Fig. 6 | Signal Transduction and Targeted Therapy

Fig. 6

From: Retinol Binding Protein 4 reactivates latent HIV-1 by triggering canonical NF-κB, JAK/STAT5 and JNK signalling

Fig. 6

Reactivation of latent HIV-1 in PBMCs from PLWH under cART. a Correlation between the number of total, defective and intact proviruses and RBP4 plasma levels in the corresponding PLWH using the Spearman correlation test. b Percentage of CD4+ cells of PBMCs from 7 PLWH under cART. c Percentage of intact and defective proviruses in CD4+ cells from cART-suppressed study participants, measured through IPDA. d Percent PBMC viability relative to IgG control after 72 h treatment with LRAs. Detection of Gag-p24 HIV-1 protein in cART-suppressed PBMC cell pellets (e) and culture supernatants (f) after 72 h treatment with LRAs as measured by SIMOA. p values are shown as measured by the Wilcoxon Signed-Rank test. g Proposed model of holo-RBP4-mediated reactivation of latent HIV-1. RBP4 activates latent HIV in responsive cells through an unknown receptor, independent of TLR4 and STRA6, which are absent or similarly expressed in both responsive and non-responsive cells. Inhibition and gene knockout studies implicate the canonical NF-κB, JNK, and STAT pathways in HIV reactivation. The coordinated engagement of these pathways leads to efficient reactivation of latent HIV. In addition, holo-RBP4 selectively induces a limited set of host genes, including the non-canonical NF-κB pathway in responsive cells, suggesting a distinct transcriptional signature associated with reactivation. The image has been generated using CorelDraw 2021.5

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