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Isolation, Transfection, and Culture of Primary Human Monocytes
Published on: December 16, 2019
Methadone Inhibits Viral Restriction Factors and Facilitates HIV Infection in Macrophages
Mei-Rong Wang1, Di-Di Wu1, Fan Luo1
1State Key Laboratory of Virology, Hubei Province Key Laboratory of Allergy and Immunology, School of Basic Medical Sciences, Institute of Medical Virology, Wuhan University, Wuhan, China.
Abstract:
Opioid abuse alters the functions of immune cells in both in vitro and in vivo systems, including macrophages. Here, we investigated the effects of methadone, a widely used opioid receptor agonist for treatment of opiate addiction, on the expression of intracellular viral restriction factors and HIV replication in primary human macrophages. We showed that methadone enhanced the HIV infectivity in primary human macrophages. Mechanistically, methadone treatment of macrophages reduced the expression of interferons (IFN-β and IFN-λ2) and the IFN-stimulated anti-HIV genes (APOBEC3F/G and MxB). In addition, methadone-treated macrophages showed lower levels of several anti-HIV microRNAs (miRNA-28, miR-125b, miR-150, and miR-155) compared to untreated cells. Exogenous IFN-β treatment restored the methadone-induced reduction in the expression of the above genes. These effects of methadone on HIV and the antiviral factors were antagonized by pretreatment of cells with naltrexone. These findings provide additional evidence to support further studies on the role of opiates, including methadone, in the immunopathogenesis of HIV disease.
Insights
Methadone increases HIV infectivity in human macrophages by suppressing key antiviral defenses, including interferons and microRNAs. Naltrexone can block these effects, suggesting a role for opiates in HIV immunopathogenesis.
Area of Science:
- Immunology
- Virology
- Pharmacology
Background:
- Opioid abuse impacts immune cell function, affecting macrophage activity.
- Methadone is a common treatment for opioid addiction, but its effects on HIV are not fully understood.
Purpose of the Study:
- To investigate how methadone affects intracellular antiviral factors and HIV replication in primary human macrophages.
- To elucidate the mechanisms by which methadone influences HIV infectivity.
Main Methods:
- Primary human macrophages were treated with methadone.
- Expression levels of interferons, IFN-stimulated genes, and anti-HIV microRNAs were measured.
- HIV infectivity was assessed in methadone-treated and untreated cells.
- Effects of exogenous IFN-β and naltrexone were evaluated.
Main Results:
- Methadone significantly enhanced HIV infectivity in human macrophages.
- Methadone treatment reduced the expression of interferons (IFN-β, IFN-λ2) and anti-HIV genes (APOBEC3F/G, MxB).
- Methadone decreased levels of anti-HIV microRNAs (miRNA-28, miR-125b, miR-150, miR-155).
- Exogenous IFN-β reversed methadone's suppressive effects, while naltrexone antagonized them.
Conclusions:
- Methadone compromises the innate antiviral defenses of macrophages, promoting HIV replication.
- These findings highlight the complex interplay between opioid use, immune function, and HIV pathogenesis.
- Further research into the immunomodulatory effects of methadone is warranted.
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