Importantly, EV-A71 virus infection induced the phosphorylation and cytoplasmic relocalization of SR proteins, which co-localized with vRNA and co-sedimented with components of the translation apparatus, Functional analyses demonstrated that the knockdown of specific SR proteins, including SRSF4, SRSF5, and SRSF6, significantly attenuated viral replication. Here, SRSF6 is linked to epidermodysplasia verruciformis.