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https://www.readbyqxmd.com/read/29346774/mannose-receptor-1-restricts-hiv-particle-release-from-infected-macrophages
#1
Sayaka Sukegawa, Eri Miyagi, Fadila Bouamr, Helena Farkašová, Klaus Strebel
Human mannose receptor 1 (hMRC1) is expressed on the surface of most tissue macrophages, dendritic cells, and select lymphatic or liver endothelial cells. HMRC1 contributes to the binding of HIV-1 to monocyte-derived macrophages (MDMs) and is involved in the endocytic uptake of HIV-1 into these cells. Here, we identify hMRC1 as an antiviral factor that inhibits virus release through a bone marrow stromal antigen 2 (BST-2)-like mechanism. Virions produced in the presence of hMRC1 accumulated in clusters at the cell surface but were fully infectious...
January 16, 2018: Cell Reports
https://www.readbyqxmd.com/read/29343613/restricted-hiv-1-env-glycan-engagement-by-lectin-reengineered-davei-protein-chimera-is-sufficient-for-lytic-inactivation-of-the-virus
#2
Bibek Parajuli, Kriti Acharya, Harry C Bach, Bijay Parajuli, Shiyu Zhang, Amos B Smith, Cameron F Abrams, Irwin Chaiken
We previously reported first generation recombinant DAVEI construct, a dual action virus entry inhibitor composed of cyanovirin-N (CVN) fused to a membrane proximal external region (MPER) or its derivative peptide Trp3. DAVEI exhibits potent and irreversible inactivation of HIV-1 viruses by dual engagement of gp120 and gp41. However, the promiscuity of CVN to associate with multiple glycosylation sites in gp120 and its multivalency limit current understanding of the molecular arrangement of the DAVEI molecules on trimeric spike...
January 17, 2018: Biochemical Journal
https://www.readbyqxmd.com/read/29339801/cardiac-glycoside-aglycones-inhibit-hiv-1-gene-expression-by-a-mechanism-requiring-mek1-2-erk1-2-signaling
#3
Raymond W Wong, Clifford A Lingwood, Mario A Ostrowski, Tyler Cabral, Alan Cochrane
The capacity of HIV-1 to develop resistance to current drugs calls for innovative strategies to control this infection. We aimed at developing novel inhibitors of HIV-1 replication by targeting viral RNA processing-a stage dependent on conserved host processes. We previously reported that digoxin is a potent inhibitor of this stage. Herein, we identify 12 other cardiac glycoside/aglycones or cardiotonic steroids (CSs) that impede HIV growth in HIV-infected T cells from clinical patients at IC50s (1.1-1.3 nM) that are 2-26 times below concentrations used in patients with heart conditions...
January 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29325070/vaccine-induced-antibody-responses-modify-the-association-between-t-cell-immune-responses-and-hiv-1-infection-risk-in-hvtn-505
#4
Youyi Fong, Xiaoying Shen, Vicki C Ashley, Aaron Deal, Kelly E Seaton, Chenchen Yu, Shannon P Grant, Guido Ferrari, Allan C deCamp, Robert T Bailer, Richard A Koup, David Montefiori, Barton F Haynes, Marcella Sarzotti-Kelsoe, Barney S Graham, Lindsay N Carpp, Scott M Hammer, Magda Sobieszczyk, Shelly Karuna, Edith Swann, Edwin DeJesus, Mark Mulligan, Ian Frank, Susan Buchbinder, Richard M Novak, M Juliana McElrath, Spyros Kalams, Michael Keefer, Nicole A Frahm, Holly E Janes, Peter B Gilbert, Georgia D Tomaras
Background: HVTN 505 was an HIV-1 preventive vaccine efficacy trial of a DNA/recombinant adenovirus serotype 5 (rAd5) vaccine regimen. We assessed antibody responses measured one month post-final vaccination (Month 7) as correlates of HIV-1 acquisition risk. Methods: Binding antibody responses were quantified in serum samples from 25 primary endpoint vaccine cases (diagnosed with HIV-1 infection between Month 7 and 24) and 125 randomly sampled frequency-matched vaccine controls (HIV-1 negative at Month 24)...
January 8, 2018: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29310678/computational-analysis-of-envelope-glycoproteins-from-diverse-geographical-isolates-of-bovine-leukemia-virus-identifies-highly-conserved-peptide-motifs
#5
Aneta Pluta, Lorraine M Albritton, Marzena Rola-Łuszczak, Jacek Kuźmak
BACKGROUND: Bovine leukemia virus (BLV) is a deltaretrovirus infecting bovine B cells and causing enzootic bovine leucosis. The SU or surface subunit, gp51, of its envelope glycoprotein is involved in receptor recognition and virion attachment. It contains the major neutralizing and CD4+ and CD8+ T cell epitopes found in naturally infected animals. In this study, we aimed to determine global variation and conservation within gp51 in the context of developing an effective global BLV vaccine...
January 8, 2018: Retrovirology
https://www.readbyqxmd.com/read/29298890/full-length-glycosylated-gag-of-murine-leukemia-virus-can-associate-with-the-viral-envelope-as-a-type-i-integral-membrane-protein
#6
Tyler Milston Renner, Kasandra Bélanger, Cindy Lam, Maria Rosales Gerpe, Joanne Eileen McBane, Marc-André Langlois
The glycosylated Gag protein (gPr80) of murine leukemia viruses (MLVs) has been shown to exhibit multiple roles in facilitating retrovirus release, infection and resistance to host-encoded retroviral restriction factors such as APOBEC3, SERINC3 and SERINC5. One way gPr80 helps MLVs escape host innate immune restriction is by increasing capsid stability, a feature that protects viral replication intermediates from being detected by cytosolic DNA sensors. gPr80 also increases the resistance of MLVs against deamination and restriction by mouse APOBEC3 (mA3)...
January 3, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29296883/innate-transcriptional-effects-by-adjuvants-on-the-magnitude-quality-and-durability-of-hiv-envelope-responses-in-nhps
#7
Joseph R Francica, Daniel E Zak, Caitlyn Linde, Emilio Siena, Carrie Johnson, Michal Juraska, Nicole L Yates, Bronwyn Gunn, Ennio De Gregorio, Barbara J Flynn, Nicholas M Valiante, Padma Malyala, Susan W Barnett, Pampi Sarkar, Manmohan Singh, Siddhartha Jain, Margaret Ackerman, Munir Alam, Guido Ferrari, Georgia D Tomaras, Derek T O'Hagan, Alan Aderem, Galit Alter, Robert A Seder
Adjuvants have a critical role for improving vaccine efficacy against many pathogens, including HIV. Here, using transcriptional RNA profiling and systems serology, we assessed how distinct innate pathways altered HIV-specific antibody responses in nonhuman primates (NHPs) using 8 clinically based adjuvants. NHPs were immunized with a glycoprotein 140 HIV envelope protein (Env) and insoluble aluminum salts (alum), MF59, or adjuvant nanoemulsion (ANE) coformulated with or without Toll-like receptor 4 (TLR4) and 7 agonists...
November 28, 2017: Blood Advances
https://www.readbyqxmd.com/read/29237847/a-trimeric-hiv-1-envelope-gp120-immunogen-induces-potent-and-broad-anti-v1v2-loop-antibodies-against-hiv-1-in-rabbits-and-rhesus-macaques
#8
Andrew T Jones, Venkateswarlu Chamcha, Sannula Kesavardhana, Xiaoying Shen, David Beaumont, Raksha Das, Linda S Wyatt, Celia C LaBranche, Sherry Stanfield-Oakley, Guido Ferrari, David C Montefiori, Bernard Moss, Georgia D Tomaras, Raghavan Varadarajan, Rama Rao Amara
Trimeric HIV-1 envelope (Env) immunogens are attractive due to their ability to display quaternary epitopes targeted by broadly neutralizing antibodies while obscuring unfavorable epitopes. Results from the RV144 trial highlighted the importance of vaccine induced HIV-1 Env V1V2 directed antibodies, with key regions of the V2 loop as targets for vaccine-mediated protection. We recently reported that a trimeric JRFL-gp120 immunogen, generated by inserting a N-terminal trimerization domain in the V1 loop region of a cyclically permuted gp120 (cycP-gp120), induces neutralizing activity against multiple tier-2 HIV-1 isolates in guinea pigs in a DNA prime/protein boost approach...
December 13, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29217761/aptamer-conjugated-extracellular-nanovesicles-for-targeted-drug-delivery
#9
Yuan Wan, Lixue Wang, Chuandong Zhu, Qin Zheng, Guoxiang Wang, Jinlong Tong, Yuan Fang, Yiqiu Xia, Gong Cheng, Xia He, Si-Yang Zheng
Extracellular nanovesicles (ENV) released by many cells contain lipids, proteins and nucleic acids that contribute to intercellular communication. ENV have emerged as biomarkers and therapeutic targets but they have also been explored as drug delivery vehicles. However, for the latter application clinical translation has been limited by low yield and inadequate targeting effects. ENV vectors with desired targeting properties can be produced from parental cells engineered to express membrane-bound targeting ligands, or they can be generated by fusion with targeting liposomes, however, neither approach has met clinical requirements...
December 7, 2017: Cancer Research
https://www.readbyqxmd.com/read/29212940/hiv-1-envelope-glycoprotein-trafficking-through-the-endosomal-recycling-compartment-is-required-for-particle-incorporation
#10
Junghwa Kirschman, Mingli Qi, Lingmei Ding, Jason Hammonds, Krista Dienger-Stambaugh, Jaang-Jiun Wang, Lynne A Lapierre, James R Goldenring, Paul Spearman
The HIV-1 envelope glycoprotein (Env) encodes specific trafficking signals within its long cytoplasmic tail (CT) that regulate incorporation into HIV-1 particles. Rab11-Family Interacting Protein 1C (FIP1C) and Rab14 are host trafficking factors required for Env particle incorporation, suggesting that Env undergoes sorting from the endosomal recycling compartment (ERC) to the site of particle assembly on the plasma membrane. We disrupted outward sorting from the ERC by expressing a C-terminal fragment of FIP1C (FIP1C560-649) and examined the consequences on Env trafficking and incorporation into particles...
December 6, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29212930/control-of-htlv-1-infection-by-eliminating-envelope-protein-positive-cells-with-recombinant-vesicular-stomatitis-viruses-encoding-htlv-1-primary-receptor
#11
Kenta Tezuka, Kazu Okuma, Madoka Kuramitsu, Sahoko Matsuoka, Reiko Tanaka, Yuetsu Tanaka, Isao Hamaguchi
Human T-cell leukemia virus type 1 (HTLV-1) infection causes adult T-cell leukemia (ATL), which is frequently resistant to current available therapies and has a very poor prognosis. To prevent the development of ATL among carriers it is important to control HTLV-1-infected cells in infected individuals. Therefore, the establishment of novel therapies with drugs specifically targeting infected cells is urgently required. This study aimed to develop a potential therapy by generating recombinant vesicular stomatitis viruses (rVSVs) that lack an envelope glycoprotein G and instead encode HTLV-1 receptor(s) with human glucose transporter 1 (GLUT1), neuropilin 1 (NRP1), or heparan sulfate proteoglycans (HSPGs) including syndecan 1 (SDC1), designated as VSVΔG-GL, VSVΔG-NP, or VSVΔG-SD, respectively...
December 6, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29193965/stability-and-water-accessibility-of-the-trimeric-membrane-anchors-of-the-hiv-1-envelope-spikes
#12
Alessandro Piai, Jyoti Dev, Qingshan Fu, James J Chou
HIV-1 envelope spike (Env) is a type I membrane protein that mediates viral entry. Recent studies showed that its transmembrane domain (TMD) forms a trimer in lipid bilayer whose structure has several peculiar features that remain difficult to explain. One is the presence of an arginine R696 in the middle of the TM helix. Additionally, the N- and C-terminal halves of the TM helix form trimeric cores of opposite nature (hydrophobic and hydrophilic, respectively). Here we determined the membrane partition and solvent accessibility of the TMD in bicelles that mimic a lipid bilayer...
December 1, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/29187598/epitope-focused-immunogens-against-the-cd4-binding-site-of-hiv-1-envelope-protein-induce-neutralizing-antibodies-against-auto-and-heterologous-viruses
#13
Hua Wang, Xiangjun Chen, Dianhong Wang, Chen Yao, Qian Wang, Jiayu Xie, Xuanling Shi, Ye Xiang, Wanli Liu, Linqi Zhang
Recent discoveries of broadly neutralizing antibodies (bnAbs) in HIV-1-infected individuals have led to the identification of several major ″vulnerable sites″ on the HIV-1 envelope (Env) glycoprotein. These sites have provided precise targets for HIV-1 vaccine development, but identifying and utilizing many of these targets remains technically challenging. Using a yeast surface display-based approach, we sought to identify epitope-focused antigenic domains (EADs) containing one of the ″vulnerable sites″, the CD4-binding site (CD4bs), through screening and selection of a combinatorial antigen library of the HIV-1 Env glycoprotein with the CD4bs bnAb VRC01...
November 29, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29187544/genetically-intact-but-functionally-impaired-hiv-1-env-glycoproteins-in-the-t-cell-reservoir
#14
Anne de Verneuil, Julie Migraine, Fabrizio Mammano, Jean-Michel Molina, Sébastien Gallien, Hugo Mouquet, Allan J Hance, François Clavel, Jacques Dutrieux
HIV-infected subjects under ART harbor a persistent viral reservoir in resting CD4+ T-cells, which accounts for the resurgence of HIV replication after ART interruption. A large majority of HIV reservoir genomes are genetically defective, but even among intact proviruses, few seem able to generate infectious virus. To understand this phenomenon, we have examined the function and expression of HIV envelope glycoproteins reactivated from the reservoir of 4 HIV-infected subjects under suppressive ART. We studied full-length genetically intact env sequences from both replicative viruses and cell-associated mRNAs...
November 29, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29175625/increased-surface-expression-of-hiv-1-envelope-is-associated-with-improved-antibody-response-in-vaccinia-prime-protein-boost-immunization
#15
Michael J Hogan, Angela Conde-Motter, Andrea P O Jordan, Lifei Yang, Brad Cleveland, Wenjin Guo, Josephine Romano, Houping Ni, Norbert Pardi, Celia C LaBranche, David C Montefiori, Shiu-Lok Hu, James A Hoxie, Drew Weissman
HIV-1 envelope (Env)-based vaccines have so far largely failed to induce antibodies that prevent HIV-1 infection. One factor proposed to limit the immunogenicity of cell-associated Env is its low level of expression on the cell surface, restricting accessibility to antibodies. Using a vaccinia prime/protein boost protocol in mice, we explored the immunologic effects of mutations in the Env cytoplasmic tail (CT) that increased surface expression, including partial truncation and ablation of a tyrosine-dependent endocytosis motif...
November 22, 2017: Virology
https://www.readbyqxmd.com/read/29173180/the-neutralizing-antibody-response-to-the-hiv-1-env-protein
#16
Penny L Moore
BACKGROUND: A vaccine able to elicit broadly neutralizing antibodies capable of blocking infection by global viruses has not been achieved, and remains a key public health challenge. OBJECTIVE: During infection, a robust strain-specific neutralizing response develops in most people, but only a subset of infected people develop broadly neutralizing antibodies. Understanding how and why these broadly neutralizing antibodies develop has been a focus of the HIV-1 vaccine field for many years, and has generated extraordinary insights into the neutralizing response to HIV-1 infection...
November 24, 2017: Current HIV Research
https://www.readbyqxmd.com/read/29162694/an-endogenous-retroviral-envelope-syncytin-and-its-cognate-receptor-identified-in-the-viviparous-placental-mabuya-lizard
#17
Guillaume Cornelis, Mathis Funk, Cécile Vernochet, Francisca Leal, Oscar Alejandro Tarazona, Guillaume Meurice, Odile Heidmann, Anne Dupressoir, Aurélien Miralles, Martha Patricia Ramirez-Pinilla, Thierry Heidmann
Syncytins are envelope genes from endogenous retroviruses that have been captured during evolution for a function in placentation. They have been found in all placental mammals in which they have been searched, including marsupials. Placental structures are not restricted to mammals but also emerged in some other vertebrates, most frequently in lizards, such as the viviparous Mabuya Scincidae. Here, we performed high-throughput RNA sequencing of a Mabuya placenta transcriptome and screened for the presence of retroviral env genes with a full-length ORF...
November 21, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29150937/cgmp-production-and-analysis-of-bg505-sosip-664-an-extensively-glycosylated-trimeric-hiv-1-envelope-glycoprotein-vaccine-candidate
#18
Antu K Dey, Albert Cupo, Gabriel Ozorowski, Vaneet K Sharma, Anna-Janina Behrens, Eden P Go, Thomas J Ketas, Anila Yasmeen, Per J Klasse, Eddy Sayeed, Heather Desaire, Max Crispin, Ian A Wilson, Rogier W Sanders, Thomas Hassell, Andrew Ward, John P Moore
We describe the properties of BG505 SOSIP.664 HIV-1 envelope glycoprotein trimers produced under current Good Manufacturing Practice (cGMP) conditions. These proteins are the first of a new generation of native-like trimers that are the basis for many structure-guided immunogen development programs aimed at devising how to induce broadly neutralizing antibodies (bNAbs) to HIV-1 by vaccination. The successful translation of this prototype demonstrates the feasibility of producing similar immunogens on an appropriate scale and of an acceptable quality for Phase I experimental medicine clinical trials...
November 18, 2017: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/29150603/bacterially-derived-synthetic-mimetics-of-mammalian-oligomannose-prime-antibody-responses-that-neutralize-hiv-infectivity
#19
Ralph Pantophlet, Nino Trattnig, Sasha Murrell, Naiomi Lu, Dennis Chau, Caitlin Rempel, Ian A Wilson, Paul Kosma
Oligomannose-type glycans are among the major targets on the gp120 component of the HIV envelope protein (Env) for broadly neutralizing antibodies (bnAbs). However, attempts to elicit oligomannose-specific nAbs by immunizing with natural or synthetic oligomannose have so far not been successful, possibly due to B cell tolerance checkpoints. Here we design and synthesize oligomannose mimetics, based on the unique chemical structure of a recently identified bacterial lipooligosaccharide, to appear foreign to the immune system...
November 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/29142124/truncating-the-gp41-cytoplasmic-tail-of-siv-decreases-sensitivity-to-neutralizing-antibodies-without-increasing-envelope-content-of-virions
#20
Ellen White, Fan Wu, Elena Chertova, Julian Bess, James D Roser, Jeffrey D Lifson, Vanessa M Hirsch
An incomplete understanding of native HIV and SIV envelope glycoprotein (Env) impedes the development of structural models of Env and vaccine design. This shortcoming is due in part to the low number of Env trimers on virus particles. For SIV, this low expression can be counteracted by truncating the cytoplasmic tail (CT) of Env. CT truncation has been shown to increase Env incorporation into the virion and is commonly used in vaccine and imaging studies, but its effects on viral antigenicity have not been fully elucidated...
November 15, 2017: Journal of Virology
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