Hypothetic anti-HIV mechanism of TLR3 signaling of ECs. Stimulation of brain ECs with dsRNA activates TLR3 and/or RIG-I pathways, which facilitates phosphorylation and translocation of IRF3 and IRF7, initiating the transcription of IFN-β and IFN-λ in the ECs. When released from the ECs, IFN-β and IFN-λ bind to their receptors in macrophages and activate ISGF3, STAT3, and MAPK, inducing anti-HIV ISGs in macrophages. GAF, gamma-interferon activation factor; JAK1, Janus kinase 1; MAVS, mitochondrial antiviral-signaling protein; P, phosphorylation; TRIF, TIR-domain-containing adapter-inducing interferon-β; TYK2, Tyrosine kinase 2.