Recovered DENV4/2 ED chimeras display ED epitopes of DENV2. The ED regions are colored in red, yellow, and blue for EDI, EDII, and EDIII, respectively. (A) Alignment of all differing amino acid residues on the surface ED between DENV4 and DENV2. Residues designed to be DENV2 are colored pink, while residues kept as DENV4 are white. This includes the additional DENV2 to DENV4 changes made for viral stability (DENV4/2-EDI M278L, S307K), and any residues within the ED that were kept DENV4 (DENV4/2-EDI Q36; DENV4/2-EDII I46, E49). Mutations that arose during passaging and then introduced into the molecular clone and rederived (DENV4/2-EDI H230N, K284R, K323R; DENV4/2-EDII N276Y and N366S) are hatched; DENV2 residues are in pink, and residues that are not shared by DENV4 and DENV2 are in gray. (B) Three monomers of each DENV4/2 ED chimera with changed residue backbones highlighted (PDB 3J27).