title: Role of mu-opioids as cofactors in human immunodeficiency virus type 1 disease progression and neuropathogenesis.
abstract: About one third of acquired immunodeficiency syndrome cases in the USA have been attributed to the use of injected addictive drugs, frequently involving opioids like heroin and morphine, establishing them as significant predisposing risk factors for contracting human immunodeficiency virus type 1 (HIV-1). Accumulating evidence from in vitro and in vivo experimental systems indicates that opioids act in concert with HIV-1 proteins to exacerbate dysregulation of neural and immune cell function and survival through diverse molecular mechanisms. In contrast, the impact of opioid exposure and withdrawal on the viral life cycle and HIV-1 disease progression itself is unclear, with conflicting reports emerging from the simian immunodeficiency virus and simian-human immunodeficiency virus infection models. However, these studies suggest a potential role of opioids in elevated viral production. Because human microglia, astrocytes, CD4+ T lymphocytes, and monocyte-derived macrophages express opioid receptors, it is likely that intracellular signaling events triggered by morphine facilitate enhancement of HIV-1 infection in these target cell populations. This review highlights the biochemical changes that accompany prolonged exposure to and withdrawal from morphine that synergize with HIV-1 proteins to disrupt normal cellular physiological functions especially within the central nervous system. More importantly, it collates evidence from epidemiological studies, animal models, and heterologous cell systems to propose a mechanistic link between such physiological adaptations and direct modulation of HIV-1 production. Understanding the opioid-HIV-1 interface at the molecular level is vitally important in designing better treatment strategies for HIV-1-infected patients who abuse opioids.
authors: Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA 19102, USA.
authors: Anupam
authors: A
authors: Banerjee
authors: Marianne
authors: M
authors: Strazza
authors: Brian
authors: B
authors: Wigdahl
authors: Vanessa
authors: V
authors: Pirrone
authors: Olimpia
authors: O
authors: Meucci
authors: Michael R
authors: MR
authors: Nonnemacher
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000453:epidemiology / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000821:virology; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000009:adverse effects*; D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000821:virology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000821:virology; D015897:Comorbidity; D018450:Disease Progression; D016021:Epidemiologic Studies; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008251:Macaca; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000821:virology; D051379:Mice; D017628:Microglia / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000821:virology; D009020:Morphine / Q000008:administration & dosage / Q000009:adverse effects*; D009293:Opioid-Related Disorders / Q000453:epidemiology / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D011957:Receptors, Opioid / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D016097:Simian Acquired Immunodeficiency Syndrome / Q000453:epidemiology / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000187:drug effects* / Q000502:physiology; D013375:Substance Withdrawal Syndrome / Q000453:epidemiology / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D014481:United States; D014764:Viral Proteins / Q000276:immunology / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects* / Q000276:immunology
chemical_list: D000701:Analgesics, Opioid; D011957:Receptors, Opioid; D014764:Viral Proteins; D009020:Morphine