European Molecular Biology Laboratory, Grenoble, Cedex 9, France.
Institut Pasteur, Université Paris Cité, CNRS UMR3569, RNA Biology of Influenza Virus, Paris, France.
Nat Commun. 2024 Aug 19;15(1):6910. doi: 10.1038/s41467-024-51007-3.
Replication of influenza viral RNA depends on at least two viral polymerases, a parental replicase and an encapsidase, and cellular factor ANP32. ANP32 comprises an LRR domain and a long C-terminal low complexity acidic region (LCAR). Here we present evidence suggesting that ANP32 is recruited to the replication complex as an electrostatic chaperone that stabilises the encapsidase moiety within apo-polymerase symmetric dimers that are distinct for influenza A and B polymerases. The ANP32 bound encapsidase, then forms the asymmetric replication complex with the replicase, which is embedded in a parental ribonucleoprotein particle (RNP). Cryo-EM structures reveal the architecture of the influenza A and B replication complexes and the likely trajectory of the nascent RNA product into the encapsidase. The cryo-EM map of the FluB replication complex shows extra density attributable to the ANP32 LCAR wrapping around and stabilising the apo-encapsidase conformation. These structures give new insight into the various mutations that adapt avian strain polymerases to use the distinct ANP32 in mammalian cells.
流感病毒 RNA 的复制至少依赖两种病毒聚合酶，即亲代复制酶和包膜酶，以及细胞因子 ANP32。ANP32 包含一个 LRR 结构域和一个长的 C 端低复杂度酸性区域（LCAR）。本研究提供了证据表明，ANP32 作为一种静电伴侣被招募到复制复合物中，稳定包膜酶在 apo-聚合酶对称二聚体中的结构，而这种二聚体在流感 A 和 B 聚合酶中是不同的。结合包膜酶的 ANP32，然后与嵌入亲代核糖核蛋白颗粒（RNP）中的复制酶形成不对称复制复合物。冷冻电镜结构揭示了流感 A 和 B 复制复合物的结构以及新生 RNA 产物进入包膜酶的可能轨迹。FluB 复制复合物的冷冻电镜图谱显示了额外的密度归因于 ANP32 LCAR 的缠绕和稳定 apo-包膜酶构象。这些结构为适应禽类聚合酶在哺乳动物细胞中使用独特的 ANP32 的各种突变提供了新的见解。
