TY - JOUR T1 - RetroCHMP3 Blocks Budding of Enveloped Viruses Without Blocking Cytokinesis JF - bioRxiv DO - 10.1101/2020.08.30.273656 SP - 2020.08.30.273656 AU - Lara Rheinemann AU - Diane Miller Downhour AU - Kate Bredbenner AU - Gaelle Mercenne AU - Kristen A. Davenport AU - Phuong Tieu Schmitt AU - Christina R. Necessary AU - John McCullough AU - Anthony P. Schmitt AU - Sanford M. Simon AU - Wesley I. Sundquist AU - Nels C. Elde Y1 - 2021/01/01 UR - http://biorxiv.org/content/early/2021/06/26/2020.08.30.273656.abstract N2 - Many enveloped viruses require the endosomal sorting complexes required for transport (ESCRT) pathway to exit infected cells. This highly conserved pathway mediates essential cellular membrane fission events, which restricts the acquisition of adaptive mutations to counteract viral co-option. Here, we describe duplicated and truncated copies of the ESCRT-III factor CHMP3 that block ESCRT-dependent virus budding and that arose independently in New World monkeys and mice. When expressed in human cells, these retroCHMP3 proteins potently inhibit release of retroviruses, paramyxoviruses, and filoviruses. Remarkably, retroCHMP3 proteins have evolved to reduce interactions with other ESCRT-III factors and to have little effect on cellular ESCRT processes, revealing routes for decoupling cellular ESCRT functions from viral exploitation. The repurposing of duplicated ESCRT-III proteins thus provides a mechanism to generate broad-spectrum viral budding inhibitors without blocking highly conserved essential cellular ESCRT functions.Competing Interest StatementThe authors have declared no competing interest. ER -