title: Differential expression of the alternatively spliced OPRM1 isoform μ-opioid receptor-1K in HIV-infected individuals.
abstract: OBJECTIVE
  We previously examined the expression of specific C-terminal μ-opioid receptor (MOR) splice variants in human central nervous system cell types and HIV-infected brain tissue from individuals with neurocognitive impairment ± HIV encephalitis (HIVE). In the present study, we examined the N-terminal splice variant MOR-1K, which mediates excitatory cellular signaling.
  
  
  RESULTS
  We found segregation of expression ranging from undetectable to seemingly exclusive across nervous system cell types compared to the pool of C-terminal MOR splice variants using the real-time polymerase chain reaction (RT-PCR). Expression of MOR-1K mRNA was also increased in HIV-infected individuals with combined neurocognitive impairment and HIVE compared with the other groups. MOR-1K expression correlated with the level of patient neurocognitive impairment, whereas the pool of C-terminal MOR splice variants did not. HIVE was also associated with increased expression of the inflammatory mediators MCP-1, MCP-2, and RANTES, but not the host HIV coreceptors CXCR4 and CCR5 or the CD4 receptor using qRT-PCR. Network analysis of microarray data from these same patients revealed filamin A (FLNA) as a possible interaction partner with MOR-1K, and FLNA gene expression was also found to be upregulated in HIVE using qRT-PCR. Overexpression of FLNA in HEK293 cells redistributed MOR-1K from intracellular compartments to the cell surface.
  
  
  CONCLUSIONS
  These results suggest that HIVE, and neurocognitive impairment depending on its severity, are associated with enhanced MOR-1K signaling through both increased expression and trafficking to the cell surface, which may alter the contribution of MOR receptor isoforms and exacerbate the effects of MOR activation in neuroAIDS.
authors.affiliation: aDepartment of Pharmacology & Toxicology bDepartment of Anatomy & Neurobiology, Virginia Commonwealth University School of Medicine, Richmond, Virginia cCenter for Neurosensory Disorders, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina dDepartment of Pharmacotherapy & Outcomes Science, Virginia Commonwealth University School of Pharmacy eInstitute for Drug & Alcohol Studies, Virginia Commonwealth University, Richmond, Virginia, USA.
authors.forename: Seth M
authors.initials: SM
authors.lastname: Dever
authors.forename: Blair N
authors.initials: BN
authors.lastname: Costin
authors.forename: Ruqiang
authors.initials: R
authors.lastname: Xu
authors.forename: Nazira
authors.initials: N
authors.lastname: El-Hage
authors.forename: Joyce
authors.initials: J
authors.lastname: Balinang
authors.forename: Alexander
authors.initials: A
authors.lastname: Samoshkin
authors.forename: Megan A
authors.initials: MA
authors.lastname: O'Brien
authors.forename: Marypeace
authors.initials: M
authors.lastname: McRae
authors.forename: Luda
authors.initials: L
authors.lastname: Diatchenko
authors.forename: Pamela E
authors.initials: PE
authors.lastname: Knapp
authors.forename: Kurt F
authors.initials: KF
authors.lastname: Hauser
mesh_terms: D015526:AIDS Dementia Complex / Q000473:pathology*; D015658:HIV Infections / Q000150:complications* / Q000473:pathology*; D006801:Humans; D020033:Protein Isoforms / Q000096:biosynthesis / Q000235:genetics; D012326:RNA Splicing; D060888:Real-Time Polymerase Chain Reaction; D017450:Receptors, Opioid, mu / Q000096:biosynthesis* / Q000235:genetics
chemical_list: C485764:OPRM1 protein, human; D020033:Protein Isoforms; D017450:Receptors, Opioid, mu