20 January 2024 | Emilie Murigneux, Laurent Softic, Corentin Aube, Carmen Grandi, Delphine Judith, Johanna Bruce, Morgane Le Gall, Francois Guillonneau, Alain Schmitt, Vincent Parissi, Clarisse Berlioz-Torrent, Laurent Meertens, Maike M. K. Hansen, Sarah Gallois-Montbrun
This study investigates the role of host proteins in the assembly and egress of SARS-CoV-2 virions. Proteomic analysis of virions isolated from A549-ACE2 and Calu-3 cells identified 356 host factors associated with SARS-CoV-2 virions, including a subset of stress granule proteins (SGPs) such as G3BP1 and G3BP2. G3BP1/2, which are major nucleators of SGs, were found to be embedded within virions and were shown to participate in the formation of cytoplasmic membrane vesicles that likely serve as sites for virion assembly. Knockdown of G3BP1/2 reduced the production of infectious virions, suggesting a proviral role for these proteins in SARS-CoV-2 replication. The study also revealed that G3BP1/2 interact with the viral structural proteins N, S, and M, and viral RNA, and accumulate in structures containing ERGIC-derived membranes, indicating their involvement in virion assembly and/or accumulation. These findings provide new insights into the host factors required for SARS-CoV-2 assembly and have potential implications for therapeutic targeting.This study investigates the role of host proteins in the assembly and egress of SARS-CoV-2 virions. Proteomic analysis of virions isolated from A549-ACE2 and Calu-3 cells identified 356 host factors associated with SARS-CoV-2 virions, including a subset of stress granule proteins (SGPs) such as G3BP1 and G3BP2. G3BP1/2, which are major nucleators of SGs, were found to be embedded within virions and were shown to participate in the formation of cytoplasmic membrane vesicles that likely serve as sites for virion assembly. Knockdown of G3BP1/2 reduced the production of infectious virions, suggesting a proviral role for these proteins in SARS-CoV-2 replication. The study also revealed that G3BP1/2 interact with the viral structural proteins N, S, and M, and viral RNA, and accumulate in structures containing ERGIC-derived membranes, indicating their involvement in virion assembly and/or accumulation. These findings provide new insights into the host factors required for SARS-CoV-2 assembly and have potential implications for therapeutic targeting.