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HIV Neuropathogenesis

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https://www.readbyqxmd.com/read/29128906/toll-like-receptor-3-mediates-hiv-1-induced-interleukin-6-expression-in-the-human-brain-endothelium-via-tak1-and-jnk-pathways-implications-for-viral-neuropathogenesis
#1
Biju Bhargavan, Georgette D Kanmogne
HIV-1-associated neurocognitive disorders (HAND) is associated with blood-brain-barrier (BBB) inflammation, and inflammation involves toll-like receptors (TLRs) signaling. It is not known whether primary human brain microvascular endothelial cells (HBMEC), the major BBB component, express TLRs or whether TLRs are involved in BBB dysfunction and HAND. We demonstrate that HBMEC express TLR3, 4, 5, 7, 9, and 10, and TLR3 was the most abundant. HIV-1 and TLR3 activation increased endothelial TLR3 transcription and expression...
November 11, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/29058550/immunomodulatory-role-of-complement-proteins-in-the-neuropathology-associated-with-opiate-abuse-and-hiv-1-co-morbidity
#2
Supriya D Mahajan, Ravikumar Aalinkeel, Neil U Parikh, Alexander Jacob, Katherine Cwiklinski, Prateet Sandhu, Kevin Le, Alexander W Loftus, Stanley A Schwartz, Richard J Quigg, Jessy J Alexander
The complement system which is a critical mediator of innate immunity plays diverse roles in the neuropathogenesis of HIV-1 infection such as clearing HIV-1 and promoting productive HIV-1 replication. In the development of HIV-1 associated neurological disorders (HAND), there may be an imbalance between complement activation and regulation, which may contribute to the neuronal damage as a consequence of HIV-1 infection. It is well recognized that opiate abuse exacerbates HIV-1 neuropathology, however, little is known about the role of complement proteins in opiate induced neuromodulation, specifically in the presence of co-morbidity such as HIV-1 infection...
November 2017: Immunological Investigations
https://www.readbyqxmd.com/read/29056673/feline-immunodeficiency-virus-neuropathogenesis-a-model-for-hiv-induced-cns-inflammation-and-neurodegeneration
#3
REVIEW
Rick B Meeker, Lola Hudson
Feline Immunodeficiency virus (FIV), similar to its human analog human immunodeficiency virus (HIV), enters the central nervous system (CNS) soon after infection and establishes a protected viral reservoir. The ensuing inflammation and damage give rise to varying degrees of cognitive decline collectively known as HIV-associated neurocognitive disorders (HAND). Because of the similarities to HIV infection and disease, FIV has provided a useful model for both in vitro and in vivo studies of CNS infection, inflammation and pathology...
March 6, 2017: Veterinary Sciences
https://www.readbyqxmd.com/read/28978127/hiv-1-gp120-clade-b-c-induces-a-grp78-driven-cytoprotective-mechanism-in-astrocytoma
#4
Sheila N López, Madeline Rodríguez-Valentín, Mariela Rivera, Maridaliz Rodríguez, Mohan Babu, Luis A Cubano, Huangui Xiong, Guangdi Wang, Lilia Kucheryavykh, Nawal M Boukli
HIV-1 clades are known to be one of the key factors implicated in modulating HIV-associated neurocognitive disorders. HIV-1 B and C clades account for the majority of HIV-1 infections, clade B being the most neuropathogenic. The mechanisms behind HIV-mediated neuropathogenesis remain the subject of active research. We hypothesized that HIV-1 gp120 clade B and C proteins may exert differential proliferation, cell survival and NeuroAIDS effects in human astrocytoma cells via the Unfolded Protein Response, an endoplasmic reticulum- based cytoprotective mechanism...
September 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28975505/an-siv-macaque-model-targeted-to-study-hiv-associated-neurocognitive-disorders
#5
REVIEW
Sarah E Beck, Suzanne E Queen, Kelly A Metcalf Pate, Lisa M Mangus, Celina M Abreu, Lucio Gama, Kenneth W Witwer, Robert J Adams, M Christine Zink, Janice E Clements, Joseph L Mankowski
Simian immunodeficiency virus (SIV) infection of pigtailed macaques is a highly representative and well-characterized animal model for HIV neuropathogenesis studies that provides an excellent opportunity to study and develop prognostic markers of HIV-associated neurocognitive disorders (HAND) for HIV-infected individuals. SIV studies can be performed in a controlled setting that enhances reproducibility and offers high-translational value. Similar to observations in HIV-infected patients receiving antiretroviral therapy (ART), ongoing neurodegeneration and inflammation are present in SIV-infected pigtailed macaques treated with suppressive ART...
October 3, 2017: Journal of Neurovirology
https://www.readbyqxmd.com/read/28886986/role-of-connexin-and-pannexin-containing-channels-in-hiv-infection-and-neuroaids
#6
REVIEW
Shaily Malik, Eliseo A Eugenin
Neuron-Glia crosstalk is essential for efficient synaptic communication, cell growth and differentiation, neuronal activity, neurotransmitter recycling, and brain immune response. The master regulators of this neuron-glia communication are connexin containing Gap Junctions (GJs) and Hemichannels (HCs) as well as pannexin HCs. However, the role of these channels under pathological conditions, especially in infectious diseases is still in exploratory stages. Human Immunodeficiency Virus-1 (HIV) is one such infectious agent that takes advantage of the host intercellular communication systems, GJs and HCs, to exacerbate viral pathogenesis in the brain in spite of the antiretroviral therapy effectively controlling viral replication in the periphery...
September 5, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28870557/retroviral-envelope-proteins-involvement-in-neuropathogenesis
#7
REVIEW
Dorte Tranberg Hansen, Thor Petersen, Tove Christensen
The primary disease caused by infection with the exogenous human retroviruses, human immunodeficiency virus 1 (HIV-1) or human T-cell lymphotropic virus 1 (HTLV-1), may overlay manifestations of additional autoimmune pathogenesis. Currently, a role for human endogenous retroviruses (HERVs) is also emerging in some autoimmune/immune-mediated diseases, particularly in multiple sclerosis (MS). Both exogenous and endogenous retroviruses have the potential to elicit the processes leading to autoimmune disease. The pathogenicity of the retroviral envelope protein (Env) is a key player with notable importance in neuroimmune diseases...
September 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28866957/nanocarriers-for-brain-specific-delivery-of-anti-retro-viral-drugs-challenges-and-achievements
#8
Nila Mary Varghese, Senthil Venkatachalam, Shailendra K Saxena
HIV/AIDS is a global pandemic and the deleterious effects of Human Immunodeficiency Virus in the brain cannot be overlooked. Though the current Anti-Retro Viral therapy is able to reduce the virus load in the peripheral tissues of the body, the inability of the anti-retro viral drugs to cross the Blood Brain Barrier, as such, limits its therapeutic effect in the brain. The development of newer, successful nanoparticulate drug delivery systems to enhance the feasibility of the anti-retro viral drugs to the brain, offers a novel strategy to treat the AIDS related neuronal degradation...
September 4, 2017: Journal of Drug Targeting
https://www.readbyqxmd.com/read/28864545/first-person-luca-sardo
#9
(no author information available yet)
First Person is a series of interviews with the first authors of a selection of papers published in Journal of Cell Science, helping early-career researchers promote themselves alongside their papers. Luca Sardo is co-first author on 'Real-time visualization of chromatin modification in isolated nuclei', published in Journal of Cell Science. Dr Sardo is a Postdoctoral Fellow at the Department of Biological Sciences, University of the Sciences in Philadelphia, investigating the mechanisms of HIV neuropathogenesis and latency...
September 1, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28792504/common-gene-network-signature-of-different-neurological-disorders-and-their-potential-implications-to-neuroaids
#10
Vidya Sagar, S Pilakka-Kanthikeel, Paola C Martinez, V S R Atluri, M Nair
The neurological complications of AIDS (neuroAIDS) during the infection of human immunodeficiency virus (HIV) are symptomized by non-specific, multifaceted neurological conditions and therefore, defining a specific diagnosis/treatment mechanism(s) for this neuro-complexity at the molecular level remains elusive. Using an in silico based integrated gene network analysis we discovered that HIV infection shares convergent gene networks with each of twelve neurological disorders selected in this study. Importantly, a common gene network was identified among HIV infection, Alzheimer's disease, Parkinson's disease, multiple sclerosis, and age macular degeneration...
2017: PloS One
https://www.readbyqxmd.com/read/28640909/hiv-tat-regulates-macrophage-gene-expression-in-the-context-of-neuroaids
#11
Loreto Carvallo, Lillie Lopez, Jorge E Fajardo, Matias Jaureguiberry-Bravo, Andras Fiser, Joan W Berman
Despite the success of cART, greater than 50% of HIV infected people develop cognitive and motor deficits termed HIV-associated neurocognitive disorders (HAND). Macrophages are the major cell type infected in the CNS. Unlike for T cells, the virus does not kill macrophages and these long-lived cells may become HIV reservoirs in the brain. They produce cytokines/chemokines and viral proteins that promote inflammation and neuronal damage, playing a key role in HIV neuropathogenesis. HIV Tat is the transactivator of transcription that is essential for replication and transcriptional regulation of the virus and is the first protein to be produced after HIV infection...
2017: PloS One
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
#12
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...
August 2017: Glia
https://www.readbyqxmd.com/read/28533442/the-role-of-shed-prp-c-in-the-neuropathogenesis-of-hiv-infection
#13
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...
July 1, 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
#14
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. However, little is known about the response of individual striatal neuron types to HIV or how this disrupts function. Therefore, we investigated the morphological and electrophysiological effects of HIV-1 trans-activator of transcription (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...
June 7, 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
#15
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
#16
Chunjiang Yu, Melanie Seaton, Scott Letendre, Robert Heaton, Lena Al-Harthi
OBJECTIVE: Dickkopf-related protein 1 (DKK1) is a soluble antagonist of the Wningless (Wnt) pathway. It binds to and sequesters low-density lipoprotein receptor-related proteins 5/6 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-positive (HIV) individuals. We evaluated, here, the relationship between plasma DKK1 and global NCI. METHODS: Plasma samples and data from 41 HIV to 42 HIV adults were obtained from the University of California, San Diego, California, USA...
June 19, 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
#17
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
#18
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
#19
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
#20
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
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