Interferon Regulatory Factor 7-mediated induction of interferon-α is required for survival from alphavirus encephalomyelitis

Abstract Alphaviruses are a group of arthropod-borne viruses that have the capacity to cause encephalomyelitis, which is inflammation brain and spinal cord due immune response viral infection, can result in fever, headache, neurologic disease such as cognitive impairment, seizures, ataxia, paralysis. Neurons primary target cells Sindbis virus (SINV), prototypic alphavirus; however, indispensable nature neurons, mechanisms clearance from central nervous system (CNS) during recovery cannot depend on immune-mediated killing infected neurons therefore specialized. We previously shown interferon (IFN) regulatory factor (IRF) 7, transcription important for amplification type I IFN (mainly IFNα), required survival infection with SINV. Mice deficient IRF7 succumb – despite local production IFNβ while wild (WT) mice recover. Treatment Irf7−/−mice IFNα rescues WT phenotype, suggesting IRF7-mediated induction subsequent downstream signaling SINV infection. Additionally, Ifnb−/−mice do not phenocopy Irf7−/−mice, further dispensable usage same receptor. Interestingly, similar titers implying protective effects independent restriction replication. These findings show subtype-specific differences protection by inform treatment options alphavirus-induced encephalomyelitis. works been funded U.S. National Institutes Health (R01 NS087539 T32 AI007417).