Critical role of segment-specific packaging signals in genetic reassortment of influenza A viruses
Critical role of segment-specific packaging signals in genetic reassortment of influenza A viruses
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DOI：
10.1073/pnas.1308649110
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发表时间：
2013-10-01
影响因子：
11.1
通讯作者：
Moules, Vincent
中科院分区：
文献类型：
--
作者：
Essere, Boris;Yver, Matthieu;Moules, Vincent
甲型流感病毒基因组的片段化特性使得当两种或多种流感病毒感染同一细胞时可以交换基因片段，但对这一过程的基本规则知之甚少。在这里，我们研究了最初从人类分离的A/莫斯科/10/99（H3 N2，MO）病毒和禽A/芬奇/英格兰/2051/91（H5 N2，EN）病毒之间的遗传重配，发现这一过程是强烈的偏见。重要的是，禽HA片段从未单独进入MO遗传背景，而是总是伴随着禽PA和M片段。将HA（MO）的5'和3'包装序列引入HA（EN）骨架中允许嵌合病毒RNA（vRNA）有效地掺入MO遗传背景中。此外，迫使禽M片段的掺入或将五个沉默突变引入人M片段足以驱动禽HA片段共掺入MO遗传背景中。这些沉默突变也强烈影响了重组病毒的基因型。两者合计，我们的研究结果表明，包装信号是至关重要的遗传重配和次优的vRNA包装信号之间的兼容性，这是检测只有当vRNA竞争包装，限制了这一进程。
The fragmented nature of the influenza A genome allows the exchange of gene segments when two or more influenza viruses infect the same cell, but little is known about the rules underlying this process. Here, we studied genetic reassortment between the A/Moscow/10/99 (H3N2, MO) virus originally isolated from human and the avian A/Finch/England/2051/91 (H5N2, EN) virus and found that this process is strongly biased. Importantly, the avian HA segment never entered the MO genetic background alone but always was accompanied by the avian PA and M fragments. Introduction of the 5' and 3' packaging sequences of HA(MO) into an otherwise HA(EN) backbone allowed efficient incorporation of the chimerical viral RNA (vRNA) into the MO genetic background. Furthermore, forcing the incorporation of the avian M segment or introducing five silent mutations into the human M segment was sufficient to drive coincorporation of the avian HA segment into the MO genetic background. These silent mutations also strongly affected the genotype of reassortant viruses. Taken together, our results indicate that packaging signals are crucial for genetic reassortment and that suboptimal compatibility between the vRNA packaging signals, which are detected only when vRNAs compete for packaging, limit this process.