RetroCHMP3 blocks budding of enveloped viruses without blocking cytokinesis

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

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

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 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 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.

Original languageEnglish (US)
Pages (from-to)5419-5431.e16
JournalCell
Volume184
Issue number21
DOIs
StatePublished - Oct 14 2021

All Science Journal Classification (ASJC) codes

  • General Biochemistry, Genetics and Molecular Biology

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