破坏埃博拉病毒 NPVP35 包涵体样结构可减少病毒感染。
Disruption of Ebola NPVP35 Inclusion Body-like Structures reduce Viral Infection.
机构信息
Department of Pathology and Immunology, Washington University School of Medicine in St. Louis, St. Louis, MO, USA.
Department of Chemistry, Washington University in St. Louis, St. Louis, MO, USA; Department of Medicine, Washington University School of Medicine in St. Louis, St. Louis, MO, USA.
出版信息
J Mol Biol. 2023 Oct 15;435(20):168241. doi: 10.1016/j.jmb.2023.168241. Epub 2023 Aug 19.
Viral inclusion bodies (IBs) are potential sites of viral replication and assembly. How viral IBs form remains poorly defined. Here we describe a combined biophysical and cellular approach to identify the components necessary for IB formation during Ebola virus (EBOV) infection. We find that the eNPVP35 complex containing Ebola nucleoprotein (eNP) and viral protein 35 (eVP35), the functional equivalents of nucleoprotein (N) and phosphoprotein (P) in non-segmented negative strand viruses (NNSVs), phase separates to form inclusion bodies. Phase separation of eNPVP35 is reversible and modulated by ionic strength. The multivalency of eVP35, and not eNP, is also critical for phase separation. Furthermore, overexpression of an eVP35 peptide disrupts eNPVP35 complex formation, leading to reduced frequency of IB formation and limited viral infection. Together, our results show that upon EBOV infection, the eNPVP35 complex forms the minimum unit to drive IB formation and viral replication.
病毒包含体（IBs）是病毒复制和组装的潜在场所。病毒 IBs 的形成方式仍未得到很好的定义。在这里，我们描述了一种结合生物物理和细胞的方法，以确定在埃博拉病毒（EBOV）感染过程中形成 IB 所需的成分。我们发现，含有埃博拉核蛋白（eNP）和病毒蛋白 35（eVP35）的 eNPVP35 复合物，是无分段负链病毒（NNSV）中核蛋白（N）和磷蛋白（P）的功能等价物，相分离形成包含体。eNPVP35 的相分离是可逆的，并受离子强度调节。eVP35 的多价性，而不是 eNP，对于相分离也是至关重要的。此外，eVP35 肽的过表达会破坏 eNPVP35 复合物的形成，导致 IB 形成频率降低和病毒感染受限。总之，我们的结果表明，在 EBOV 感染后，eNPVP35 复合物形成了驱动 IB 形成和病毒复制的最小单位。
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