MERS coronavirus nsp1 participates in an efficient propagation through a specific interaction with viral RNA

- MERS-CoV nsp1 interacts with Stem-loop 1 in 5′ UTR of viral RNA.
- Arginine at position 13 of MERS-CoV nsp1 is critical for viral RNA recognition.
- Nsp1-mediated Viral RNA recognition is important for efficient viral propagation.
- Functional amino acids of nsp1 differ between SARS-CoV and MERS-CoV.

MERS-CoV is the only lethal human CoV still endemic in the Arabian Peninsula and neither vaccine nor therapeutics against MERS-CoV infection is available. The nsp1 of CoV is thought to be a major virulence factor because it suppresses protein synthesis through the degradation of host mRNA. In contrast, viral RNA circumvents the nsp1-mediated translational shutoff for an efficient propagation. In this study, we identified amino acid residue in MERS-CoV nsp1 that differ from those of SARS-CoV nsp1, and that appear to be crucial for circumventing the translational shutoff. In addition, reverse genetics analysis suggested the presence of a cis-acting element at the 5′-terminus of the nsp1-coding region, which contributes to the specific recognition of viral RNA that is required for an efficient viral replication. Our results suggest the CoVs share a common mechanism for circumventing the nsp1-mediated translational shutoff.