A conserved influenza A virus nucleoprotein code controls specific viral genome packaging.

A conserved influenza A virus nucleoprotein code controls specific viral genome packaging.
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DOI:
10.1038/ncomms12861
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发表时间:
2016-09-21
影响因子:
16.6
通讯作者:
Juozapaitis, Mindaugas
Juozapaitis, Mindaugas
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Moreira, Etori Aguiar;Weber, Anna;Bolte, Hardin;Kolesnikova, Larissa;Giese, Sebastian;Lakdawala, Seema;Beer, Martin;Zimmer, Gert;Garcia-Sastre, Adolfo;Schwemmle, Martin;Juozapaitis, Mindaugas

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甲型流感病毒(IAV)的8个基因组RNA片段包装成病毒颗粒是由片段特异性包装序列协调的。包装信号如何调节每个RNA片段特异性结合到病毒粒子中,以及其他病毒或宿主因子是否参与这一过程尚不清楚。在这里,我们证明了病毒核蛋白(NP)的不同氨基酸是包装特定RNA片段所必需的。这是通过在常规IAV (SC35M)背景下研究蝙蝠甲型流感样病毒HL17NL10的NP来确定的。保守的SC35M NP残基被HL17NL10 NP残基取代导致RNA包装缺陷的IAV。令人惊讶的是,用HL17NL10 NP残基取代这些保守的SC35M氨基酸导致IAV对特定RNA片段亚群的包装效率发生改变。这表明NP含有一种氨基酸密码,可以指示基因组包装成传染性病毒粒子。甲型流感病毒8个基因组RNA片段的核苷酸序列提供了必要的包装信号,但这些序列如何被识别尚不清楚。在这里,Moreira等人发现了病毒核蛋白中调节RNA片段包装的保守氨基酸。
Packaging of the eight genomic RNA segments of influenza A viruses (IAV) into viral particles is coordinated by segment-specific packaging sequences. How the packaging signals regulate the specific incorporation of each RNA segment into virions and whether other viral or host factors are involved in this process is unknown. Here, we show that distinct amino acids of the viral nucleoprotein (NP) are required for packaging of specific RNA segments. This was determined by studying the NP of a bat influenza A-like virus, HL17NL10, in the context of a conventional IAV (SC35M). Replacement of conserved SC35M NP residues by those of HL17NL10 NP resulted in RNA packaging defective IAV. Surprisingly, substitution of these conserved SC35M amino acids with HL17NL10 NP residues led to IAV with altered packaging efficiencies for specific subsets of RNA segments. This suggests that NP harbours an amino acid code that dictates genome packaging into infectious virions. The nucleotide sequence of the eight genomic RNA segments of influenza A virus provides essential packaging signals, but how these sequences are recognized is unknown. Here, Moreira et al. identify conserved amino acids in the viral nucleoprotein that regulate packaging of RNA segments.
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