Figure 8

Model depicting the suggested signaling pathway modulated by CSs to inhibit HIV-1 gene expression. Although all CSs tested induce intracellular Ca²⁺ flux (left, gray) as well as activation of PLC-IP₃R-Ca²⁺, PI3K-AKT, and JNK/p38 MAPK signaling via the NKA signalosome (right, gray), this study supports the hypothesis that CSs suppress HIV-1 gene expression in part through the MEK1/2-ERK1/2 signaling pathway (black), in a manner which is independent of NCX-mediated Ca²⁺ influx responsible for potential Ca²⁺ overload of the sarco-/endoplasmic reticulum (SR/ER) and triggering of toxicity/arrhythmias in patients.