Methadone Inhibits Viral Restriction Factors and Facilitates HIV Infection in Macrophages
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...
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doaj-cdc7266a6756478ab207d635c19410912020-11-25T03:01:48ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-07-011110.3389/fimmu.2020.01253532005Methadone Inhibits Viral Restriction Factors and Facilitates HIV Infection in MacrophagesMei-Rong Wang0Di-Di Wu1Fan Luo2Chao-Jie Zhong3Xin Wang4Ni Zhu5Ying-Jun Wu6Hai-Tao Hu7Yong Feng8Xu Wang9Hai-Rong Xiong10Wei Hou11Wei Hou12State Key Laboratory of Virology, Hubei Province Key Laboratory of Allergy and Immunology, School of Basic Medical Sciences, Institute of Medical Virology, Wuhan University, Wuhan, ChinaState Key Laboratory of Virology, Hubei Province Key Laboratory of Allergy and Immunology, School of Basic Medical Sciences, Institute of Medical Virology, Wuhan University, Wuhan, ChinaState Key Laboratory of Virology, Hubei Province Key Laboratory of Allergy and Immunology, School of Basic Medical Sciences, Institute of Medical Virology, Wuhan University, Wuhan, ChinaState Key Laboratory of Virology, Hubei Province Key Laboratory of Allergy and Immunology, School of Basic Medical Sciences, Institute of Medical Virology, Wuhan University, Wuhan, ChinaState Key Laboratory of Virology, Hubei Province Key Laboratory of Allergy and Immunology, School of Basic Medical Sciences, Institute of Medical Virology, Wuhan University, Wuhan, ChinaSchool of Basic Medicine, Hubei University of Science and Technology, Xianning, ChinaState Key Laboratory of Virology, Hubei Province Key Laboratory of Allergy and Immunology, School of Basic Medical Sciences, Institute of Medical Virology, Wuhan University, Wuhan, ChinaDepartment of Microbiology and Immunology, Sealy Center for Vaccine Development and Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX, United StatesState Key Laboratory of Virology, Hubei Province Key Laboratory of Allergy and Immunology, School of Basic Medical Sciences, Institute of Medical Virology, Wuhan University, Wuhan, ChinaDepartment of Pathology and Laboratory Medicine, Temple University Lewis Katz School of Medicine, Philadelphia, PA, United StatesState Key Laboratory of Virology, Hubei Province Key Laboratory of Allergy and Immunology, School of Basic Medical Sciences, Institute of Medical Virology, Wuhan University, Wuhan, ChinaState Key Laboratory of Virology, Hubei Province Key Laboratory of Allergy and Immunology, School of Basic Medical Sciences, Institute of Medical Virology, Wuhan University, Wuhan, ChinaSchool of Basic Medicine, Hubei University of Science and Technology, Xianning, ChinaOpioid 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.https://www.frontiersin.org/article/10.3389/fimmu.2020.01253/fullopioidsHIVinnate immunityinterferonsmiRNAs |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
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 Wei Hou |
spellingShingle |
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 Wei Hou Methadone Inhibits Viral Restriction Factors and Facilitates HIV Infection in Macrophages Frontiers in Immunology opioids HIV innate immunity interferons miRNAs |
author_facet |
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 Wei Hou |
author_sort |
Mei-Rong Wang |
title |
Methadone Inhibits Viral Restriction Factors and Facilitates HIV Infection in Macrophages |
title_short |
Methadone Inhibits Viral Restriction Factors and Facilitates HIV Infection in Macrophages |
title_full |
Methadone Inhibits Viral Restriction Factors and Facilitates HIV Infection in Macrophages |
title_fullStr |
Methadone Inhibits Viral Restriction Factors and Facilitates HIV Infection in Macrophages |
title_full_unstemmed |
Methadone Inhibits Viral Restriction Factors and Facilitates HIV Infection in Macrophages |
title_sort |
methadone inhibits viral restriction factors and facilitates hiv infection in macrophages |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2020-07-01 |
description |
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. |
topic |
opioids HIV innate immunity interferons miRNAs |
url |
https://www.frontiersin.org/article/10.3389/fimmu.2020.01253/full |
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