Figure 1.
ISGs restrict viral neuroinvasion. (A) ISGs in BMECs, which constitute the blood-brain barrier (BBB), are activated by virus and inflammation, leading to an IFN response and activation of transcription of antiviral ISGs, followed by activation of microglia and astrocytes to release ISGs. BMECs deliver the released ISGs to macrophages to enhance the antiviral response and restrict viral invasion. ① Neurotropic virus crosses the BBB through “Trojan horse” strategy. ② Virus infects endothelial cells across the BBB. ③ Virus enters the CNS by destroying the BBB. (B) The virus invades the CNS retrogradely through the olfactory pathway. The virus invades the olfactory sensory neurons through the olfactory epithelium and retrogrades upward into the olfactory bulb (OB). Virus at OB activates neurons, microglia, and macrophages, which produces IFN response and induces transcription of ISGs, leading to antiviral response. Long-distance signaling of IFN at the OB activates the transcription of ISGs in the brain. (C) IFNs produced by peripheral antiviral response enter the CNS and activate the transcription of ISGs in advance and induces transcription of ISGs, leading to antiviral response. Long-distance signaling of IFN at the OB activates the transcription of ISGs in the brain. (C) IFNs produced by peripheral antiviral response enter the CNS and activate the transcription of ISGs in advance. Created with BioRender.com.