Effect of μ-opioid agonist DAMGO on surface CXCR4 and HIV-1 replication in TF-1 human bone marrow progenitor cells

被引：7

作者：

Strazza M. ^{[1
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,3
]}

Banerjee A. ^{[1
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,3
]}

Alexaki A. ^{[1
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,3
]}

Passic S.R. ^{[1
,2
,3
]}

Meucci O. ^{[1
,2
,3
,4
]}

Pirrone V. ^{[1
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,3
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Wigdahl B. ^{[1
,2
,3
]}

Nonnemacher M.R. ^{[1
,2
,3
]}

机构：

[1] Department of Microbiology and Immunology, Drexel University College of Medicine, 245 N. 15th Street, MS# 1013A, Philadelphia, 19102, PA

[2] Center for Molecular Virology and Translational Neuroscience, Drexel University College of Medicine, Philadelphia, 19102, PA

[3] Center for Neuroimmunology and CNS Therapeutics, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, 19102, PA

[4] Department of Pharmacology and Physiology, Drexel University College of Medicine, Philadelphia, 19102, PA

来源：

BMC Research Notes | / 7卷 / 1期

基金：

美国国家卫生研究院;

关键词：

Bone marrow; CXCR4; DAMGO; Human immunodeficiency virus type 1 (HIV-1); μ-opioid receptor (MOR-1);

D O I：

10.1186/1756-0500-7-752

中图分类号：

学科分类号：

摘要：

Background: Approximately one-third of the AIDS cases in the United States have been attributed to the use of injected drugs, frequently involving the abuse of opioids. Consequently, it is critical to address whether opioid use directly contributes to altered susceptibility to HIV-1 beyond the increased risk of exposure. Previous in vitro and in vivo studies addressing the role of μ-opioid agonists in altering levels of the co-receptor CXCR4 and subsequent HIV-1 replication have yielded contrasting results. The bone marrow is believed to be a potential anatomical sanctuary for HIV-1. Methods: The well-characterized CD34+CD38+ human bone marrow-derived hematopoietic progenitor cell line TF-1 was used as a model to investigate the effects of the μ-opioid receptor-specific peptide DAMGO (D-Ala2, N-Me-Phe4, Gly5-ol-enkephalin) on CXCR4 expression as well as infection of undifferentiated human hematopoietic progenitor cells. Results: The results revealed the presence of the μ-opioid receptor-1 isoform (MOR-1) on the surface of TF-1 cells. Furthermore, immunostaining revealed that the majority of TF-1 cells co-express MOR-1 and CXCR4, and a subpopulation of these double-positive cells express the two receptors in overlapping membrane domains. Three subpopulations of TF-1 cells were categorized based on their levels of surface CXCR4 expression, defined as non-, low-, and high-expressing. Flow cytometry indicated that treatment with DAMGO resulted in a shift in the relative proportion of CXCR4+ cells to the low-expressing phenotype. This result correlated with a >3-fold reduction in replication of the X4 HIV-1 strain IIIB, indicating a role for the CXCR4 high-expression subpopulation in sustaining infection within this progenitor cell line. Conclusions: These experiments provide insight into the impact of μ-opioid exposure with respect to inhibition of viral replication in this human TF-1 bone marrow progenitor cell line model. © 2014 Strazza et al.

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