A Duplicated ESCRT-III Factor Blocks Enveloped Virus Budding Without Inhibiting Cellular ESCRT Functions
SummaryMany 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 and therefore has limited potential to acquire adaptive mutations to counteract this co-option by viruses. Here, we describe duplicated and truncated copies of the ESCRT-III factor CHMP3 that arose independently in New World monkeys and mice and that block ESCRT-dependent virus budding. When expressed in human cells, these retroCHMP3 proteins potently inhibit the release of retroviruses, paramyxoviruses and filoviruses. 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 exploitation by viruses. The repurposing of duplicated ESCRT-III proteins thus provides a mechanism to generate broad-spectrum viral budding inhibitors without disrupting highly conserved essential cellular ESCRT functions.