Chenavier Florian, Zarkadas Eleftherios, Freslon Lily-Lorette, Stelfox Alice J, Schoehn Guy, Ruigrok Rob W H, Ballandras-Colas Allison, Crépin Thibaut
Univ. Grenoble Alpes, CNRS, CEA, IBS, 71 avenue des Martyrs, F-38000 Grenoble, France.
Univ. Grenoble Alpes, CNRS, CEA, EMBL, ISBG, 71 avenue des Martyrs, F-38000 Grenoble, France.
Nucleic Acids Res. 2025 Jan 24;53(3). doi: 10.1093/nar/gkae1211.
Influenza A viruses are responsible for human seasonal epidemics and severe animal pandemics with a risk of zoonotic transmission to humans. The viral segmented RNA genome is encapsidated by nucleoproteins (NP) and attached to the heterotrimeric polymerase, forming the viral ribonucleoproteins (vRNPs). Flexible helical vRNPs are central for viral transcription and replication. In this study, we present an advanced biological tool, the antiparallel helical RNP-like complex, assembled from recombinant N-terminally truncated NP and short synthetic RNA. The 3.0 Å cryo-electron microscopy structure details for the first time the whole RNA pathway across NP as well as NP-NP interactions that drive the antiparallel helical assembly accommodating major and minor grooves. Our findings show that the surface of the protein can harbour several conformations of the RNA, confirming that the number of nucleobases that binds to NP is not fixed, but ranges probably between 20 and 24. Taking all together, our data provide details to further understand the genome encapsidation and explain the inherent flexibility of influenza A virus vRNPs.
甲型流感病毒引发人类季节性流行疾病以及严重的动物大流行,并存在向人类进行人畜共患病传播的风险。病毒的分段RNA基因组由核蛋白(NP)包裹,并与异源三聚体聚合酶相连,形成病毒核糖核蛋白(vRNP)。灵活的螺旋状vRNP对于病毒转录和复制至关重要。在本研究中,我们展示了一种先进的生物学工具,即由重组N端截短的NP和短合成RNA组装而成的反平行螺旋RNP样复合物。3.0 Å的冷冻电子显微镜结构首次详细揭示了整个RNA穿过NP的途径以及驱动反平行螺旋组装以容纳大沟和小沟的NP-NP相互作用。我们的研究结果表明,蛋白质表面可容纳RNA的多种构象,证实与NP结合的核碱基数量并非固定不变,而是可能在20至24个之间。综上所述,我们的数据为进一步理解基因组包裹提供了详细信息,并解释了甲型流感病毒vRNP固有的灵活性。