Methadone Inhibits Viral Restriction Factors and Facilitates HIV Infection in Macrophages

Mei Rong Wang, Di Di Wu, Fan Luo, Chao Jie Zhong, Xin Wang, Ni Zhu, Ying Jun Wu, Hai Tao Hu, Yong Feng, Xu Wang, Hai Rong Xiong, Wei Hou

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article number1253
JournalFrontiers in immunology
Volume11
DOIs
StatePublished - Jul 3 2020

Keywords

  • HIV
  • innate immunity
  • interferons
  • miRNAs
  • opioids

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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  • Cite this

    Wang, M. R., Wu, D. D., Luo, F., Zhong, C. J., Wang, X., Zhu, N., Wu, Y. J., Hu, H. T., Feng, Y., Wang, X., Xiong, H. R., & Hou, W. (2020). Methadone Inhibits Viral Restriction Factors and Facilitates HIV Infection in Macrophages. Frontiers in immunology, 11, [1253]. https://doi.org/10.3389/fimmu.2020.01253