INHIBITION OF HIV ACTIVATION IN LATENTLY INFECTED-CELLS BY FLAVONOID COMPOUNDS

Acute HIV-1 infection of H9 and C8166 cultures has been shown to be su ppressed by certain flavonoids, and evidence for inhibition of HIV-1 p rotease, integrase, and reverse transcriptase by flavonoids also exist s, The present aim was to determine whether flavonoids inhibit HIV-1 a ctivation in models of latent infection, By screening flavonoids from six different classes, three structurally related compounds (chrysin, acacetin, and apigenin) were identified that inhibited HIV expression in TNF-alpha-treated OM-10.1 cultures, The three compounds had favorab le potencies against HIV activation in relation to their growth inhibi tory effects (therapeutic index 5-10), Chrysin also inhibited HIV expr ession in response to PMA in OM-10.1 cells, in ACH-2 cells stimulated with either TNF-alpha or PMA, and in 8E5 cultures, Furthermore, return to viral latency in OM-10.1 cells previously exposed to TNF-alpha occ urred over a shorter time interval when chrysin was added, The inhibit ion of HIV activation was not dependent on preincubation with flavonoi ds relative to TNF, and was characterized by a lack of HIV RNA accumul ation by Northern analysis, Gel-shift experiments revealed that NF-kap pa B activation after TNF-alpha treatment was not inhibited by these a gents, suggesting that some other critical factor(s) needed for viral transcription was being affected, These findings indicate that flavono ids inhibit HIV-1 activation via a novel mechanism, and that these age nts are potential candidates for therapeutic strategies aimed at maint aining a cellular state of HIV-1 latency.