MERS-CoV Nsp1 Impairs Cell Viability by Selectively Degrading the mRNAs of Ribosomal Protein Genes and Oxidative Phosphorylation Genes

Through screening, we found that Middle East respiratory syndrome coronavirus (MERS-CoV) non-structural protein 1 (nsp1) could inhibit cell viability, cell cycle, and cell migration through its endonuclease activity. Transcriptome sequencing revealed that MERS-CoV nsp1 specifically downregulated the mRNAs of ribosomal protein genes, oxidative phosphorylation protein genes, and antigen presentation genes, and upregulated the mRNAs of transcriptional regulatory genes. Nsp1 was found to exist in a novel ribonucleosome complex, and did not co-localize with mitochondria, lysosomes, P-bodies, or stress granules. The nsp1-located granules specifically contained mRNAs of ribosomal protein genes and oxidative phosphorylation genes, which may explain why MERS-CoV nsp1 selectively degraded these mRNAs in cells. Finally, MERS-CoV nsp1 transgenic mice showed significant loss of body weight and an increased sensitivity to poly(I:C)-induced inflammatory death. These findings demonstrate a new mechanism by which MERS-CoV impairs cell viability, which serves as a potential novel target for preventing MERS-CoV infection-induced pathological damage.