FXR2 Promotes Autophagic Clearance of Sindbis Virus Capsid and Protects Against Viral Encephalitis

FXR2 promotes autophagic clearance of Sindbis virus capsid, and Fxr2-null mice show increased mortality and neuronal degeneration after neurotropic SINV challenge.

• Why it matters: Autophagy can protect neurons by removing viral components, but the host factors that recognize viral proteins and direct their clearance are not fully defined.
• What they did: Quantitative proteomics of host proteins associated with SINV capsid identified FXR2; co-immunoprecipitation and immunofluorescence showed FXR2 associates and colocalizes with capsid, and FXR2 loss reduced LC3 lipidation, autophagosome formation, and p62 degradation.
• The result: Reconstituting FXR2 in deficient cells restored autophagy and capsid clearance; FXR2 deficiency increased virus-induced cell death without significantly increasing viral replication, and in mice it caused greater neuronal damage and inflammation with comparable viral titers.