Inhibition of HIV activation in latently infected cells by flavonoid compounds

J. W. Critchfield, S. T. Butera, T. M. Folks

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    139 Scopus citations

    Abstract

    Acute HIV-1 infection of H9 and C8166 cultures has been shown to be suppressed by certain flavonoids, and evidence for inhibition of HIV-1 protease, integrase, and reverse transcriptase by flavonoids also exists. The present aim was to determine whether flavonoids inhibit HIV-1 activation 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-α-treated OM- 10.1 cultures. The three compounds had favorable potencies against HIV activation in relation to their growth inhibitory effects (therapeutic index 5-10). Chrysin also inhibited HIV expression in response to PMA in OM-10.1 cells, in ACH-2 cells stimulated with either TNF-α or PMA, and in 8E5 cultures. Furthermore, return to vital latency in OM-10.1 cells previously exposed to TNF-α occurred over a shorter time interval when chrysin was added. The inhibition of HIV activation was not dependent on preincubation with flavonoids relative to TNF, and was characterized by a lack of HIV RNA accumulation by Northern analysis. Gel-shift experiments revealed that NF- κB activation after TNF-α treatment was not inhibited by these agents, suggesting that some other critical factor(s) needed for viral transcription was being affected. These findings indicate that flavonoids inhibit HIV-1 activation via a novel mechanism, and that these agents are potential candidates for therapeutic strategies aimed at maintaining a cellular state of HIV-1 latency.

    Original languageEnglish (US)
    Pages (from-to)39-46
    Number of pages8
    JournalAIDS Research and Human Retroviruses
    Volume12
    Issue number1
    DOIs
    StatePublished - 1996

    ASJC Scopus subject areas

    • Immunology
    • Virology
    • Infectious Diseases

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