Project 466499

The SARS-CoV-2 nucleocapsid (N) protein is the most abundant protein expressed in virions and infected cells. It contains five RGG/RG motifs, preferential sites for protein arginine methyltransferases (PRMTs). Notably, R95 and R177 are sites of PRMT1 methylation previously identified by our lab (Cai et al., 2021) and are also predicted B and T cell epitopes. Autoantibodies have been reported in SARS-CoV-2-infected patients, and autoantibodies against arginine methylated residues have been isolated from patients with systemic lupus erythematosus (SLE). We propose that SARS-CoV-2-infected patients may develop antibodies against arginine methylated N protein that overlap with self-arginine methylated proteins and lead to autoimmune disease. To test this, we propose performing a series of ELISAs using differentially methylated peptides and plasma from SARS-CoV-2-infected patients. We also plan to perform a series of in vitro methylation assays and mass spectrometry to identify other SARS-CoV-2 proteins modified by PRMTs. These findings will have an impact on why certain patients post-SARS-CoV-2 infection develop persistent illnesses, especially autoimmune diseases. This project will also identify new post-translational modifications that may regulate SARS-CoV-2 biology.