Cell
Volume 184, Issue 21, 14 October 2021, Pages 5419-5431.e16
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Article
RetroCHMP3 blocks budding of enveloped viruses without blocking cytokinesis

https://doi.org/10.1016/j.cell.2021.09.008Get rights and content
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Highlights

  • Truncated retrocopies of CHMP3 arose independently in New World monkeys and mice

  • RetroCHMP3 proteins broadly inhibit budding of ESCRT-dependent viruses

  • RetroCHMP3 proteins evolved to lose cytotoxicity associated with ESCRT inhibition

  • Delays in ESCRT function inhibit virus budding but spare critical host pathways

Summary

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.

Keywords

ESCRT pathway
HIV-1
virus budding
retrocopy
antiviral protein

Data and code availability

Sequencing data of CHMP3 retrocopies is provided in Table S1.

This study did not generate any new code.

Any additional information required to reanalyze the data reported in this paper is available from the lead contact upon request.

Cited by (0)

5

These authors contributed equally

6

Lead contact