Figure 5

Functional assessment of variants affecting the TLR and NOD2 pathways, fibronectin plasma levels, and HIV replication upstream integration. (a,b) Patients with variants affecting the TLR sensing pathways (IRAK2 and TAB2 variants) and their a priori matched controls were stimulated with the TLR7/8 ligand Resiquimod (R848) (1 µg/mL) for 6 hrs followed by IL-6 qPCR. (c,d) Patients with variants affecting the NOD2 sensing pathways (NOD2 and TAB2 variants) and their a priori matched controls were stimulated with the NOD2 agonist muramyl dipeptide (MDP) (1 µg/mL) for 6 hrs followed by IL-8 qPCR. Means of triplicates with standard derivation are shown. (e) Measurements of plasma fibronectin levels in patients with variants in FN1 encoding fibronectin and in age- and gender-matched controls. Means are shown with each dot representing mean values from technical duplicates based on ELISA. Dotted line represents detection limit. (f) Integrated HIV DNA after infection with the HIV strain HXB2 at MOI 0.1 with endogenous levels of integrated HIV DNA subtracted. Integrated HIV DNA was measured in LTNPs harbouring variants potentially affecting HIV inward trafficking and integration (PIK3C2B, FRK, MAP1A, PIK3R5, FGD6, FN1, PIK3R6, and DDOST) and in age- and gender-matched controls. Error bars represent min and max values from technical replicates. Non-controller on ART (NCART); long-term non-progressor (LTNP); elite controller (EC); untreated (UT).