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  1. Article ; Online: HIV infection of non-classical cells in the brain.

    Wahl, Angela / Al-Harthi, Lena

    Retrovirology

    2023  Volume 20, Issue 1, Page(s) 1

    Abstract: HIV-associated neurological disorders (HAND) affect up to 50% of people living with HIV (PLWH), even in the era of combination antiretroviral therapy (cART). HIV-DNA can be detected in the cerebral spinal fluid (CSF) of approximately half of aviremic ART- ...

    Abstract HIV-associated neurological disorders (HAND) affect up to 50% of people living with HIV (PLWH), even in the era of combination antiretroviral therapy (cART). HIV-DNA can be detected in the cerebral spinal fluid (CSF) of approximately half of aviremic ART-suppressed PLWH and its presence is associated with poorer neurocognitive performance. HIV DNA + and HIV RNA + cells have also been observed in postmortem brain tissue of individuals with sustained cART suppression. In this review, we provide an overview of how HIV invades the brain and HIV infection of resident brain glial cells (astrocytes and microglia). We also discuss the role of resident glial cells in persistent neuroinflammation and HAND in PLWH and their potential contribution to the HIV reservoir. HIV eradication strategies that target persistently infected glia cells will likely be needed to achieve HIV cure.
    MeSH term(s) Humans ; HIV Infections/complications ; Brain ; Macrophages ; HIV ; Monocytes ; Nervous System Diseases
    Language English
    Publishing date 2023-01-13
    Publishing country England
    Document type Journal Article ; Review ; Research Support, N.I.H., Extramural
    ZDB-ID 2142602-8
    ISSN 1742-4690 ; 1742-4690
    ISSN (online) 1742-4690
    ISSN 1742-4690
    DOI 10.1186/s12977-023-00616-9
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Hyperactivity of medial prefrontal cortex pyramidal neurons occurs in a mouse model of early-stage Alzheimer's disease without

    Choudhury, Nasreen / Chen, Lihua / Al-Harthi, Lena / Hu, Xiu-Ti

    Frontiers in pharmacology

    2023  Volume 14, Page(s) 1194869

    Abstract: The normal function of the medial prefrontal cortex (mPFC) is essential for regulating neurocognition, but it is disrupted in the early stages of Alzheimer's disease (AD) before the accumulation of Aβ and the appearance of symptoms. Despite this, little ... ...

    Abstract The normal function of the medial prefrontal cortex (mPFC) is essential for regulating neurocognition, but it is disrupted in the early stages of Alzheimer's disease (AD) before the accumulation of Aβ and the appearance of symptoms. Despite this, little is known about how the functional activity of medial prefrontal cortex pyramidal neurons changes as Alzheimer's disease progresses during aging. We used electrophysiological techniques (patch-clamping) to assess the functional activity of medial prefrontal cortex pyramidal neurons in the brain of 3xTg-Alzheimer's disease mice modeling early-stage Alzheimer's disease without Aβ accumulation. Our results indicate that firing rate and the frequency of spontaneous excitatory postsynaptic currents (sEPSCs) were significantly increased in medial prefrontal cortex neurons from young Alzheimer's disease mice (4-5-month, equivalent of <30-year-old humans) compared to age-matched control mice. Blocking ionotropic glutamatergic NMDA receptors, which regulate neuronal excitability and Ca
    Language English
    Publishing date 2023-07-03
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2587355-6
    ISSN 1663-9812
    ISSN 1663-9812
    DOI 10.3389/fphar.2023.1194869
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Wnt/β-Catenin Protects Lymphocytes from HIV-Mediated Apoptosis via Induction of Bcl-xL.

    Albalawi, Yasmeen A / Narasipura, Srinivas D / Al-Harthi, Lena

    Viruses

    2022  Volume 14, Issue 7

    Abstract: HIV infection mediates the apoptosis of lymphocytes, the mechanism of which is multifaceted. Here, we evaluated the role of Wnt/β-catenin signaling in HIV-associated T cell apoptosis, as Wnt/β-catenin regulates the transcriptional activity of genes ... ...

    Abstract HIV infection mediates the apoptosis of lymphocytes, the mechanism of which is multifaceted. Here, we evaluated the role of Wnt/β-catenin signaling in HIV-associated T cell apoptosis, as Wnt/β-catenin regulates the transcriptional activity of genes impacting apoptosis. We specifically investigated the role of the Wnt/β-catenin pathway in the HIV-associated apoptosis of CD4+ T cells and CD4dimCD8bright T cells, a population that is infected by HIV. We found that the induction of β-catenin, via a 6-bromoindirubin-3-oxime (BIO), significantly rescued HIV-infected CD4+ and CD4dimCD8bright T cells from apoptosis by >40−50%. Further, a small-molecule inhibitor of the Wnt/β-catenin pathway (PNU-74654) reversed BIO-mediated protection from HIV-associated apoptosis. BIO also induced Bcl-xL, an anti-apoptotic protein, and a target gene of Wnt/β-catenin, in CD4+ and CD4dimCD8bright T cells by approximately 3-fold. Inhibiting Bcl-xL by WEHI-539 abrogated β-catenin-mediated apoptotic protection in infected CD4+ and CD4dimCD8bright T cells. Collectively, these findings demonstrate that engaging Wnt/β-catenin signaling in HIV-infected T cells protects them from HIV-associated apoptosis by inducing Bcl-xL.
    MeSH term(s) Apoptosis ; CD4-Positive T-Lymphocytes/metabolism ; HIV Infections ; Humans ; Wnt Signaling Pathway ; beta Catenin/genetics ; beta Catenin/metabolism
    Chemical Substances beta Catenin
    Language English
    Publishing date 2022-07-02
    Publishing country Switzerland
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2516098-9
    ISSN 1999-4915 ; 1999-4915
    ISSN (online) 1999-4915
    ISSN 1999-4915
    DOI 10.3390/v14071469
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: HIV-Induced Hyperactivity of Striatal Neurons Is Associated with Dysfunction of Voltage-Gated Calcium and Potassium Channels at Middle Age.

    Khodr, Christina E / Chen, Lihua / Al-Harthi, Lena / Hu, Xiu-Ti

    Membranes

    2022  Volume 12, Issue 8

    Abstract: Despite combination antiretroviral therapy, HIV-associated neurocognitive disorders (HAND) occur in ~50% of people living with HIV (PLWH), which are associated with dysfunction of the corticostriatal pathway. The mechanism by which HIV alters the ... ...

    Abstract Despite combination antiretroviral therapy, HIV-associated neurocognitive disorders (HAND) occur in ~50% of people living with HIV (PLWH), which are associated with dysfunction of the corticostriatal pathway. The mechanism by which HIV alters the neuronal activity in the striatum is unknown. The goal of this study is to reveal the dysfunction of striatal neurons in the context of neuroHIV during aging. Using patch-clamping electrophysiology, we evaluated the functional activity of medium spiny neurons (MSNs), including firing, Ca
    Language English
    Publishing date 2022-07-28
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2614641-1
    ISSN 2077-0375
    ISSN 2077-0375
    DOI 10.3390/membranes12080737
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  5. Article: Triumeq Increases Excitability of Pyramidal Neurons in the Medial Prefrontal Cortex by Facilitating Voltage-Gated Ca

    Chen, Lihua / Al-Harthi, Lena / Hu, Xiu-Ti

    Frontiers in pharmacology

    2021  Volume 11, Page(s) 617149

    Abstract: Combination antiretroviral therapy (cART) suppresses HIV-1 replication, improves immune function, and prolongs the life of people living with HIV (PLWH). However, cART also induces neurotoxicity that could complicate HIV-induced neurodegeneration while ... ...

    Abstract Combination antiretroviral therapy (cART) suppresses HIV-1 replication, improves immune function, and prolongs the life of people living with HIV (PLWH). However, cART also induces neurotoxicity that could complicate HIV-induced neurodegeneration while reduce its therapeutic efficacy in treating HIV/AIDS. Triumeq is a first-line cART regimen, which is co-formulated by three antiretroviral drugs (ARVs), lamivudine (3TC), abcavir (ABC), and dolutegravir (DTG). Little is known about potential side effects of ARVs on the brain (including those co-formulating Triumeq), and their mechanisms impacting neuronal activity. We assessed acute (
    Language English
    Publishing date 2021-01-28
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2587355-6
    ISSN 1663-9812
    ISSN 1663-9812
    DOI 10.3389/fphar.2020.617149
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  6. Article: HIV in the Brain: Identifying Viral Reservoirs and Addressing the Challenges of an HIV Cure.

    Ash, Michelle K / Al-Harthi, Lena / Schneider, Jeffrey R

    Vaccines

    2021  Volume 9, Issue 8

    Abstract: Advances in antiretroviral therapy have prolonged the life of people living with HIV and diminished the level of virus in these individuals. Yet, HIV quickly rebounds after disruption and/or cessation of treatment due to significant cellular and ... ...

    Abstract Advances in antiretroviral therapy have prolonged the life of people living with HIV and diminished the level of virus in these individuals. Yet, HIV quickly rebounds after disruption and/or cessation of treatment due to significant cellular and anatomical reservoirs for HIV, which underscores the challenge for HIV cure strategies. The central nervous system (CNS), in particular, is seeded with HIV within 1-2 weeks of infection and is a reservoir for HIV. In this review, we address the paradigm of HIV reservoirs in the CNS and the relevant cell types, including astrocytes and microglia, that have been shown to harbor viral infection even with antiretroviral treatment. In particular, we focus on developmental aspects of astrocytes and microglia that lead to their susceptibility to infection, and how HIV infection propagates among these cells. We also address challenges of measuring the HIV latent reservoir, advances in viral detection assays, and how curative strategies have evolved in regard to the CNS reservoir. Current curative strategies still require optimization to reduce or eliminate the HIV CNS reservoir, and may also contribute to levels of neuroinflammation that lead to cognitive decline. With this in mind, the latent HIV reservoir in the brain should remain a prominent focus when assessing treatment options and overall viral burden in the clinic, especially in the context of HIV-associated neurocognitive disorders (HAND).
    Language English
    Publishing date 2021-08-05
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2703319-3
    ISSN 2076-393X
    ISSN 2076-393X
    DOI 10.3390/vaccines9080867
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Letter to Editor.

    Al-Harthi, Lena / Nath, Avindra

    Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology

    2018  Volume 14, Issue 1, Page(s) 6

    MeSH term(s) Astrocytes ; DNA ; HIV Infections ; HIV-1 ; Humans ; Macrophages
    Chemical Substances DNA (9007-49-2)
    Language English
    Publishing date 2018-12-12
    Publishing country United States
    Document type Letter ; Comment
    ZDB-ID 2227405-4
    ISSN 1557-1904 ; 1557-1890
    ISSN (online) 1557-1904
    ISSN 1557-1890
    DOI 10.1007/s11481-018-09827-w
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  8. Article ; Online: CD4

    Albalawi, Yasmeen A / Narasipura, Srinivas D / Olivares, Leannie J / Al-Harthi, Lena

    Journal of virology

    2022  Volume 96, Issue 15, Page(s) e0080422

    Abstract: ... ...

    Abstract CD4
    MeSH term(s) Animals ; Brain/immunology ; Brain/metabolism ; Brain/virology ; CD4 Antigens ; CD8 Antigens ; CD8-Positive T-Lymphocytes/cytology ; CD8-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/metabolism ; CX3C Chemokine Receptor 1/metabolism ; Cell Movement ; HIV Infections/immunology ; HIV Infections/virology ; HIV-1/pathogenicity ; Humans ; Interleukin Receptor Common gamma Subunit/deficiency ; Mice ; Mice, Inbred NOD ; Mice, SCID ; Proviruses/genetics ; Proviruses/isolation & purification ; Receptors, CXCR3/metabolism ; Receptors, Lymphocyte Homing/metabolism ; Viral Tropism
    Chemical Substances CD4 Antigens ; CD8 Antigens ; CX3C Chemokine Receptor 1 ; Cx3cr1 protein, mouse ; Cxcr3 protein, mouse ; Il2rg protein, mouse ; Interleukin Receptor Common gamma Subunit ; Receptors, CXCR3 ; Receptors, Lymphocyte Homing
    Language English
    Publishing date 2022-07-19
    Publishing country United States
    Document type Journal Article
    ZDB-ID 80174-4
    ISSN 1098-5514 ; 0022-538X
    ISSN (online) 1098-5514
    ISSN 0022-538X
    DOI 10.1128/jvi.00804-22
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 609: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
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  9. Article ; Online: Correction to: Astrocytes as an HIV CNS reservoir: highlights and reflections of an NIMH-sponsored symposium.

    Al-Harthi, Lena / Joseph, Jeymohan / Nath, Avindra

    Journal of neurovirology

    2019  Volume 25, Issue 4, Page(s) 616

    Abstract: In the original article the name of author Lena Al-Harthi was misspelled. It is correct here. ...

    Abstract In the original article the name of author Lena Al-Harthi was misspelled. It is correct here.
    Language English
    Publishing date 2019-03-14
    Publishing country United States
    Document type Published Erratum
    ZDB-ID 1283265-0
    ISSN 1538-2443 ; 1355-0284
    ISSN (online) 1538-2443
    ISSN 1355-0284
    DOI 10.1007/s13365-019-00726-1
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 4426: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

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  10. Article ; Online: The anti-HIV drug abacavir stimulates β-catenin activity in osteoblast lineage cells.

    Olali, Arnold Z / Wallace, Jennillee / Gonzalez, Hemil / Carpenter, Kelsey A / Patel, Niyati / Winchester, Lee C / Podany, Anthony T / Venkatesh, Ishwarya / Narasipura, Srinivas D / Al-Harthi, Lena / Ross, Ryan D

    JBMR plus

    2024  Volume 8, Issue 5, Page(s) ziae037

    Abstract: Bone mineral density (BMD) loss in people living with HIV occurs with the initiation of combined antiretroviral therapy (cART), particularly with tenofovir disoproxil fumarate (TDF) containing cART. Switching from TDF to abacavir (ABC) or dolutegravir ( ... ...

    Abstract Bone mineral density (BMD) loss in people living with HIV occurs with the initiation of combined antiretroviral therapy (cART), particularly with tenofovir disoproxil fumarate (TDF) containing cART. Switching from TDF to abacavir (ABC) or dolutegravir (DTG) leads to increased BMD. Whether BMD gains are due to cessation of TDF or anabolic effects of ABC or DTG is unclear. We investigated the effects of ABC and DTG on osteoblast lineage cells
    Language English
    Publishing date 2024-03-19
    Publishing country England
    Document type Journal Article
    ISSN 2473-4039
    ISSN (online) 2473-4039
    DOI 10.1093/jbmrpl/ziae037
    Database MEDical Literature Analysis and Retrieval System OnLINE

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