Limits...
Sulforaphane Inhibits HIV Infection of Macrophages through Nrf2.

Furuya AK, Sharifi HJ, Jellinger RM, Cristofano P, Shi B, de Noronha CM - PLoS Pathog. (2016)

Bottom Line: We further found that, like the type I interferon-induced cellular anti-viral proteins SAMHD1 and MX2, SFN treatment blocks infection after entry, but before formation of 2-LTR circles.Interestingly however, neither SAMHD1 nor MX2 were upregulated.This shows for the first time that Nrf2 action can potently block HIV infection and highlights a novel way to trigger this inhibition.

View Article: PubMed Central - PubMed

Affiliation: Center for Immunology and Microbial Disease, Albany Medical College, Albany, New York, United States of America.

ABSTRACT
Marburg virus, the Kaposi's sarcoma-associated herpesvirus (KSHV) and Dengue virus all activate, and benefit from, expression of the transcription regulator nuclear erythroid 2-related factor 2 (Nrf2). The impact of Nrf2 activation on human immunodeficiency virus (HIV) infection has not been tested. Sulforaphane (SFN), produced in cruciferous vegetables after mechanical damage, mobilizes Nrf2 to potently reprogram cellular gene expression. Here we show for the first time that SFN blocks HIV infection in primary macrophages but not in primary T cells. Similarly SFN blocks infection in PMA-differentiated promonocytic cell lines, but not in other cell lines tested. siRNA-mediated depletion of Nrf2 boosted HIV infectivity in primary macrophages and reduced the anti-viral effects of SFN treatment. This supports a model in which anti-viral activity is mediated through Nrf2 after it is mobilized by SFN. We further found that, like the type I interferon-induced cellular anti-viral proteins SAMHD1 and MX2, SFN treatment blocks infection after entry, but before formation of 2-LTR circles. Interestingly however, neither SAMHD1 nor MX2 were upregulated. This shows for the first time that Nrf2 action can potently block HIV infection and highlights a novel way to trigger this inhibition.

Show MeSH

Related in: MedlinePlus

SFN blocks HIV in primary macrophages but not primary T cells.(A), Primary T cells and (B), hMDMs were treated with media supplemented with vehicle only (DMSO) or with 10 μM, 20 μM or 30 μM SFN. Pretreatment of cultures with 5 μM of the reverse transcription inhibitor zidovudine (AZT) served as a positive control for viral inhibition. Twenty-four hours after treatment, cells were either mock infected or infected with VSV-G-pseudotyped HIV-1, encoding firefly luciferase in place of nef. Twenty-four hours after infection, the cells were harvested and luciferase activity was measured by photon emission. The bar graphs represent the data for replicate experiments (n = 3).
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4836681&req=5

ppat.1005581.g001: SFN blocks HIV in primary macrophages but not primary T cells.(A), Primary T cells and (B), hMDMs were treated with media supplemented with vehicle only (DMSO) or with 10 μM, 20 μM or 30 μM SFN. Pretreatment of cultures with 5 μM of the reverse transcription inhibitor zidovudine (AZT) served as a positive control for viral inhibition. Twenty-four hours after treatment, cells were either mock infected or infected with VSV-G-pseudotyped HIV-1, encoding firefly luciferase in place of nef. Twenty-four hours after infection, the cells were harvested and luciferase activity was measured by photon emission. The bar graphs represent the data for replicate experiments (n = 3).

Mentions: SFN, in various contexts, has been found to impair bacteria, fungi and even viruses including Influenza A, respiratory syncytial virus (RSV) and Epstein-Barr virus (EBV) [35–39]. The impact of SFN on HIV infection however has not been tested in primary immune cells. Here, primary T cells were mock-treated or treated with 10 μM, 20 μM or 30 μM SFN for 24 hours. AZT-treated cells (5 μM) served as positive controls for infection inhibition. Cultures were infected with identical aliquots of VSV-G pseudotyped env(‒) HIV-1 luciferase reporter virus and harvested the following day. Cell lysates were tested for luciferase activity to quantify transcription from proviral DNA. While AZT suppressed infection, SFN did not impact infection throughout the dosage range tested (Fig 1A).


Sulforaphane Inhibits HIV Infection of Macrophages through Nrf2.

Furuya AK, Sharifi HJ, Jellinger RM, Cristofano P, Shi B, de Noronha CM - PLoS Pathog. (2016)

SFN blocks HIV in primary macrophages but not primary T cells.(A), Primary T cells and (B), hMDMs were treated with media supplemented with vehicle only (DMSO) or with 10 μM, 20 μM or 30 μM SFN. Pretreatment of cultures with 5 μM of the reverse transcription inhibitor zidovudine (AZT) served as a positive control for viral inhibition. Twenty-four hours after treatment, cells were either mock infected or infected with VSV-G-pseudotyped HIV-1, encoding firefly luciferase in place of nef. Twenty-four hours after infection, the cells were harvested and luciferase activity was measured by photon emission. The bar graphs represent the data for replicate experiments (n = 3).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4836681&req=5

ppat.1005581.g001: SFN blocks HIV in primary macrophages but not primary T cells.(A), Primary T cells and (B), hMDMs were treated with media supplemented with vehicle only (DMSO) or with 10 μM, 20 μM or 30 μM SFN. Pretreatment of cultures with 5 μM of the reverse transcription inhibitor zidovudine (AZT) served as a positive control for viral inhibition. Twenty-four hours after treatment, cells were either mock infected or infected with VSV-G-pseudotyped HIV-1, encoding firefly luciferase in place of nef. Twenty-four hours after infection, the cells were harvested and luciferase activity was measured by photon emission. The bar graphs represent the data for replicate experiments (n = 3).
Mentions: SFN, in various contexts, has been found to impair bacteria, fungi and even viruses including Influenza A, respiratory syncytial virus (RSV) and Epstein-Barr virus (EBV) [35–39]. The impact of SFN on HIV infection however has not been tested in primary immune cells. Here, primary T cells were mock-treated or treated with 10 μM, 20 μM or 30 μM SFN for 24 hours. AZT-treated cells (5 μM) served as positive controls for infection inhibition. Cultures were infected with identical aliquots of VSV-G pseudotyped env(‒) HIV-1 luciferase reporter virus and harvested the following day. Cell lysates were tested for luciferase activity to quantify transcription from proviral DNA. While AZT suppressed infection, SFN did not impact infection throughout the dosage range tested (Fig 1A).

Bottom Line: We further found that, like the type I interferon-induced cellular anti-viral proteins SAMHD1 and MX2, SFN treatment blocks infection after entry, but before formation of 2-LTR circles.Interestingly however, neither SAMHD1 nor MX2 were upregulated.This shows for the first time that Nrf2 action can potently block HIV infection and highlights a novel way to trigger this inhibition.

View Article: PubMed Central - PubMed

Affiliation: Center for Immunology and Microbial Disease, Albany Medical College, Albany, New York, United States of America.

ABSTRACT
Marburg virus, the Kaposi's sarcoma-associated herpesvirus (KSHV) and Dengue virus all activate, and benefit from, expression of the transcription regulator nuclear erythroid 2-related factor 2 (Nrf2). The impact of Nrf2 activation on human immunodeficiency virus (HIV) infection has not been tested. Sulforaphane (SFN), produced in cruciferous vegetables after mechanical damage, mobilizes Nrf2 to potently reprogram cellular gene expression. Here we show for the first time that SFN blocks HIV infection in primary macrophages but not in primary T cells. Similarly SFN blocks infection in PMA-differentiated promonocytic cell lines, but not in other cell lines tested. siRNA-mediated depletion of Nrf2 boosted HIV infectivity in primary macrophages and reduced the anti-viral effects of SFN treatment. This supports a model in which anti-viral activity is mediated through Nrf2 after it is mobilized by SFN. We further found that, like the type I interferon-induced cellular anti-viral proteins SAMHD1 and MX2, SFN treatment blocks infection after entry, but before formation of 2-LTR circles. Interestingly however, neither SAMHD1 nor MX2 were upregulated. This shows for the first time that Nrf2 action can potently block HIV infection and highlights a novel way to trigger this inhibition.

Show MeSH
Related in: MedlinePlus