Structural and biochemical analysis of the IBV nsp15 endoribonuclease reveals the necessity of peripheral site residues for activity

Infectious bronchitis virus (IBV), a Gammacoronavirus, induces respiratory illness and deforms eggshells in chickens, negatively affecting the poultry sector. Successful coronavirus replication hinges on evading the host's innate immune system. When coronaviruses replicate, double-stranded RNA (dsRNA) production triggers immune sensors that activate an antiviral state in infected cells.

To counteract this immune response, IBV employs nsp15, a nonstructural protein endoribonuclease, to degrade dsRNA. Researchers utilized cryo-electron microscopy and biochemistry to explore IBV nsp15's interactions with RNA. Although the overall structure and active site of IBV nsp15 resemble those of other coronaviruses, the double-stranded RNA interacts with unique peripheral residues not found in other coronaviruses.

These findings reveal the importance of these distinct residue positions in RNA cleavage, indicating that different coronavirus species may utilize unique mechanisms for RNA engagement. Additionally, the study demonstrates that IBV nsp15 prefers cleaving dsRNA over ssRNA and exhibits the ability to bind two dsRNAs simultaneously within hexamers.

This research emphasizes the necessity of studying various coronavirus species to uncover distinct viral enzyme characteristics.