The PRV pUL37 R2 region is essential for virulence and can be mutated without causing misfolding of the surrounding protein structure.

(A) Kaplan–Meier presentation of mouse survival following intranasal instillation of wild-type PRV (WT) or PRV carrying mutations in the R1, R2, or R3 regions of the pUL37 tegument protein (n = 5 animals for each virus). All viruses encode a mCherry tag fused to the pUL25 capsid protein as previously described [30,47]. (B) The crystal structure of the N-terminal half of the PRV pUL37 R2 mutant (R2; lilac), determined in this work, was overlaid onto the previously determined wild-type structure (WT; beige) [47] with rmsd 0.5538 Å over 479 aligned residues as determined in Coot [93]. A close-up view of R2 is shown to the right with the side chains of the five targeted amino acids indicated for wild type and the mutant.