Heroin inhibits HIV-restriction miRNAs and enhances HIV infection of macrophages

Wang, Xu; Ma, Tongcui; Li, Jieliang; Zhou, Yu; Geller, Ellen B.; Adler, Martin W.; Peng, Jinsong; Wang, Zhou; Zhou, Dun-Jin; Ho, Wen‐Zhe

doi:10.3389/fmicb.2015.01230

Cited by 26 publications

(23 citation statements)

References 70 publications

(96 reference statements)

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“…In our study, we found that methadone treatment of macrophages suppressed the expression of IFN-β and IFN-λ2 ( Figure 3 ). This finding supports the earlier observation that morphine or heroin could significantly inhibit the expression of endogenous IFNs in macrophages ( 49 , 55 ). APOBEC (apolipoprotein B mRNA-editing enzymecatalytic polypeptide-like protein) family members inhibit retroviruses replication by deamination to convert cytidine(C) to uridine (U) of viral DNA ( 56 ), among which APOBEC3F and APOBEC3G can restrict HIV replication in both CD4+ T cells and macrophages ( 57 , 58 ).…”

Section: Discussionsupporting

confidence: 93%

Methadone Inhibits Viral Restriction Factors and Facilitates HIV Infection in Macrophages

Wang

Luo

et al. 2020

Front. Immunol.

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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.

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Section: Discussionsupporting

confidence: 93%

Methadone Inhibits Viral Restriction Factors and Facilitates HIV Infection in Macrophages

Wang

Luo

et al. 2020

Front. Immunol.

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“…Studies at the molecular level prove that morphine inhibits the production of several transcription factors and induces miRNAs that inhibit inflammatory reactions. The enhancing effects of heroin on HIV replication processes are based on the heroin inhibition processes of certain miRNAs (specifically, miRNA-28, miRNA-125b, miRNA-150 and miRNA-382) that normally limit the replication of viral particles [ 25 ]. Clinical studies confirm lower levels of several biologically significant miRNAs (in particular, miRNA-582-5p and miRNA-590-5p) in the blood of long-term heroin users [ 26 ].…”

Section: Immunomodulatory Effects Of Opioid Agentsmentioning

confidence: 99%

Impact of Opioid Use in Hematological Malignancies: Clinical, Immunological and Concomitant Aspects

Tregubenko

Zvonarev

2020

J Hematol

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Opioid agents play a unique role in pain and symptom management for cancer patients. Research shows that opiate use, especially when associated with underlying cancer, has significant effects on hematological parameters. These changes may lead to greater risk for immunosuppression, tumor growth and progression of metastatic processes. The aim of this review is to explore the effects of opiates on various metabolic and biological processes, as well as the hematopoietic system, especially in cancer patients. Our findings demonstrate that the tumor-promoting effects of opiates remain contradictory, as both growth-promoting and anti-tumor effects have been observed. However, available data suggest that opiates can facilitate the proliferation and migration of tumor cells, and understanding of this process on cancer treatment is tremendously important.

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“…Similarly, endogenous opioid peptides such as β endorphin, endomorphin-1, and dynorphin enhance HIV expression [64–67]. Multiple studies have shown that opioid receptor antagonists can reverse the proviral effects of morphine, methadone, heroin, or opioid peptides [44, 59, 61, 62, 64, 65, 68–70]. Unfortunately, many drugs of abuse – including synthetic opioids – have not been evaluated thoroughly.…”

Section: Hiv and Substance Abusementioning

confidence: 99%

“…The ability of opioids to modulate epigenetic changes – particularly microRNA expression – highlights another mechanism by which opioids impact viral infection. For example, morphine and heroin inhibit the expression of anti-HIV microRNAs that target the 3’UTR of viral transcripts [59, 61, 70]. Similarly, opioids inhibit anti-HIV microRNAs that stimulate replication of latent HIV in resting CD4 + T cells and monocytes [61, 83].…”

Section: Hiv and Substance Abusementioning

confidence: 99%

“…Additionally, synthetic opioids may impact viral disease progression indirectly through drug-drug interactions and/or by reduced antiviral activity, although this remains to be explored in detail. Importantly, opioids can modulate epigenetic changes such as microRNA expression that impact viral infection [59, 61, 70, 83, 97]. However, the cellular pathways altered by synthetic opioid use have not been explored in vivo , thereby hindering the development of novel therapeutic strategies to treat complex virus-opioid interactions and the life-threatening comorbidities associated with recreational opioid use.…”

Section: Research Prioritiesmentioning

confidence: 99%

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Synthetic Opioid Use and Common Injection-associated Viruses: Expanding the Translational Research Agenda

Blackard

Brown

Lyons

2019

CHR

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The US is in the midst of a major epidemic of opioid addiction and related comorbidities. People with opioid use disorder (OUD) are at significant risk for transmission of several blood-borne pathogens including the human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV). Commonly abused opioids and their receptors promote viral replication and virus-mediated pathology. However, most studies demonstrating an adverse effect of drugs of abuse have been conducted in vitro, the specific effects of synthetic opioids on viral replication have been poorly characterized, and the evaluation of opioid-virus interactions in clinically relevant populations is rare. Rigorous characterization of the interactions among synthetic opioids, host cells, and common injection-associated viral infections will require an interdisciplinary research approach and translational studies conducted on humans. Such research promises to improve clinical management paradigms for difficult-to-treat populations, facilitate rational public health policies given severely strained resources, and reveal additional pathways for novel target-specific therapeutic interventions. This mini-review examines the published literature on the effects of opioids on HIV, HBV, and HCV pathogenesis and proposes a series of scientific questions and considerations to establish a translational research agenda focused on opioid-virus interactions.

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Heroin inhibits HIV-restriction miRNAs and enhances HIV infection of macrophages

Cited by 26 publications

References 70 publications

Methadone Inhibits Viral Restriction Factors and Facilitates HIV Infection in Macrophages

Methadone Inhibits Viral Restriction Factors and Facilitates HIV Infection in Macrophages

Impact of Opioid Use in Hematological Malignancies: Clinical, Immunological and Concomitant Aspects

Synthetic Opioid Use and Common Injection-associated Viruses: Expanding the Translational Research Agenda

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