基础科学部和计算生物学项目Jesse D. Bloom研究组取得一项新突破。他们揭示了尼帕病毒受体结合蛋白的功能和抗原景观。相关论文于2025年3月24日发表在《细胞》杂志上。

小组进行了深度突变扫描，以测量RBP的所有氨基酸突变如何影响细胞进入、受体结合和从中和抗体中逃逸。该团队确定了RBP的功能受限区域，包括参与寡聚化的位点，以及差异调节RBP与其两种ephrin受体结合的突变。研究人员绘制了六种抗RBP抗体的逃逸突变图，发现天然尼帕病毒株中很少存在抗原突变。他们的发现为RBP的功能和抗原进化潜力提供了见解，可以为抗体疗法和疫苗的开发提供信息。

研究人员表示，尼帕病毒经常溢出到人类身上，引发致命感染。病毒受体结合蛋白（RBP或G）附着在宿主受体上，是中和抗体的主要靶点。

附：英文原文

Title: Functional and antigenic landscape of the Nipah virus receptor-binding protein

Author: Brendan B. Larsen, Teagan McMahon, Jack T. Brown, Zhaoqian Wang, Caelan E. Radford, James E. Crowe, David Veesler, Jesse D. Bloom

Issue&Volume: 2025-03-24

Abstract: Nipah virus recurrently spills over to humans, causing fatal infections. The viral receptor-binding protein (RBP or G) attaches to host receptors and is a major target of neutralizing antibodies. Here, we use deep mutational scanning to measure how all amino-acid mutations to the RBP affect cell entry, receptor binding, and escape from neutralizing antibodies. We identify functionally constrained regions of the RBP, including sites involved in oligomerization, along with mutations that differentially modulate RBP binding to its two ephrin receptors. We map escape mutations for six anti-RBP antibodies and find that few antigenic mutations are present in natural Nipah strains. Our findings offer insights into the potential for functional and antigenic evolution of the RBP that can inform the development of antibody therapies and vaccines.

DOI: 10.1016/j.cell.2025.02.030

Source: https://www.cell.com/cell/abstract/S0092-8674(25)00257-0