Lethal Viral Sepsis/Septic Shock in Getah Virus-Infected Ifnar1-/- Mice

Getah virus (GETV) is a mosquito-borne Old World alphavirus that has recently increased its geographic range, particularly in China. GETV causes rheumatic disease in horses, but in recent years its primary impact has been lethal infections in newborn piglets. Herein, we characterize a lethal Ifnar1-/- mouse model of GETV which recapitulates many of the features seen in piglets. These include lethality, high viremia, diarrhoea, and splenomegaly, with histopathological findings aligning with those seen in piglets and indicating severe, acute, multi-organ inflammatory immunopathology. RNA-Seq of spleens from GETV-infected Ifnar1-/- mice and subsequent bioinformatic analyses illustrated a cytokine storm response that included robust type I interferon signatures and a pattern of cytokine/chemokine signatures indicative of viral sepsis/septic shock. Ifnar1-/-mice thus offer a framework and a mouse model for understanding GETV disease in piglets. This model also suggests that viral sepsis/septic shock may be the cause of lethality in GETV-infected piglets.