Since the beginning of the SARS-CoV-2 epidemic, numerous studies have characterized the molecular interactions between the virus and the host cell that control viral replication. However, the late stages of assembly and production of new virions remain less well understood. During these late stages, newly synthesized viral proteins assemble in cells with the viral genome to form new virions that will be released from the cell surface. At this point, factors present in the cellular environment become trapped in these forming virions. Some of these factors are required for the assembly of these new infectious viral particles, while others hinder their production and infectivity.
To characterize the factors orchestrating the assembly of SARS-CoV-2 virions, Sarah Gallois-Montbrun's group, in the Host-Virus Interaction team, isolated SARS-CoV-2 virions produced by two different techniques from two infected lung cell lines. In collaboration with the proteomics and electron microscopy platforms at Institut Cochin (respectively Proteom'IC and PIME), these researchers identified, through mass spectrometry, all the viral and cellular proteins associated with the virions. Through bioinformatic analyses and literature data, 92 factors particularly enriched in the virions were identified. Among these factors, two proteins, G3BP1 and G3BP2, drew their attention. These proteins induce phase changes, leading to the formation of cytoplasmic granules called stress granules in response to cellular stresses such as viral infections. The authors reveal in this study that G3BP1 and G3BP2 proteins are present at virus assembly sites and interact within cells and virions with the viral nucleocapsid (N) protein, an essential protein in virus assembly. In the absence of G3BP1 and G3BP2, the N protein is less recruited to the membranes where viral particles assemble, viral assembly sites are less numerous, and consequently, virion production and dissemination are reduced.
In conclusion, these findings provide a better understanding of the molecular environment of SARS-CoV-2 assembly sites and reveal a new role for G3BP1 and G3BP2 proteins in the production of SARS-CoV-2 virions. This study opens up new perspectives for the development of therapeutic strategies targeting the late stages of SARS-CoV-2 replication.
Reference
Emilie Murigneux, Laurent Softic, Corentin 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 and Sarah Gallois-Montbrun. Proteomic analysis of SARS-CoV-2 particles unveils a key role of G3BP proteins in viral assembly. Nat Commun 15, 640 (2024). https://doi.org/10.1038/s41467-024-44958-0
