Proteomic analysis of SARS-CoV-2 particles unveils a key role of G3BP proteins in viral assembly
Émilie Murigneux, Laurent Softic, C. Aubé, Carmen Grandi, Delphine Judith, Johanna Bruce, Morgane Le Gall, François Guillonneau, Alain Schmitt, Vincent Parissi, Clarisse Berlioz‐Torrent, Laurent Meertens, Maike M. K. Hansen, Sarah Gallois‐Montbrun
Abstract
Considerable progress has been made in understanding the molecular host-virus battlefield during SARS-CoV-2 infection. Nevertheless, the assembly and egress of newly formed virions are less understood. To identify host proteins involved in viral morphogenesis, we characterize the proteome of SARS-CoV-2 virions produced from A549-ACE2 and Calu-3 cells, isolated via ultracentrifugation on sucrose cushion or by ACE-2 affinity capture. Bioinformatic analysis unveils 92 SARS-CoV-2 virion-associated host factors, providing a valuable resource to better understand the molecular environment of virion production. We reveal that G3BP1 and G3BP2 (G3BP1/2), two major stress granule nucleators, are embedded within virions and unexpectedly favor virion production. Furthermore, we show that G3BP1/2 participate in the formation of cytoplasmic membrane vesicles, that are likely virion assembly sites, consistent with a proviral role of G3BP1/2 in SARS-CoV-2 dissemination. Altogether, these findings provide new insights into host factors required for SARS-CoV-2 assembly with potential implications for future therapeutic targeting.