美国犹他大学医学院Nels C. Elde等研究人员合作发现，retroCHMP3阻断包膜病毒的出芽而不阻断细胞分裂。该项研究成果于2021年9月30日在线发表在《细胞》杂志上。

研究人员报道了运输所需的内体分拣复合物（ESCRT）-III因子CHMP3的重复和截断拷贝，它们阻断了ESCRT依赖的病毒出芽，并在猴和小鼠中独立出现。当在人类细胞中表达时，这些retroCHMP3蛋白能有效地抑制逆转录病毒、副黏液病毒和丝状病毒的释放。

值得注意的是，retroCHMP3蛋白在进化过程中减少了与其他ESCRT-III因子的相互作用，对细胞ESCRT过程的影响很小，从而揭示了将细胞ESCRT功能与病毒利用脱钩的途径。因此，ESCRT-III蛋白的再利用提供了一种机制，可在不阻断高度保守的基本细胞ESCRT功能的情况下产生广谱的病毒出芽抑制剂。

据了解，许多包膜病毒需要ESCRT途径来逃出被感染的细胞。这一高度保守的途径介导了基本的细胞膜分裂事件，这限制了获得适应性突变来对抗病毒的共存。

附：英文原文

Title: RetroCHMP3 blocks budding of enveloped viruses without blocking cytokinesis

Author: Lara Rheinemann, Diane Miller Downhour, Kate Bredbenner, Gaelle Mercenne, Kristen A. Davenport, Phuong Tieu Schmitt, Christina R. Necessary, John McCullough, Anthony P. Schmitt, Sanford M. Simon, Wesley I. Sundquist, Nels C. Elde

Issue&Volume: 2021-09-30

Abstract: Many enveloped viruses require the endosomal sorting complexes required for transport(ESCRT) pathway to exit infected cells. This highly conserved pathway mediates essentialcellular membrane fission events, which restricts the acquisition of adaptive mutationsto counteract viral co-option. Here, we describe duplicated and truncated copies ofthe ESCRT-III factor CHMP3 that block ESCRT-dependent virus budding and arose independentlyin New World monkeys and mice. When expressed in human cells, these retroCHMP3 proteinspotently inhibit release of retroviruses, paramyxoviruses, and filoviruses. Remarkably,retroCHMP3 proteins have evolved to reduce interactions with other ESCRT-III factorsand have little effect on cellular ESCRT processes, revealing routes for decouplingcellular ESCRT functions from viral exploitation. The repurposing of duplicated ESCRT-IIIproteins thus provides a mechanism to generate broad-spectrum viral budding inhibitorswithout blocking highly conserved essential cellular ESCRT functions.

DOI: 10.1016/j.cell.2021.09.008

Source: https://www.cell.com/cell/fulltext/S0092-8674(21)01055-2