: In the United States, approximately 33% of individuals who are infected by the Human Immunodeficiency Virus (HIV) are intravenous drug abusers. Current evidence suggests that opioid abuse may promote the disease that occurs following this infection. We believe that the issue of the precise nature of the influence of opioid drugs of abuse in the development of HIV encephalitis is a critical question which remains largely unanswered. In this Program Project application, we propose four projects which will clarify the role of opioid abuse in the development of this disease process. Project 1 will address the combined influence of morphine and SIV infection on the expression of critical chemokines and chemokine receptors that play an important role in the development of SIV encephalitis. We will investigate the impact of both chronic morphine administration on expression of these crucial cytokines and their receptors at both the cellular and molecular level. Project 2 will investigate the effect of morphine on the pathogenesis of SIV infection in rhesus macaques. We will investigate the effect of viral load, immunophenotype of immune cells, and investigate the effect of drug treatment on the trafficking of infected cells into the CNS, lymph nodes, and other organs. Project 3 addresses the issue of the neuropathogenesis that is caused by a direct pathway that includes infection of macrophages, microglia, and astrocytes in the CNS, and an indirect pathway that involves dysregulation of immunomodulators and cytokines, and their downstream signaling pathways by viral proteins, such as gp120 and Tat, in both infected and uninfected bystander cells including neurons. In this research project we will focus our attention on a cytokine which has been implicated in direct and indirect pathways, and we will examine the effect of morphine on HIV-1 gene expression and replication, neuronal cell function, and apoptosis. Project 4 seeks to examine alterations in immune parameters following administration of morphine in both SIV-infected and non-infected macaques. An assessment of the immunological competence of animals in each treatment/infection group will be determined. Studies will include an analysis of the competence of both the acquired and innate immune systems. This application also includes administrative, animal, flow cytometry, and immunohistopathology cores to support the four research projects. PROGRAM PROJECT CHARACTERISTICS

National Institute of Health (NIH)
National Institute on Drug Abuse (NIDA)
Research Program Projects (P01)
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Study Section
Special Emphasis Panel (ZDA1-RXL-E (11))
Program Officer
Lawrence, Diane M
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Temple University
Schools of Medicine
United States
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Regan, Patrick M; Langford, Dianne; Khalili, Kamel (2016) Regulation and Functional Implications of Opioid Receptor Splicing in Opioid Pharmacology and HIV Pathogenesis. J Cell Physiol 231:976-85
Gabunia, Khatuna; Ellison, Stephen; Kelemen, Sheri et al. (2016) IL-19 Halts Progression of Atherosclerotic Plaque, Polarizes, and Increases Cholesterol Uptake and Efflux in Macrophages. Am J Pathol 186:1361-74
Cornwell, William D; Wagner, Wendeline; Lewis, Mark G et al. (2016) Effect of chronic morphine administration on circulating dendritic cells in SIV-infected rhesus macaques. J Neuroimmunol 295-296:30-40
Song, Changcheng; Wang, Qing; Song, Changzheng et al. (2015) Nucleocytoplasmic shuttling of valosin-containing protein (VCP/p97) regulated by its N domain and C-terminal region. Biochim Biophys Acta 1853:222-32
Cabral, Guy A; Rogers, Thomas J; Lichtman, Aron H (2015) Turning Over a New Leaf: Cannabinoid and Endocannabinoid Modulation of Immune Function. J Neuroimmune Pharmacol 10:193-203
Pitcher, Jonathan; Abt, Anna; Myers, Jaclyn et al. (2014) Neuronal ferritin heavy chain and drug abuse affect HIV-associated cognitive dysfunction. J Clin Invest 124:656-69
Bednar, Filip; Song, Changcheng; Bardi, Giuseppe et al. (2014) Cross-desensitization of CCR1, but not CCR2, following activation of the formyl peptide receptor FPR1. J Immunol 192:5305-13
Cornwell, William D; Lewis, Mark G; Fan, Xiaoxuan et al. (2013) Effect of chronic morphine administration on circulating T cell population dynamics in rhesus macaques. J Neuroimmunol 265:43-50
Dave, Rajnish S (2012) Morphine affects HIV-induced inflammatory response without influencing viral replication in human monocyte-derived macrophages. FEMS Immunol Med Microbiol 64:228-36
Rogers, Thomas J (2012) The molecular basis for neuroimmune receptor signaling. J Neuroimmune Pharmacol 7:722-4

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