Vaccinia virus hijacks ESCRT-mediated multivesicular body formation for virus egress

Moona Huttunen, Jerzy Samolej, Robert J Evans, Artur Yakimovich, Ian J White, Janos Kriston-Vizi, Juan Martin-Serrano, Wesley I Sundquist, Eva-Maria Frickel, Jason Mercer

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Poxvirus egress is a complex process whereby cytoplasmic single membrane–bound virions are wrapped in a cell-derived double membrane. These triple-membrane particles, termed intracellular enveloped virions (IEVs), are released from infected cells by fusion. Whereas the wrapping double membrane is thought to be derived from virus-modified trans-Golgi or early endosomal cisternae, the cellular factors that regulate virus wrapping remain largely undefined. To identify cell factors required for this process the prototypic poxvirus, vaccinia virus (VACV), was subjected to an RNAi screen directed against cellular membrane-trafficking proteins. Focusing on the endosomal sorting complexes required for transport (ESCRT), we demonstrate that ESCRT-III and VPS4 are required for packaging of virus into multivesicular bodies (MVBs). EM-based characterization of MVB-IEVs showed that they account for half of IEV production indicating that MVBs are a second major source of VACV wrapping membrane. These data support a model whereby, in addition to cisternae-based wrapping, VACV hijacks ESCRT-mediated MVB formation to facilitate virus egress and spread.
Original languageEnglish
Article numbere202000910
JournalLife Science Alliance
Issue number8
Early online date18 Jun 2021
Publication statusPublished - Aug 2021


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