The uniqueness of the Brazilian Yellow Fever Virus. Are the vaccines less effective against it?

Abstract

The years 2016-2019 witnessed the expansion of Yellow Fever Virus (YFV) circulation area in Brazil. Deforestation and mutations in the nsp genes were presumed responsible for the reemergence of YFV in brazil. However, our data analysis involving 200 clinical isolates worldwide including vaccine strains showed two amino acids substitutions exclusively in the Brazilian strains at critical positions (V318A and I335M) in the ED III domain of E protein. Our molecular dynamics analysis involving reference and mutant structures suggests that the mutations significantly changed the conformational rearrangement and folding of the YFV-EDIII domain as revealed by RMSF, PCA, Porcupine plots and secondary structure analysis. Briefly, the regions 324-330, 339-346 and 347-359 had a higher fluctuation than the wild, while regions 313-318 and 379-384 had a lower fluctuation. As reported earlier that the residues E325 and E380 are part of vaccine epitopes and any mutations in these residues reduced the binding of vaccine generated mabs to the epitopes. Hence, it may be speculated from our porcupine plot data analysis that that the commercial YFV vaccines may not be fully effective against the Brazilian strains in particular owing to the fluctuations of these residues. However, future investigation is required to validate the observations.