Interaction between host G3BP and viral nucleocapsid protein regulates SARS-CoV-2 replication

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.06.29.546885v1?rss=1 Authors: Yang, Z., Johnson, B. A., Meliopoulos, V. A., Ju, X., Zhang, P., Hughes, M. P., Wu, J., Koreski, K. P., Chang, T.-C., Wu, G., Hixon, J., Duffner, J., Wong, K., Lemieux, R., Lokugamage, K. G., Alvardo, R. E., Crocquet-Valdes, P. A., Walker, D. H., Plante, K. S., Plante, J. A., Weaver, S. C., Kim, H. J., Meyers, R., Schultz-Cherry, S., Ding, Q., Menachery, V. D., Taylor, J. P. Abstract: G3BP1/2 are paralogous proteins that promote stress granule formation in response to cellular stresses, including viral infection. G3BP1/2 are prominent interactors of the nucleocapsid (N) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the functional consequences of the G3BP1-N interaction in the context of viral infection remain unclear. Here we used structural and biochemical analyses to define the residues required for G3BP1-N interaction, followed by structure-guided mutagenesis of G3BP1 and N to selectively and reciprocally disrupt their interaction. We found that mutation of F17 within the N protein led to selective loss of interaction with G3BP1 and consequent failure of the N protein to disrupt stress granule assembly. Introduction of SARS-CoV-2 bearing an F17A mutation resulted in a significant decrease in viral replication and pathogenesis in vivo, indicating that the G3BP1-N interaction promotes infection by suppressing the ability of G3BP1 to form stress granules. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC