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HIV Neuropathogenesis

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https://www.readbyqxmd.com/read/28543773/degradation-of-heme-oxygenase-1-by-the-immunoproteasome-in-astrocytes-a-potential-interferon-%C3%AE-dependent-mechanism-contributing-to-hiv-neuropathogenesis
#1
Colleen E Kovacsics, Alexander J Gill, Surendra S Ambegaokar, Benjamin B Gelman, Dennis L Kolson
Induction of the detoxifying enzyme heme oxygenase-1 (HO-1) is a critical protective host response to cellular injury associated with inflammation and oxidative stress. We previously found that HO-1 protein expression is reduced in brains of HIV-infected individuals with HIV-associated neurocognitive disorders (HAND) and in HIV-infected macrophages, where this reduction associates with enhanced glutamate release and neurotoxicity. Because HIV-infected macrophages are a small component of the cellular content of the brain, the reduction of macrophage HO-1 expression likely accounts for a small portion of brain HO-1 loss in HIV infection...
May 22, 2017: Glia
https://www.readbyqxmd.com/read/28533442/the-role-of-shed-prp-c-in-the-neuropathogenesis-of-hiv-infection
#2
Bezawit W Megra, Eliseo A Eugenin, Joan W Berman
HIV-1 enters the CNS soon after peripheral infection and causes chronic neuroinflammation and neuronal damage that leads to cognitive impairment in 40-70% of HIV-infected people. The nonpathogenic cellular isoform of the human prion protein (PrP(c)) is an adhesion molecule constitutively expressed in the CNS. Previously, our laboratory showed that shed PrP(c) (sPrP(c)) is increased in the cerebrospinal fluid of HIV-infected people with cognitive deficits as compared with infected people with no impairment. In this article, we demonstrate that CCL2 and TNF-α, inflammatory mediators that are elevated in the CNS of HIV-infected people, increase shedding of PrP(c) from human astrocytes by increasing the active form of the metalloprotease ADAM10...
May 22, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28473642/selective-vulnerability-of-striatal-d2-versus-d1-dopamine-receptor-expressing-medium-spiny-neurons-in-hiv-1-tat-transgenic-male-mice
#3
Christina J Schier, William D Marks, Jason J Paris, Aaron J Barbour, Virginia D McLane, William F Maragos, A Rory McQuiston, Pamela E Knapp, Kurt F Hauser
Despite marked regional differences in HIV susceptibility within the CNS, there has been surprisingly little exploration into the differential vulnerability among neuron types and the circuits they underlie. The dorsal striatum is especially susceptible, harboring high viral loads and displaying marked neuropathology-with motor impairment a frequent manifestation of chronic infection; yet, little is known about the response of individual striatal neuron types to HIV or how this disrupts function. Consequently, we examined the morphological, electrophysiological, and anxiety-like and exploratory/locomotor behavioral effects of HIV-1 Tat in dopamine subtype 1 (D1) and dopamine subtype 2 (D2) receptor-expressing striatal medium spiny neurons (MSNs) by breeding transgenic Tat-expressing mice to Drd1a-tdTomato- or Drd2-eGFP- reporter mice...
May 4, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28368497/blood-brain-barrier-disruption-is-initiated-during-primary-hiv-infection-and-not-rapidly-altered-by-antiretroviral-therapy
#4
Elham Rahimy, Fang-Yong Li, Lars Hagberg, Dietmar Fuchs, Kevin Robertson, Dieter J Meyerhoff, Henrik Zetterberg, Richard W Price, Magnus Gisslén, Serena Spudich
Background: We explored the establishment of abnormal blood-brain barrier (BBB) permeability and its relationship to neuropathogenesis during primary human immunodeficiency virus (HIV) infection by evaluating the cerebrospinal fluid (CSF) to serum albumin quotient (QAlb) in patients with primary HIV infection. We also analyzed effects of initiating combination antiretroviral therapy (cART). Methods: The QAlb was measured in longitudinal observational studies of primary HIV infection...
April 1, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28358733/plasma-dickkopf-related-protein-1-an-antagonist-of-the-wnt-pathway-is-associated-with-hiv-associated-neurocognitive-impairment
#5
Chunjiang Yu, Melanie Seaton, Scott Letendre, Robert Heaton, Lena Al-Harthi
OBJECTIVE: DKK1 is a soluble antagonist of the Wnt pathway. It binds to and sequesters LRP5/6 away from Wnts. Because the Wnt pathway regulates synaptic transmission and plasticity, we hypothesized that increased DKK1 would increase the risk for neurocognitive impairment (NCI) in HIV+ individuals. We evaluated here the relationship between plasma DKK1 and global NCI. METHODS: Plasma samples and data from 41 HIV+ and 42 HIV- adults were obtained from the University of California, San Diego...
March 29, 2017: AIDS
https://www.readbyqxmd.com/read/28133717/dopamine-increases-cd14-cd16-monocyte-transmigration-across-the-blood-brain-barrier-implications-for-substance-abuse-and-hiv-neuropathogenesis
#6
Tina M Calderon, Dionna W Williams, Lillie Lopez, Eliseo A Eugenin, Laura Cheney, Peter J Gaskill, Mike Veenstra, Kathryn Anastos, Susan Morgello, Joan W Berman
In human immunodeficiency virus-1 (HIV) infected individuals, substance abuse may accelerate the development and/or increase the severity of HIV associated neurocognitive disorders (HAND). It is proposed that CD14(+)CD16(+) monocytes mediate HIV entry into the central nervous system (CNS) and that uninfected and infected CD14(+)CD16(+) monocyte transmigration across the blood brain barrier (BBB) contributes to the establishment and propagation of CNS HIV viral reservoirs and chronic neuroinflammation, important factors in the development of HAND...
June 2017: Journal of Neuroimmune Pharmacology: the Official Journal of the Society on NeuroImmune Pharmacology
https://www.readbyqxmd.com/read/28127697/differential-mechanisms-of-inflammation-and-endothelial-dysfunction-by-hiv-1-subtype-b-and-recombinant-crf02_ag-tat-proteins-on-human-brain-microvascular-endothelial-cells-implications-for-viral-neuropathogenesis
#7
Biju Bhargavan, Georgette D Kanmogne
The recombinant HIV-1 CRF02_AG is prevalent in West-Central Africa but its effects on the blood-brain barrier (BBB) and HIV-associated neurocognitive disorders (HAND) are not known. We analyzed the effects of Tat from HIV-1 subtype-B (Tat.B) and CRF02_AG (Tat.AG) on primary human brain microvascular endothelial cells (HBMEC), the major BBB component. Exposure of HBMEC to Tat.B increased IL-6 expression and transcription by 9- (P < 0.001) and 113-fold (P < 0.001), respectively, whereas Tat.AG increased IL-6 expression and transcription by 2...
January 27, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28046096/early-antiretroviral-therapy-is-associated-with-lower-hiv-dna-molecular-diversity-and-lower-inflammation-in-cerebrospinal-fluid-but-does-not-prevent-the-establishment-of-compartmentalized-hiv-dna-populations
#8
Michelli F Oliveira, Antoine Chaillon, Masato Nakazawa, Milenka Vargas, Scott L Letendre, Matthew C Strain, Ronald J Ellis, Sheldon Morris, Susan J Little, Davey M Smith, Sara Gianella
Even when antiretroviral therapy (ART) is started early after infection, HIV DNA might persist in the central nervous system (CNS), possibly contributing to inflammation, brain damage and neurocognitive impairment. Paired blood and cerebrospinal fluid (CSF) were collected from 16 HIV-infected individuals on suppressive ART: 9 participants started ART <4 months of the estimated date of infection (EDI) ("early ART"), and 7 participants started ART >14 months after EDI ("late ART"). For each participant, neurocognitive functioning was measured by Global Deficit Score (GDS)...
January 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28005686/transcriptome-analyses-identify-key-cellular-factors-associated-with-hiv-1-associated-neuropathogenesis-in-infected-men
#9
Narasimhan J Venkatachari, Siddhartha Jain, Leah Walker, Shalmali Bivalkar-Mehla, Ansuman Chattopadhyay, Ziv Bar-Joseph, Charles Rinaldo, Ann Ragin, Eric Seaberg, Andrew Levine, James Becker, Eileen Martin, Ned Sacktor, Velpandi Ayyavoo
OBJECTIVE: HIV-1 viral proteins and host inflammatory factors have a direct role in neuronal toxicity in vitro; however, the contribution of these factors in vivo in HIV-1-associated neurocognitive disorder (HAND) is not fully understood. We applied novel Systems Biology approaches to identify specific cellular and viral factors and their related pathways that are associated with different stages of HAND. DESIGN: A cross-sectional study of individuals enrolled in the Multicenter AIDS Cohort Study including HIV-1-seronegative (N = 36) and HIV-1-seropositive individuals without neurocognitive symptoms (N = 16) or with mild neurocognitive disorder (MND) (N = 8) or HIV-associated dementia (HAD) (N = 16)...
March 13, 2017: AIDS
https://www.readbyqxmd.com/read/27862491/alarmins-and-central-nervous-system-inflammation-in-hiv-associated-neurological-disorders
#10
REVIEW
M-L Gougeon
In the era of highly active antiretroviral therapy (HAART), HIV-1-associated neurocognitive disorders (HAND) persist in infected individuals with adequate immunological and virological status. Risk factors for cognitive impairment include hepatitis C virus co-infection, host genetic factors predisposing to HAND, the early establishment of the virus in the CNS and its persistence under HAART; thus, the CNS is an important reservoir for HIV. Microglial cells are permissive to HIV-1, and NLRP3 inflammasome-associated genes were found expressed in brains of HIV-1-infected persons, contributing to brain disease...
May 2017: Journal of Internal Medicine
https://www.readbyqxmd.com/read/27834864/chronic-binge-alcohol-administration-dysregulates-hippocampal-genes-involved-in-immunity-and-neurogenesis-in-simian-immunodeficiency-virus-infected-macaques
#11
John K Maxi, Matt Dean, Jovanny Zabaleta, Krzysztof Reiss, Gregory J Bagby, Steve Nelson, Peter J Winsauer, Francesca Peruzzi, Patricia E Molina
Alcohol use disorders (AUD) exacerbate neurocognitive dysfunction in Human Immunodeficiency Virus (HIV+) patients. We have shown that chronic binge alcohol (CBA) administration (13-14 g EtOH/kg/wk) prior to and during simian immunodeficiency virus (SIV) infection in rhesus macaques unmasks learning deficits in operant learning and memory tasks. The underlying mechanisms of neurocognitive alterations due to alcohol and SIV are not known. This exploratory study examined the CBA-induced differential expression of hippocampal genes in SIV-infected (CBA/SIV+; n = 2) macaques in contrast to those of sucrose administered, SIV-infected (SUC/SIV+; n = 2) macaques...
November 9, 2016: Biomolecules
https://www.readbyqxmd.com/read/27819802/immediate-initiation-of-cart-is-associated-with-lower-levels-of-cerebrospinal-fluid-ykl-40-a-marker-of-microglial-activation-in-hiv-1-infection
#12
Michael J Peluso, Victor Valcour, Nittaya Phanuphak, Jintanat Ananworanich, James L K Fletcher, Thep Chalermchai, Shelly J Krebs, Merlin L Robb, Joanna Hellmuth, Magnus Gisslén, Henrik Zetterberg, Serena Spudich
OBJECTIVE: To characterize cerebrospinal fluid (CSF) YKL-40, a unique biomarker that reflects activation of microglial cells, in acute (AHI) and chronic HIV-1 infection (CHI) and to determine the effect of treatment initiation on levels of this marker. DESIGN: A cross-sectional study of two groups of HIV-infected participants at baseline and follow-up timepoints. METHODS: AHI (n = 33) and CHI (n = 34) participants underwent CSF and blood sampling before treatment initiation with combination antiretroviral therapy (cART) and at follow-up on cART in a subset of these individuals [6 months in AHI participants (n = 24), 1 year in CHI participants (n = 10)]...
January 14, 2017: AIDS
https://www.readbyqxmd.com/read/27761954/novel-insights-into-role-of-mir-320a-vdac1-axis-in-astrocyte-mediated-neuronal-damage-in-neuroaids
#13
Mahar Fatima, Bharat Prajapati, Kanza Saleem, Rina Kumari, Chitra Mohindar Singh Singal, Pankaj Seth
Astroglia are indispensable component of the tripartite synapse ensheathing innumerous soma and synapses. Its proximity to neurons aids the regulation of neuronal functions, health and survival through dynamic neuroglia crosstalk. Susceptibility of astrocyte to HIV-1 infection and subsequent latency culminates in compromised neuronal health. The viral protein HIV-1 transactivator of transcription (Tat) is neurotoxic. HIV-1 Tat is detected in brain of AIDS patients even in cases where viral load is non-detectable due to successful HAART therapy...
February 2017: Glia
https://www.readbyqxmd.com/read/27686675/progressive-multifocal-leukoencephalopathy-in-hiv-uninfected-individuals
#14
REVIEW
Deanna Saylor, Arun Venkatesan
Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system (CNS) caused by the human neurotropic polyomavirus JC (JCV). The disease occurs virtually exclusively in immunocompromised individuals, and, prior to the introduction of antiretroviral therapy, was seen most commonly in the setting of HIV/AIDS. More recently, however, the incidence of PML in HIV-uninfected persons has increased with broader use of immunosuppressive and immunomodulatory medications utilized in a variety of systemic and neurologic autoimmune disorders...
November 2016: Current Infectious Disease Reports
https://www.readbyqxmd.com/read/27668463/modeling-the-effects-of-morphine-on-simian-immunodeficiency-virus-dynamics
#15
Naveen K Vaidya, Ruy M Ribeiro, Alan S Perelson, Anil Kumar
Complications of HIV-1 infection in individuals who utilize drugs of abuse is a significant problem, because these drugs have been associated with higher virus replication and accelerated disease progression as well as severe neuropathogenesis. To gain further insight it is important to quantify the effects of drugs of abuse on HIV-1 infection dynamics. Here, we develop a mathematical model that incorporates experimentally observed effects of morphine on inducing HIV-1 co-receptor expression. For comparison we also considered viral dynamic models with cytolytic or noncytolytic effector cell responses...
September 2016: PLoS Computational Biology
https://www.readbyqxmd.com/read/27629381/comparative-dna-methylation-profiling-reveals-an-immunoepigenetic-signature-of-hiv-related-cognitive-impairment
#16
Michael J Corley, Christian Dye, Michelle L D'Antoni, Mary Margaret Byron, Kaahukane Leite-Ah Yo, Annette Lum-Jones, Beau Nakamoto, Victor Valcour, Ivo SahBandar, Cecilia M Shikuma, Lishomwa C Ndhlovu, Alika K Maunakea
Monocytes/macrophages contribute to the neuropathogenesis of HIV-related cognitive impairment (CI); however, considerable gaps in our understanding of the precise mechanisms driving this relationship remain. Furthermore, whether a distinct biological profile associated with HIV-related CI resides in immune cell populations remains unknown. Here, we profiled DNA methylomes and transcriptomes of monocytes derived from HIV-infected individuals with and without CI using genome-wide DNA methylation and gene expression profiling...
September 15, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27544476/non-human-primate-models-of-siv-infection-and-cns-neuropathology
#17
REVIEW
Kenneth Williams, Andrew Lackner, Jaclyn Mallard
Non-human primate models of AIDS and neuroAIDS are the premiere model of HIV infection of the CNS and neuropathogenesis. This review discusses current SIV infection models of neuroAIDS emphasizing findings in the last two years. Consistent in these findings is the interplay between host factors that regulate immune responses to virus and viral replication. Several rapid models of AIDS with consistent CNS pathogenesis exist, each of which modulates by antibody treatment or viruses that cause rapid immune suppression and replicate well in macrophages...
August 2016: Current Opinion in Virology
https://www.readbyqxmd.com/read/27535703/hiv-and-cocaine-impact-glial-metabolism-energy-sensor-amp-activated-protein-kinase-role-in-mitochondrial-biogenesis-and-epigenetic-remodeling
#18
Thangavel Samikkannu, Venkata S R Atluri, Madhavan P N Nair
HIV infection and cocaine use have been identified as risk factors for triggering neuronal dysfunction. In the central nervous system (CNS), energy resource and metabolic function are regulated by astroglia. Glia is the major reservoir of HIV infection and disease progression in CNS. However, the role of cocaine in accelerating HIV associated energy deficit and its impact on neuronal dysfunction has not been elucidated yet. The aim of this study is to elucidate the molecular mechanism of HIV associated neuropathogenesis in cocaine abuse and how it accelerates the energy sensor AMPKs and its subsequent effect on mitochondrial oxidative phosphorylation (OXPHOS), BRSKs, CDC25B/C, MAP/Tau, Wee1 and epigenetics remodeling complex SWI/SNF...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27400931/specific-amino-acids-in-hiv-1-vpr-are-significantly-associated-with-differences-in-patient-neurocognitive-status
#19
Will Dampier, Gregory C Antell, Benjamas Aiamkitsumrit, Michael R Nonnemacher, Jeffrey M Jacobson, Vanessa Pirrone, Wen Zhong, Katherine Kercher, Shendra Passic, Jean W Williams, Tony James, Kathryn N Devlin, Tania Giovannetti, David J Libon, Zsofia Szep, Garth D Ehrlich, Brian Wigdahl, Fred C Krebs
Even in the era of combination antiretroviral therapies used to combat human immunodeficiency virus type 1 (HIV-1) infection, up to 50 % of well-suppressed HIV-1-infected patients are still diagnosed with mild neurological deficits referred to as HIV-associated neurocognitive disorders (HAND). The multifactorial nature of HAND likely involves the HIV-1 accessory protein viral protein R (Vpr) as an agent of neuropathogenesis. To investigate the effect of naturally occurring variations in Vpr on HAND in well-suppressed HIV-1-infected patients, bioinformatic analyses were used to correlate peripheral blood-derived Vpr sequences with patient neurocognitive performance, as measured by comprehensive neuropsychological assessment and the resulting Global Deficit Score (GDS)...
February 2017: Journal of Neurovirology
https://www.readbyqxmd.com/read/27326669/combined-chronic-blockade-of-hyper-active-l-type-calcium-channels-and-nmda-receptors-ameliorates-hiv-1-associated-hyper-excitability-of-mpfc-pyramidal-neurons
#20
Christina E Khodr, Lihua Chen, Sonya Dave, Lena Al-Harthi, Xiu-Ti Hu
Human Immunodeficiency Virus type 1 (HIV-1) infection induces neurological and neuropsychological deficits, which are associated with dysregulation of the medial prefrontal cortex (mPFC) and other vulnerable brain regions. We evaluated the impact of HIV infection in the mPFC and the therapeutic potential of targeting over-active voltage-gated L-type Ca(2+) channels (L-channel) and NMDA receptors (NMDAR), as modeled in HIV-1 transgenic (Tg) rats. Whole-cell patch-clamp recording was used to assess the membrane properties and voltage-sensitive Ca(2+) potentials (Ca(2+) influx) in mPFC pyramidal neurons...
October 2016: Neurobiology of Disease
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