Fig. 3: Diverse HIV-1 factors induce microglial activation through distinct pathways involving in NLRP3 inflammasome and NF-κB signaling. | Translational Psychiatry

Fig. 3: Diverse HIV-1 factors induce microglial activation through distinct pathways involving in NLRP3 inflammasome and NF-κB signaling.

From: Neuroinflammation and NeuroHIV: understanding the role of HIV-1 related factors in microglial activation

Fig. 3: Diverse HIV-1 factors induce microglial activation through distinct pathways involving in NLRP3 inflammasome and NF-κB signaling.

a NLRP3 Inflammasome Activation: ① HIV-1 gp120 enhances Kv1.3 expression via C-X-C chemokine receptor type 4 (CXCR4) and p38-mitogen-activated protein kinase (p38-MAPK) signaling, leading to the activation of the NLRP3 inflammasome. ⑤ The viral protein Vpr directly activates the NLRP3 inflammasome. ⑥ HIV-1 ssRNA40 triggers NLRP3 inflammasome activation through toll-like receptor (TLR) 7/8-mediated mitochondrial damage. b NF-κB Pathway Activation: ② Binding of gp120 to CXCR4 activates the nuclear factor-kappa B (NF-κB) pathway, which then induces the transcription and expression of NLRP3 and pro-IL-1β. ③ HIV-1 gp120 also facilitates microglial activation through the purinergic 2×7 receptor (P2X7R)-mediated NF-κB signaling pathway. ④ Gp120 activate microglia by TLR 2-NF-κB signaling and by the direct binding of p62 and protein kinase C (PKC) through the IKK/NF-κB signaling pathway.

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