A conserved E1 stem motif functions as a virulence switch in the emerging Getah virus

and completely abrogates lethality in neonatal mice by restricting systemic dissemination. Stepwise mutagenesis further revealed that the four‑residue motif functions synergistically as a virulence switch: single deletions partially reduce pathogenicity, while the quadruple deletion confers full attenuation, limiting tissue tropism and histopathology. Although both wild‑type and mutant viruses crossed the placental barrier in pregnant mice, the mutant exhibited reduced vertical transmission and maternal tissue replication. Our findings identify a highly conserved E1 stem motif as a critical regulator of GETV virulence, offering a strategic target for developing attenuated vaccines against GETV and other alphaviruses.