Alcohol Enhances HIV Infection of Cord Blood Monocyte-Derived Macrophages

Mastrogiannis, Dimitrios; Wang, Xu; Dai, Min; Li, Jieliang; Wang, Yizhong; Zhou, Yu; Sakarcan, Selin; Peña, Juliet C.; Ho, Wen‐Zhe

doi:10.2174/1570162x12666140721124923

Cited by 6 publications

(8 citation statements)

References 62 publications

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“…Our results show in vitro alcohol treatment of MDDC increased p24 secretion ( Figure 2A ), intracellular p24 levels ( Figures 3C,D and 4 ), percentage of cells expressing p24, and LTR ( Figure 5A ). Our findings are in accordance with previous reports showing alcohol enhances HIV-1 infection of human monocyte-derived cells; however, those reports were performed in cord blood monocyte-derived macrophages ( Mastrogiannis et al, 2014 ) and in blood monocyte-derived macrophages ( Wang et al, 2002 ). Furthermore, alcohol ingestion has been shown to increase HIV-1 replication in human PBMC, which may be due to alcohol-induced functional impairment of various subsets of lymphocytes in the peripheral blood ( Bagasra et al, 1993 ).…”

Section: Discussionsupporting

confidence: 93%

Alcohol and Cannabinoids Differentially Affect HIV Infection and Function of Human Monocyte-Derived Dendritic Cells (MDDC)

et al. 2015

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During human immunodeficiency virus (HIV) infection, alcohol has been known to induce inflammation while cannabinoids have been shown to have an anti-inflammatory role. For instance cannabinoids have been shown to reduce susceptibility to HIV-1 infection and attenuate HIV replication in macrophages. Recently, we demonstrated that alcohol induces cannabinoid receptors and regulates cytokine production by monocyte-derived dendritic cells (MDDC). However, the ability of alcohol and cannabinoids to alter MDDC function during HIV infection has not been clearly elucidated yet. In order to study the potential impact of alcohol and cannabinoids on differentiated MDDC infected with HIV, monocytes were cultured for 7 days with GM-CSF and IL-4, differentiated MDDC were infected with HIV-1Ba-L and treated with EtOH (0.1 and 0.2%), THC (5 and 10 μM), or JWH-015 (5 and 10 μM) for 4–7 days. HIV infection of MDDC was confirmed by p24 and Long Terminal Repeats (LTR) estimation. MDDC endocytosis assay and cytokine array profiles were measured to investigate the effects of HIV and substances of abuse on MDDC function. Our results show the HIV + EtOH treated MDDC had the highest levels of p24 production and expression when compared with the HIV positive controls and the cannabinoid treated cells. Although both cannabinoids, THC and JWH-015 had lower levels of p24 production and expression, the HIV + JWH-015 treated MDDC had the lowest levels of p24 when compared to the HIV + THC treated cells. In addition, MDDC endocytic function and cytokine production were also differentially altered after alcohol and cannabinoid treatments. Our results show a differential effect of alcohol and cannabinoids, which may provide insights into the divergent inflammatory role of alcohol and cannabinoids to modulate MDDC function in the context of HIV infection.

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Section: Discussionsupporting

confidence: 93%

Alcohol and Cannabinoids Differentially Affect HIV Infection and Function of Human Monocyte-Derived Dendritic Cells (MDDC)

et al. 2015

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“…Ethanol (20 mM) treatment alone showed a 20.6% increase in HIV replication compared to control (t(6) = 5.9, p = 0.001, student t test, Fig. 4), which is in line with the previous studies (21,22). Cells that were exposed to DRV alone or along with RTV exhibited approximately a 60% decrease in HIV replication ( p = 0.05 compared to control).…”

Section: Resultssupporting

confidence: 91%

Influence of Ethanol on Darunavir Hepatic Clearance and Intracellular PK/PD in HIV-Infected Monocytes, and CYP3A4-Darunavir Interactions Using Inhibition and in Silico Binding Studies

et al. 2017

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Purpose Although the prevalence of alcohol consumption is higher in HIV+ people than general public, limited information is available on how alcohol affects the metabolism and bioavailability of darunavir (DRV). Methods DRV was quantified by using LC-MS/MS method. All in vitro experiments were performed using human liver microsomes and HIV-infected monocytic cells. CYP3A4 and DRV/ Ritonavir (RTV) docking was performed using GOLD suite 5.8. Results Ethanol (20 mM) significantly decreased apparent half-life and increased degradation rate constant of RTV-boosted DRV but not for DRV alone. Similarly, ethanol exposure increased hepatic intrinsic clearance for RTV-boosted DRV with no significant influence on DRV alone. Ethanol showed a limited influence on intracellular total DRV exposure in the presence of RTV without altering maximum concentration (Cmax) values in HIV-infected monocytic cells. Ethanol alone elevated HIV replication but this effect was nullified with the addition of DRV or DRV + RTV. Additionally, inhibitory potency of DRV was significantly reduced in the presence of ethanol. Our docking results projected that ethanol increases the average distance between DRV and CYP3A4 heme, and alter the orientation of DRV-CYP3A4 binding. Conclusions Collectively these findings suggest that DRV metabolism is primarily influenced by ethanol in the liver, but has minor effect in HIV-residing monocytes.

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“…Our findings that ethanol causes an increase in HIV replication is in agreement with previously reported observations[ 35 – 37 ]. EVG or COBI-boosted EVG displayed a significant viricidal activity.…”

Section: Discussionsupporting

confidence: 94%

Alterations in cellular pharmacokinetics and pharmacodynamics of elvitegravir in response to ethanol exposure in HIV-1 infected monocytic (U1) cells

et al. 2017

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Ethanol consumption is negatively associated with antiretroviral therapy (ART) adherence and general health in HIV positive individuals. Previously, we demonstrated ethanol-mediated alterations to metabolism of elvitegravir (EVG) in human liver microsomes. In the current study, we investigated ethanol influence on the pharmacokinetic and pharmacodynamic interactions of EVG in HIV infected monocytic (U1) cells. U1 cells were treated with 5 μM EVG, 2 μM Cobicistat (COBI), a booster drug, and 20 mM ethanol for up to 24 hours. EVG, HIV p24 levels, alterations in cytochrome P450 (CYP) 3A4, MRP1, and MDR1 protein expressions were measured. Presence of ethanol demonstrated a significant effect on the total exposures of both EVG and EVG in combination with COBI. Ethanol also increased the HIV replication despite the presence of drugs and this elevated HIV replication was reduced in the presence of MRP1 and MDR1 inhibitors. Consequently, a slight increase in EVG concentration was observed in the presence of MRP1 inhibitor but not with MDR1 inhibitor. Furthermore, CYP3A4, MRP1 and MDR1 protein levels were significantly induced in treatment groups which included ethanol compared to those with no treatment. In summary, these findings suggest that Ethanol reduces intra cellular EVG exposure by modifying drug metabolism and transporter protein expression. This study provides valuable evidence for further investigation of ethanol effects on the intracellular concentration of EVG in ex vivo or in vivo studies.

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Alcohol Enhances HIV Infection of Cord Blood Monocyte-Derived Macrophages

Cited by 6 publications

References 62 publications

Alcohol and Cannabinoids Differentially Affect HIV Infection and Function of Human Monocyte-Derived Dendritic Cells (MDDC)

Alcohol and Cannabinoids Differentially Affect HIV Infection and Function of Human Monocyte-Derived Dendritic Cells (MDDC)

Influence of Ethanol on Darunavir Hepatic Clearance and Intracellular PK/PD in HIV-Infected Monocytes, and CYP3A4-Darunavir Interactions Using Inhibition and in Silico Binding Studies

Alterations in cellular pharmacokinetics and pharmacodynamics of elvitegravir in response to ethanol exposure in HIV-1 infected monocytic (U1) cells

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