Sulforaphane blocks HIV infection of macrophages (IRC4P.459)

Abstract

Abstract Despite highly active anti-retroviral treatment (HAART), HIV infection still claims millions of lives annually. HAART therapy is accompanied by high financial costs, the emergence of resistant viruses and short- and long-term side-effects. For this adjunctive therapeutic based on natural products should be considered to ameliorate complications due to HIV infection. Here we show for the first time that sulforaphane (SFN), a natural product produced in cruciferous vegetables blocks HIV infection in primary macrophages but not in primary T cells or several other cell types tested by mobilizing the transcription factor nuclear erythroid 2-related factor 2 (Nrf2). SFN blocked HIV infection in macrophages and macrophage-like cell lines by triggering a block before proviral integration. Furthermore we found that other compounds known to mobilize Nrf2 in macrophages also establish an intracellular state that counters HIV infection. Additionally we found that depleting Nrf2 boosts HIV infection in primary macrophage cultures. This led us to hypothesize that SFN and other compounds that trigger Nrf2 action, in macrophages, act through this protein to establish an intracellular antiviral state that counters HIV. We propose that SFN and other modulators of Nrf2 can be used to block HIV infection and therefore SFN could serve as an auxiliary therapeutic in ART experienced patients.