In summary, while the described differences between nsp3-4-expressing and MERS-CoV-infected cells suggest that other viral components may modulate the process of DMV formation and would be required to form the full array of membrane structures observed during infection, our results establish that MERS-CoV nsp3 and nsp4 are sufficient to trigger all the membrane-remodeling steps required for inducing DMV formation, likely through the transformation of ER membranes into an RVN consisting of DMVs and modified ER. This evidence concerns the gene PRSS57 and infection.