNAs are selectively packaged into progeny virions. This process likely involves specific interactions among vRNAs via segment-specific packaging signals located in the 3’ and 5’ terminal coding regions of vRNAs. To identify vRNA(s) that interact with hemagglutinin (HA) vRNA during genome packaging, we generated a mutant virus, HA 5m2, which possessed five silent mutations in the 5’ packaging signal region of HA vRNA. The HA 5m2 virus had a specific defect in HA vRNA incorporation, which reduced the viral replication efficiency. After serial passaging in cells, the virus acquired additional mutations in the 5’ terminal packaging signal regions of both HA and PB2 vRNAs. These mutations contributed to recovery of viral growth and packaging efficiency of HA vRNA. A direct RNA-RNA interaction between the 5’ ends of HA and PB2 vRNAs was confirmedin vitro. Our results indicate that direct interactions of HA vRNA with PB2 vRNA via their packaging signal regions are important for selective genome packaging and enhance our knowledge on the emergence of pandemic influenza viruses through genetic reassortment.