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  1. Article ; Online: Effects of HIV-1 Tat on oligodendrocyte viability are mediated by CaMKIIβ-GSK3β interactions.

    Zou, Shiping / Balinang, Joyce M / Paris, Jason J / Hauser, Kurt F / Fuss, Babette / Knapp, Pamela E

    Journal of neurochemistry

    2019  Volume 149, Issue 1, Page(s) 98–110

    Abstract: Myelin disruptions are frequently reported in human immunodeficiency virus (HIV)-infected individuals and can occur in the CNS very early in the disease process. Immature oligodendrocytes (OLs) are quite sensitive to toxic increases in [ ... ...

    Abstract Myelin disruptions are frequently reported in human immunodeficiency virus (HIV)-infected individuals and can occur in the CNS very early in the disease process. Immature oligodendrocytes (OLs) are quite sensitive to toxic increases in [Ca
    MeSH term(s) Animals ; Calcium-Calmodulin-Dependent Protein Kinase Type 2/metabolism ; Cell Survival ; Glycogen Synthase Kinase 3 beta/metabolism ; HIV Infections/metabolism ; HIV Infections/pathology ; HIV-1 ; Mice ; Mice, Transgenic ; Oligodendroglia/metabolism ; Oligodendroglia/pathology ; tat Gene Products, Human Immunodeficiency Virus/metabolism
    Chemical Substances tat Gene Products, Human Immunodeficiency Virus ; Glycogen Synthase Kinase 3 beta (EC 2.7.11.1) ; Gsk3b protein, mouse (EC 2.7.11.1) ; Calcium-Calmodulin-Dependent Protein Kinase Type 2 (EC 2.7.11.17)
    Language English
    Publishing date 2019-03-15
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 80158-6
    ISSN 1471-4159 ; 0022-3042 ; 1474-1644
    ISSN (online) 1471-4159
    ISSN 0022-3042 ; 1474-1644
    DOI 10.1111/jnc.14668
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Productive infection of human neural progenitor cells by R5 tropic HIV-1: opiate co-exposure heightens infectivity and functional vulnerability.

    Balinang, Joyce M / Masvekar, Ruturaj R / Hauser, Kurt F / Knapp, Pamela E

    AIDS (London, England)

    2017  Volume 31, Issue 6, Page(s) 753–764

    Abstract: Objective: HIV type-1 (HIV-1) causes a spectrum of central nervous system (CNS) complications; many are worsened by opiate co-exposure. Human neural progenitor cells (hNPCs) give rise to all CNS neurons and macroglia. We tested the hypothesis that hNPC ... ...

    Abstract Objective: HIV type-1 (HIV-1) causes a spectrum of central nervous system (CNS) complications; many are worsened by opiate co-exposure. Human neural progenitor cells (hNPCs) give rise to all CNS neurons and macroglia. We tested the hypothesis that hNPC maturation and fate are altered by HIV and opiates, contributing to HIV-1-related neuropathology. Reports of hNPC infection remain controversial. We rigorously examined this question, testing whether hNPCs propogated infection, and whether HIV affected hNPCs absent their infection.
    Design and methods: Primary hNPCs were characterized over multiple passages. Following R5 HIV-1BaL exposure, p24, Nef, and tat assays monitored infection; a serial dilution approach tested infection transfer to naive hNPCs. Bromodeoxyuridine uptake, population doubling time, and immunostaining assessed proliferation and differentiation. Morphine co-exposure assessed opiate interactions. Supernatant from HIV-1BaL-infected PBMCs (HIVsup), HIV-1BaL, and ultraviolet light-inactivated HIVsup were compared to test effects of inflammatory milieu versus virus or infection per se.
    Results: The hNPCs (CD4/CD8/Iba/CXC3CL1/CD11b) were infectable and could transfer infection to naive hNPCs. Infection was partly blocked by maraviroc, implicating CCR5. HIVsup reduced hNPC proliferation and caused premature differentiation into neurons/astroglia. Effects on proliferation were due to soluble factors/viral proteins, not infection per se. Morphine co-exposure exacerbated certain functional consequences of HIVsup, and sustained the infection of hNPCs.
    Conclusion: hNPCs can be infected and propagate virus in vitro. hNPCs or their progeny may represent an underappreciated viral reservoir. Factors from infected cells alter hNPC proliferation and neural cell maturation, which likely compromises CNS structure and function. Morphine-HIV interactions may worsen dysfunction and sustain infection.
    Language English
    Publishing date 2017-03-27
    Publishing country England
    Document type Journal Article
    ZDB-ID 639076-6
    ISSN 1473-5571 ; 0269-9370 ; 1350-2840
    ISSN (online) 1473-5571
    ISSN 0269-9370 ; 1350-2840
    DOI 10.1097/QAD.0000000000001398
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Differential expression of the alternatively spliced OPRM1 isoform μ-opioid receptor-1K in HIV-infected individuals.

    Dever, Seth M / Costin, Blair N / Xu, Ruqiang / El-Hage, Nazira / Balinang, Joyce / Samoshkin, Alexander / O'Brien, Megan A / McRae, Marypeace / Diatchenko, Luda / Knapp, Pamela E / Hauser, Kurt F

    AIDS (London, England)

    2014  Volume 28, Issue 1, Page(s) 19–30

    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 ( ... ...

    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.
    Methods and 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.
    Conclusion: 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.
    MeSH term(s) AIDS Dementia Complex/pathology ; HIV Infections/complications ; HIV Infections/pathology ; Humans ; Protein Isoforms/biosynthesis ; Protein Isoforms/genetics ; RNA Splicing ; Real-Time Polymerase Chain Reaction ; Receptors, Opioid, mu/biosynthesis ; Receptors, Opioid, mu/genetics
    Chemical Substances OPRM1 protein, human ; Protein Isoforms ; Receptors, Opioid, mu
    Language English
    Publishing date 2014-01-10
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 639076-6
    ISSN 1473-5571 ; 0269-9370 ; 1350-2840
    ISSN (online) 1473-5571
    ISSN 0269-9370 ; 1350-2840
    DOI 10.1097/QAD.0000000000000113
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Deep Sequencing Reveals Central Nervous System Compartmentalization in Multiple Transmitted/Founder Virus Acute HIV-1 Infection.

    Tovanabutra, Sodsai / Sirijatuphat, Rujipas / Pham, Phuc T / Bonar, Lydia / Harbolick, Elizabeth A / Bose, Meera / Song, Hongshuo / Chang, David / Oropeza, Celina / O'Sullivan, Anne Marie / Balinang, Joyce / Kroon, Eugene / Colby, Donn J / Sacdalan, Carlo / Hellmuth, Joanna / Chan, Phillip / Prueksakaew, Peeriya / Pinyakorn, Suteeraporn / Jagodzinski, Linda L /
    Sutthichom, Duanghathai / Pattamaswin, Suwanna / de Souza, Mark / Gramzinski, Robert A / Kim, Jerome H / Michael, Nelson L / Robb, Merlin L / Phanuphak, Nittaya / Ananworanich, Jintanat / Valcour, Victor / Kijak, Gustavo H / Sanders-Buell, Eric / Spudich, Serena

    Cells

    2019  Volume 8, Issue 8

    Abstract: HIV-1 disseminates to a broad range of tissue compartments during acute HIV-1 infection (AHI). The central nervous system (CNS) can serve as an early and persistent site of viral replication, which poses a potential challenge for HIV-1 remission ... ...

    Abstract HIV-1 disseminates to a broad range of tissue compartments during acute HIV-1 infection (AHI). The central nervous system (CNS) can serve as an early and persistent site of viral replication, which poses a potential challenge for HIV-1 remission strategies that target the HIV reservoir. CNS compartmentalization is a key feature of HIV-1 neuropathogenesis. Thus far, the timing of how early CNS compartmentalization develops after infection is unknown. We examined whether HIV-1 transmitted/founder (T/F) viruses differ between CNS and blood during AHI using single-genome sequencing of envelope gene and further examined subregions in
    MeSH term(s) Adult ; Female ; Genes, env/genetics ; Genes, pol/genetics ; HIV Infections/blood ; HIV Infections/cerebrospinal fluid ; HIV-1/genetics ; HIV-1/physiology ; High-Throughput Nucleotide Sequencing ; Humans ; Male ; RNA, Viral/blood ; Sequence Analysis, RNA ; Virus Replication ; Young Adult
    Chemical Substances RNA, Viral
    Language English
    Publishing date 2019-08-15
    Publishing country Switzerland
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2661518-6
    ISSN 2073-4409 ; 2073-4409
    ISSN (online) 2073-4409
    ISSN 2073-4409
    DOI 10.3390/cells8080902
    Database MEDical Literature Analysis and Retrieval System OnLINE

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