Establishment of a mouse model for studying emerging Getah virus pathogenesis and vaccine efficacy

Getah virus (GETV), an emerging mosquito-borne alphavirus, poses a significant threat to livestock and potentially to humans, yet lacks approved antiviral therapies and vaccines. This absence underscores the critical need for a reliable small animal model to dissect GETV pathogenesis and evaluate interventions. Type I/II interferon receptor knockout (AG129) mice, a well established model for studying many viral infections, were evaluated for their GETV susceptibility. Here, we demonstrate that AG129 mice are highly susceptible to GETV infection. Unlike C57BL/6J and BALB/c mice, which exhibit only transient viremia, AG129 mice displayed 100% mortality, high viral loads in multiple organs, and severe neuropathology in the brain, spleen, and thymus, regardless of age or inoculation route. Importantly, the observed lesions in AG129 mice closely recapitulated pathological findings in experimentally infected horses report previously. Infected AG129 mice also mounted a pronounced systemic inflammatory response, evidenced by elevated circulating cytokines, and demonstrated complete protection upon vaccination with an inactivated GETV vaccine. Collectively, AG129 mice represent a highly susceptible and clinically relevant model for GETV, mirroring key features of natural disease in livestock. This model provides a critical platform for investigating GETV pathogenesis and evaluating novel vaccine and antiviral strategies.