Defining the Impact of Getah Virus Envelope Protein Glycosylation Site Mutations on Viral Replication, Host Adaptation, Virulence, and Immune Evasion

Getah virus (GETV) is an emerging mosquito-borne alphavirus that causes significant animal outbreaks. Epidemic strains possess a unique N-glycosylation site (E2-N262) absent in historical lineages. The functional mechanisms of this site and conserved glycosylation structures in balancing viral replication, transmission, virulence, and immune evasion remained unclear. This study systematically investigated the impact of site-specific N-glycosylation on GETV fitness by characterizing seven glycosylation-deficient mutants. The findings reveal that these glycans are not merely structural modifications but critical determinants fine-tuning viral replication, host adaptation, virulence, and immune evasion, with evolutionary pressure favoring their retention to optimize epidemic fitness.