TY - JOUR T1 - Vaccinia virus hijacks ESCRT-mediated multivesicular body formation for virus egress JF - Life Science Alliance JO - Life Sci. Alliance DO - 10.26508/lsa.202000910 VL - 4 IS - 8 SP - e202000910 AU - Moona Huttunen AU - Jerzy Samolej AU - Robert J Evans AU - Artur Yakimovich AU - Ian J White AU - Janos Kriston-Vizi AU - Juan Martin-Serrano AU - Wesley I Sundquist AU - Eva-Maria Frickel AU - Jason Mercer Y1 - 2021/08/01 UR - https://www.life-science-alliance.org/content/4/8/e202000910.abstract N2 - 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. ER -