Differential expression and HIV-1 regulation of μ-opioid receptor splice variants across human central nervous system cell types

• Published in: Journal of neurovirology 2012-06, Vol.18 (3), p.181-190
• Main Authors: Dever, Seth M., Xu, Ruqiang, Fitting, Sylvia, Knapp, Pamela E., Hauser, Kurt F.
• Format: Article
• Language: English
• Subjects: Alternative Splicing; Astrocytes - metabolism; Astrocytes - virology; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Cognition; Gene Expression Regulation; HEK293 Cells; HIV Infections - genetics; HIV Infections - metabolism; HIV Infections - virology; HIV-1 - physiology; Human viral diseases; Humans; Immunology; Infectious Diseases; Medical sciences; Microglia - metabolism; Microglia - virology; Morphine - pharmacology; Neurology; Neurons - metabolism; Neurons - virology; Neurosciences; Organ Specificity; Protein Isoforms - genetics; Protein Isoforms - metabolism; Receptors, Opioid, mu - genetics; Receptors, Opioid, mu - metabolism; Recombinant Fusion Proteins - genetics; Recombinant Fusion Proteins - metabolism; RNA, Messenger - biosynthesis; Signal Transduction; Transfection; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Viral diseases of the nervous system; Virology
• ISSN: 1355-0284; 1538-2443
• DOI: 10.1007/s13365-012-0096-z

The μ-opioid receptor (MOR) is known to undergo extensive alternative splicing as numerous splice variants of MOR have been identified. However, the functional significance of MOR variants, as well as how splice variants other than MOR-1 might differentially regulate human immunodeficiency virus type-1 (HIV-1) pathogenesis in the central nervous system (CNS), or elsewhere, has largely been ignored. Our findings suggest that there are specific differences in the MOR variant expression profile among CNS cell types, and that the expression levels of these variants are differentially regulated by HIV-1. While MOR-1A mRNA was detected in astroglia, microglia, and neurons, MOR-1 and MOR-1X were only found in astroglia. Expression of the various forms of MOR along with the chimeric G protein qi5 in HEK-293T cells resulted in differences in calcium/NFAT signaling with morphine treatment, suggesting that MOR variant expression might underlie functional differences in MOR-effector coupling and intracellular signaling across different cell types. Furthermore, the data suggest that the expression of MOR-1 and other MOR variants may also be differentially regulated in the brains of HIV-infected subjects with varying levels of neurocognitive impairment. Overall, the results reveal an unexpected finding that MOR-1 may not be the predominant form of MOR expressed by some CNS cell types and that other splice variants of MOR-1, with possible differing functions, may contribute to the diversity of MOR-related processes in the CNS.