Figure 4

Effect of INLAIs on the oligomeric state of IN. (A-B) IN-IN HTRF interaction: (A) IN-IN interaction activation dose–response curves. Data represent the means of three independent experiments done in duplicate with standard deviations shown as error bars. (B) Correlation between AC₅₀ of IN-IN interaction and EC₅₀ of ARV activity on MT4 cells infected with HxB2 HIV-1 (R² = 0.78). This study used 21 of the set of 51 compounds. AC₅₀ = concentration required to activate IN-IN interaction by 50% of the maximum effect. (C-F) Size exclusion chromatography of IN: Binding of INLAIs BI-D or Mut101, to IN NL4-3 wt (C-D) or IN NL4-3 A128T (E-F), promotes a shift toward higher IN oligomeric state, independently of LEDGF. Blue peaks: elution of IN wt and IN A128T in the absence of compound. Red peaks: elution of IN wt and IN A128T in the presence of BI-D (C, E) or Mut101 (D, F).The elution volume and identification of each peak (numbered 1 to 7) are indicated in supplementary table S2.