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https://www.readbyqxmd.com/read/28107387/neuronal-cell-death-and-degeneration-through-increased-nitroxidative-stress-and-tau-phosphorylation-in-hiv-1-transgenic-rats
#1
Young-Eun Cho, Myoung-Hwa Lee, Byoung-Joon Song
The underlying mechanisms for increased neurodegeneration and neurocognitive deficits in HIV-infected people are unclear. Therefore, this study was aimed to investigate the mechanisms of increased neurodegeneration in 5-month old male HIV-1 Transgenic (Tg) rats compared to the age- and gender-matched wild-type (WT) by evaluating histological changes and biochemical parameters of the key proteins involved in the cell death signaling and apoptosis. Histological and immunohistochemical analyses revealed decreased neuronal cells with elevated astrogliosis in HIV-1 Tg rats compared to WT...
2017: PloS One
https://www.readbyqxmd.com/read/28105557/the-anticancer-drug-sunitinib-promotes-autophagyand-protects-from-neurotoxicity-in-an-hiv-1-tat-model-of-neurodegeneration
#2
Jerel A Fields, Jeff Metcalf, Cassia Overk, Anthony Adame, Brian Spencer, Wolfgang Wrasidlo, Jazmin Florio, Edward Rockenstein, Johnny J He, Eliezer Masliah
Despite the success of antiretroviral therapies to control systemic HIV-1 infection, the prevalence of HIV-associated neurocognitive disorders (HANDs) has not decreased among aging patients with HIV. Autophagy pathway alterations, triggered by HIV-1 proteins including gp120, Tat, and Nef, might contribute to the neurodegenerative process in aging patients with HAND. Although no treatments are currently available to manage HAND, we have previously shown that sunitinib, an anticancer drug that blocks receptor tyrosine-kinase and cyclin kinase pathways, might be of interest...
January 19, 2017: Journal of Neurovirology
https://www.readbyqxmd.com/read/28102671/structural-analysis-of-glycosylated-intact-hiv-1-gp120-b12-antibody-complex-using-hydroxyl-radical-protein-footprinting
#3
Xiaoyan Li, Oliver C Grant, Keigo Ito, Aaron Wallace, Shixia Wang, Peng Zhao, Lance Wells, Shan Lu, Robert J Woods, Joshua S Sharp
Glycoprotein gp120 is a surface antigen and virulence factor of the human immunodeficiency virus-1 (HIV-1). Broadly neutralizing antibodies (bNAbs) that are reactive to gp120 from a variety of HIV isolates offer hope for the development of broadly effective immunogens for vaccination purposes, if the interactions between gp120 and bNAbs can be understood. From a structural perspective, gp120 is a particularly difficult system due to its size, the presence of multiple flexible regions, and the large amount of glycosylation, all of which are important in gp120-bNAb interactions...
January 19, 2017: Biochemistry
https://www.readbyqxmd.com/read/28100618/influence-of-the-envelope-gp120-phe-43-cavity-on-hiv-1-sensitivity-to-adcc-responses
#4
Jérémie Prévost, Daria Zoubchenok, Jonathan Richard, Maxime Veillette, Beatriz Pacheco, Mathieu Coutu, Nathalie Brassard, Matthew S Parsons, Kiat Ruxrungtham, Torsak Bunupuradah, Sodsai Tovanabutra, Kwan-Ki Hwang, M Anthony Moody, Barton F Haynes, Mattia Bonsignori, Joseph Sodroski, Daniel E Kaufmann, George M Shaw, Agnès L Chenine, Andrés Finzi
: HIV-1-infected cells presenting envelope glycoproteins (Env) in the CD4-bound conformation on their surface are preferentially targeted by antibody-dependent cellular-mediated cytotoxicity (ADCC). HIV-1 has evolved sophisticated mechanisms to avoid exposure of Env ADCC epitopes by downregulating CD4 and by limiting the overall amount of Env on the cell surface. In HIV-1, substitution of large residues such as histidine or tryptophan for serine 375 (S375H/W) in the gp120 Phe 43 cavity, where Phe 43 of CD4 contacts gp120, results in the spontaneous sampling of an Env conformation closer to CD4-bound state...
January 18, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28097000/biased-small-molecule-ligands-for-selective-inhibition-of-hiv-1-cell-entry-via-ccr5
#5
Christian Berg, Katja Spiess, Hans R Lüttichau, Mette M Rosenkilde
Since the discovery of HIV's use of CCR5 as the primary coreceptor in fusion, the focus on developing small-molecule receptor antagonists for inhibition hereof has only resulted in one single drug, Maraviroc. We therefore investigated the possibility of using small-molecule CCR5 agonists as HIV-1 fusion inhibitors. A virus-free cell-based fusion reporter assay, based on mixing "effector cells" (expressing HIV Env and luciferase activator) with "target cells" (expressing CD4, CCR5 wild type or a selection of well-described mutations, and luciferase reporter), was used as fusion readout...
December 2016: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/28094765/selective-antagonism-of-muscarinic-receptors-is-neuroprotective-in-peripheral-neuropathy
#6
Nigel A Calcutt, Darrell R Smith, Katie Frizzi, Mohammad Golam Sabbir, Subir K Roy Chowdhury, Teresa Mixcoatl-Zecuatl, Ali Saleh, Nabeel Muttalib, Randy Van der Ploeg, Joseline Ochoa, Allison Gopaul, Lori Tessler, Jürgen Wess, Corinne G Jolivalt, Paul Fernyhough
Sensory neurons have the capacity to produce, release, and respond to acetylcholine (ACh), but the functional role of cholinergic systems in adult mammalian peripheral sensory nerves has not been established. Here, we have reported that neurite outgrowth from adult sensory neurons that were maintained under subsaturating neurotrophic factor conditions operates under cholinergic constraint that is mediated by muscarinic receptor-dependent regulation of mitochondrial function via AMPK. Sensory neurons from mice lacking the muscarinic ACh type 1 receptor (M1R) exhibited enhanced neurite outgrowth, confirming the role of M1R in tonic suppression of axonal plasticity...
January 17, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28093272/a-method-for-obtaining-simian-immunodeficiency-virus-rna-sequences-from-laser-capture-microdissected-and-immune-captured-cd68-and-cd163-macrophages-from-frozen-tissue-sections-of-bone-marrow-and-brain
#7
Jaclyn Mallard, Emily Papazian, Caroline Soulas, David J Nolan, Marco Salemi, Kenneth C Williams
Laser capture microdissection (LCM) is used to extract cells or tissue regions for analysis of RNA, DNA or protein. Several methods of LCM are established for different applications, but a protocol for consistently obtaining lentiviral RNA from LCM captured immune cell populations is not described. Obtaining optimal viral RNA for analysis of viral genes from immune-captured cells using immunohistochemistry (IHC) and LCM is challenging. IHC protocols have long antibody incubation times that increase risk of RNA degradation...
January 13, 2017: Journal of Immunological Methods
https://www.readbyqxmd.com/read/28076686/small-molecule-hiv-1-entry-inhibitors-targeting-gp120-and-gp41-a-patent-review-2010-2015
#8
Wen Li, Lu Lu, Weihua Li, Shibo Jiang
It is essential to discover and develop small-molecule HIV-1 entry inhibitors with suitable pharmaceutical properties. Areas covered: We review the development of small-molecule HIV-1 entry inhibitors as evidenced in patents, patent applications, and related research articles published between 2010 and 2015. Expert opinion: HIV-1 Env gp120 and gp41 are important targets for development of HIV-1 entry inhibitors. The Phe43 pocket in gp120 and the highly conserved hydrophobic pocket on gp41 NHR-trimer are important targets for identification of HIV-1 attachment and fusion inhibitors, respectively...
January 19, 2017: Expert Opinion on Therapeutic Patents
https://www.readbyqxmd.com/read/28076415/structure-and-recognition-of-a-novel-hiv-1-gp120-gp41-interface-antibody-that-caused-mper-exposure-through-viral-escape
#9
Constantinos Kurt Wibmer, Jason Gorman, Gabriel Ozorowski, Jinal N Bhiman, Daniel J Sheward, Debra H Elliott, Julie Rouelle, Ashley Smira, M Gordon Joyce, Nonkululeko Ndabambi, Aliaksandr Druz, Mangai Asokan, Dennis R Burton, Mark Connors, Salim S Abdool Karim, John R Mascola, James E Robinson, Andrew B Ward, Carolyn Williamson, Peter D Kwong, Lynn Morris, Penny L Moore
A comprehensive understanding of the regions on HIV-1 envelope trimers targeted by broadly neutralizing antibodies may contribute to rational design of an HIV-1 vaccine. We previously identified a participant in the CAPRISA cohort, CAP248, who developed trimer-specific antibodies capable of neutralizing 60% of heterologous viruses at three years post-infection. Here, we report the isolation by B cell culture of monoclonal antibody CAP248-2B, which targets a novel membrane proximal epitope including elements of gp120 and gp41...
January 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28075174/analysis-of-sivmac-envelope-specific-antibodies-selected-via-phage-display
#10
Sergio Ita, Mayara Rovariz Agostinho, Katherine Sullivan, Seung Yub Han, Rana Akleh, Welkin Johnson, Ismael Ben Farouck Fofana
We have constructed a single chain Fv (scFv) phage display library from an SIV-infected rhesus macaque that developed unusually high-titer neutralizing antibody responses against tier-3, neutralization-resistant SIVmac239. The library was screened using trimeric (gp140) and monomeric (gp120) forms of the SIVmac239 envelope (Env) glycoprotein. We also cloned variable-heavy and variable-light (VH-VL) antibody fragments from 7 previously described rhesus macaque B-cell lines (BLCL) that produce SIV gp120-specific monoclonal antibodies (mAbs)...
January 11, 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/28074940/alpha7-nicotinic-acetylcholine-receptor-is-required-for-amyloid-pathology-in-brain-endothelial-cells-induced-by-glycoprotein-120-methamphetamine-and-nicotine
#11
Liqun Liu, Jingyi Yu, Li Li, Bao Zhang, Lingjuan Liu, Chun-Hua Wu, Ambrose Jong, Ding-An Mao, Sheng-He Huang
One of the most challenging issues in HIV-associated neurocognitive disorders (HAND) caused by HIV-1 virotoxins and drug abuse is the lack of understanding the underlying mechanisms that are commonly associated with disorders of the blood-brain barrier (BBB), which mainly consists of brain microvascular endothelial cells (BMEC). Here, we hypothesized that Glycoprotein 120 (gp120), methamphetamine (METH) and nicotine (NT) can enhance amyloid-beta (Aβ) accumulation in BMEC through Alpha7 nicotinic acetylcholine receptor (α7 nAChR)...
January 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28065732/a317491-relieved-hiv-gp120-associated-neuropathic-pain-involved-in-p2x3-receptor-in-dorsal-root-ganglia
#12
Zhihua Yi, Shenqiang Rao, Shuai Ouyang, Yi Bai, Jinpu Yang, Yucheng Ma, Xinyao Han, Bing Wu, Lifang Zou, Tianyu Jia, Shanhong Zhao, Xiaju Hu, Qiongqiong Lei, Yun Gao, Shuangmei Liu, Hong Xu, Chunping Zhang, Shangdong Liang, Guilin Li
Glycoprotein 120 (gp120) is an HIV envelope glycoprotein. Gp120 can directly stimulate the primary sensory afferent neurons and cause hyperalgesia. The P2X3 receptor in dorsal root ganglia (DRG) is involved in the transmission of pain. In this study, we aimed to explore the role of the P2X3 receptor in gp120-induced neuropathic pain. Our data showed that mechanical and thermal hyperalgesia in rats treated with gp120 were increased compared to those in the control group. The expression levels of the P2X3 mRNA and protein in rats treated with gp120 were higher than those in the control group...
January 5, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/28060015/ifn-%C3%AE-augments-nk-mediated-antibody-dependent-cellular-cytotoxicity-adcc-of-hiv-1-infected-autologous-cd4-t-cells-regardless-of-mhc-i-downregulation
#13
Costin Tomescu, Pablo Tebas, Luis J Montaner
DESIGN: We have previously shown that IFN-α stimulation augments direct NK cell lysis of autologous CD4 primary T cells infected with certain HIV-1 isolates based upon MHC-I downregulation capacity. Here, we investigated if Antibody Dependent Cellular Cytotoxicity (ADCC) could trigger lysis of HIV-1 isolates that were resistant to direct NK lysis and if IFN-α pre-stimulation of NK cells could further enhance ADCC. METHODS: Using broadly neutralizing monoclonal antibodies against gp120 (VRC01 or PGV04) or plasma from HIV-1 infected subjects (ART-suppressed or Elite Controller) to trigger ADCC, we measured NK cell chromium release cytotoxicity against HIV-1 infected autologous CD4 primary T cells and NK cell CD107a degranulation against gp120-coated CD4 T cells...
January 4, 2017: AIDS
https://www.readbyqxmd.com/read/28056499/recognition-of-hiv-inactivating-peptide-triazoles-by-the-recombinant-soluble-env-trimer-bg505-sosip-664
#14
Kriti Acharya, Adel A Rashad, Francesca Moraca, Per Johan Klasse, John P Moore, Cameron Abrams, Irwin Chaiken
Peptide triazole (PT) antagonists interact with gp120 subunits of HIV-1 Env trimers to block host cell receptor interactions, trigger gp120 shedding, irreversibly inactivate virus and inhibit infection. Despite these enticing functions, understanding the structural mechanism of PT-Env trimer encounter has been limited. In this work, we combined competition interaction analysis and computational simulation to demonstrate PT binding to the recombinant soluble trimer, BG505 SOSIP.664, a stable variant that resembles native virus spikes in binding to CD4 receptor as well as known conformationally-dependent Env antibodies...
January 5, 2017: Proteins
https://www.readbyqxmd.com/read/28051320/correlation-of-antibody-responses-to-a-peptide-antigen-gp120-c5-sup-501-512-sup-gp41-sup-732-744-sup-with-hiv-disease-progression
#15
Birger Sørensen, Maja A Sommerfelt, Grete Stjernholm, Peter Lawrence Smith, Mats Ökvist, Arnt-Ove Hovden, Gunnar Hoddevik, Robert R Redfield, Valentina Ustina, Øyvind Jelmert, Jerome Zeldis, Angus Dalgleish
Antibodies to the carboxyterminal constant (C5) region 5 of the HIV-1 envelope glycoprotein gp120 have previously been associated with slow disease progression. This is one of the regions on gp120 that interact with the transmembrane glycoprotein, gp41, anchoring it to the viral and infected cell membrane. This study analyzed humoral responses to a novel heterodimeric peptide construct comprising the C5<sup>501-512</sup> region and a compatible region on gp41<sup>732-744</sup>. Antibody prevalence to C5<sup>501-512</sup>/gp41<sup>732-744</sup> was associated with slow disease progression in a treatment naive historical longitudinal cohort from Norway (n=32; p=0...
January 4, 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/28050723/computational-identification-of-novel-entry-inhibitor-scaffolds-mimicking-primary-receptor-cd4-of-hiv-1-gp120
#16
Alexander M Andrianov, Ivan A Kashyn, Alexander V Tuzikov
Virtual screening of novel entry inhibitor scaffolds mimicking primary receptor CD4 of HIV-1 gp120 was carried out in conjunction with evaluation of their potential inhibitory activity by molecular modeling. To do this, pharmacophore models presenting different sets of the hotspots of cellular receptor CD4 for its interaction with gp120 were generated. These models were used as the templates for identification of CD4-mimetic candidates by the pepMMsMIMIC screening platform. Complexes of these candidates with gp120 were built by high-throughput ligand docking and their stability was estimated by molecular dynamics simulations and binding free energy calculations...
January 2017: Journal of Molecular Modeling
https://www.readbyqxmd.com/read/28027665/three-year-durability-of-immune-responses-induced-by-hiv-dna-and-hiv-modified-vaccinia-virus-ankara-and-effect-of-a-late-hiv-mva-boost-in-tanzanian-volunteers
#17
Agricola Joachim, Patricia J Munseri, Charlotta Nilsson, Muhammad Bakari, Said Aboud, Eligius F Lyamuya, Teghesti Tecleab, Valentina Liakina, Gabriella Scarlatti, Merlin Robb, Patricia Earl, Bernard Moss, Britta Wahren, Fred Mhalu, Guido Ferarri, Eric Sandström, Gunnel Biberfeld
We explored the duration of immune responses and the effect of a late third HIV-modified vaccinia virus Ankara (MVA) boost in HIV-DNA primed and HIV-MVA boosted Tanzanian volunteers. Twenty volunteers who had previously received three HIV-DNA and two HIV-MVA immunizations were given a third HIV-MVA immunization three years after the second HIV-MVA boost. At the time of the third HIV-MVA, 90% of the vaccinees had antibodies to HIV-1 subtype C gp140 (median titer 200) and 85% to subtype B gp160 (median titer 100)...
December 27, 2016: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/28011932/immunodominance-of-antibody-recognition-of-the-hiv-envelope-v2-region-in-ig-humanized-mice
#18
Kevin Wiehe, Nathan I Nicely, Bradley Lockwood, Masayuki Kuraoka, Kara Anasti, Sabrina Arora, Cindy M Bowman, Christina Stolarchuk, Robert Parks, Krissey E Lloyd, Shi-Mao Xia, Ryan Duffy, Xiaoying Shen, Christos A Kyratsous, Lynn E Macdonald, Andrew J Murphy, Richard M Scearce, M Anthony Moody, S Munir Alam, Laurent Verkoczy, Georgia D Tomaras, Garnett Kelsoe, Barton F Haynes
In the RV144 gp120 HIV vaccine trial, decreased transmission risk was correlated with Abs that reacted with a linear epitope at a lysine residue at position 169 (K169) in the HIV-1 envelope (Env) V2 region. The K169 V2 response was restricted to Abs bearing Vλ rearrangements that expressed aspartic acid/glutamic acid in CDR L2. The AE.A244 gp120 in AIDSVAX B/E also bound to the unmutated ancestor of a V2-glycan broadly neutralizing Ab, but this Ab type was not induced in the RV144 trial. In this study, we sought to determine whether immunodominance of the V2 linear epitope could be overcome in the absence of human Vλ rearrangements...
December 23, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28006952/comparison-of-antibody-responses-induced-by-rv144-vax003-and-vax004-vaccination-regimens
#19
Chitraporn Karnasuta, Siriwat Akapirat, Sirinan Madnote, Hathairat Savadsuk, Jiraporn Puangkaew, Surawach Rittiroongrad, Supachai Rerks-Ngarm, Sorachai Nitayaphan, Punnee Pitisuttithum, Jaranit Kaewkungwal, Jim Tartaglia, Faruk Sinangil, Donald P Francis, Merlin Robb, Mark de Souza, Nelson L Michael, Jean-Louis Excler, Jerome H Kim, Robert J O'Connell, Nicos Karasavvas
The RV144 prime-boost regimen demonstrated efficacy against HIV acquisition while VAX003 and VAX004 did not. Although these trials differed by risk groups, immunization regimens and immunogens, antibody responses may have contributed to the differences observed in vaccine efficacy. We assessed HIV-specific IgG, both total and subclass, and IgA binding to HIV envelope (Env): gp120 proteins and CycV2 and CycV3 peptides and gp70V1V2 scaffolds in these 3 HIV vaccine trials. After two protein immunizations, IgG responses to 92TH023 gp120 (contained in ALVAC-HIV vaccine) were significantly higher in RV144 but responses to other Env were higher in the VAX trials lacking ALVAC-HIV...
December 22, 2016: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/28005232/hiv-1-glycoprotein-120-enhancement-of-n-methyl-d-aspartate-nmda-receptor-mediated-excitatory-postsynaptic-currents-implications-for-hiv-1-associated-neural-injury
#20
Yan Zhou, Jianuo Liu, Huangui Xiong
It is widely accepted that human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein 120 (gp120) plays an important role in HIV-1-induced neural injury and pathogenesis of HIV-1-associated dementia (HAND). Multiple pathways have been proposed for gp120-induced neurotoxicity, amongst is the activation of N-Methyl-D-Aspartate receptors (NMDARs). It has been shown that gp120 causes neuronal injury or death and gp120 transgenic mice exhibit neurological similarity to that of HAND, all of which can be blocked or attenuated by NMDAR antagonists...
December 22, 2016: Journal of Neuroimmune Pharmacology: the Official Journal of the Society on NeuroImmune Pharmacology
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