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https://www.readbyqxmd.com/read/29149197/sieve-analysis-of-breakthrough-hiv-1-sequences-in-hvtn-505-identifies-vaccine-pressure-targeting-the-cd4-binding-site-of-env-gp120
#1
Allan C deCamp, Morgane Rolland, Paul T Edlefsen, Eric Sanders-Buell, Breana Hall, Craig A Magaret, Andrew J Fiore-Gartland, Michal Juraska, Lindsay N Carpp, Shelly T Karuna, Meera Bose, Steven LePore, Shana Miller, Annemarie O'Sullivan, Kultida Poltavee, Hongjun Bai, Kalpana Dommaraju, Hong Zhao, Kim Wong, Lennie Chen, Hasan Ahmed, Derrick Goodman, Matthew Z Tay, Raphael Gottardo, Richard A Koup, Robert Bailer, John R Mascola, Barney S Graham, Mario Roederer, Robert J O'Connell, Nelson L Michael, Merlin L Robb, Elizabeth Adams, Patricia D'Souza, James Kublin, Lawrence Corey, Daniel E Geraghty, Nicole Frahm, Georgia D Tomaras, M Juliana McElrath, Lisa Frenkel, Sheila Styrchak, Sodsai Tovanabutra, Magdalena E Sobieszczyk, Scott M Hammer, Jerome H Kim, James I Mullins, Peter B Gilbert
Although the HVTN 505 DNA/recombinant adenovirus type 5 vector HIV-1 vaccine trial showed no overall efficacy, analysis of breakthrough HIV-1 sequences in participants can help determine whether vaccine-induced immune responses impacted viruses that caused infection. We analyzed 480 HIV-1 genomes sampled from 27 vaccine and 20 placebo recipients and found that intra-host HIV-1 diversity was significantly lower in vaccine recipients (P ≤ 0.04, Q-values ≤ 0.09) in Gag, Pol, Vif and envelope glycoprotein gp120 (Env-gp120)...
2017: PloS One
https://www.readbyqxmd.com/read/29143881/rmce-based-insect-cell-platform-to-produce-membrane-proteins-captured-on-hiv-1-gag-virus-like-particles
#2
João Vidigal, Bárbara Fernandes, Mafalda M Dias, Marco Patrone, António Roldão, Manuel J T Carrondo, Paula M Alves, Ana P Teixeira
Conformationally complex membrane proteins (MPs) are therapeutic targets in many diseases, but drug discovery has been slowed down by the lack of efficient production tools. Co-expression of MPs with matrix proteins from enveloped viruses is a promising approach to obtain correctly folded proteins at the surface of virus-like particles (VLPs), preserving their native lipidic environment. Here, we implemented a site-specific recombinase-mediated cassette exchange (RMCE) strategy to establish a reusable HIV-1 Gag-expressing insect cell line for fast production of target MPs on the surface of Gag-VLPs...
November 16, 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/29142315/hiv-1-counteracts-an-innate-restriction-by-amyloid-precursor-protein-resulting-in-neurodegeneration
#3
Qingqing Chai, Vladimir Jovasevic, Viacheslav Malikov, Yosef Sabo, Scott Morham, Derek Walsh, Mojgan H Naghavi
While beta-amyloid (Aβ), a classic hallmark of Alzheimer's disease (AD) and dementia, has long been known to be elevated in the human immunodeficiency virus type 1 (HIV-1)-infected brain, why and how Aβ is produced, along with its contribution to HIV-associated neurocognitive disorder (HAND) remains ill-defined. Here, we reveal that the membrane-associated amyloid precursor protein (APP) is highly expressed in macrophages and microglia, and acts as an innate restriction against HIV-1. APP binds the HIV-1 Gag polyprotein, retains it in lipid rafts and blocks HIV-1 virion production and spread...
November 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/29142136/size-composition-and-evolution-of-hiv-dna-populations-during-early-antiretroviral-therapy-and-intensification-with-maraviroc
#4
Antoine Chaillon, Sara Gianella, Steven M Lada, Josué Perez-Santiago, Parris Jordan, Caroline Ignacio, Maile Karris, Douglas Richman, Sanjay R Mehta, Susan J Little, Joel O Wertheim, Davey M Smith
Residual viremia is common during antiretroviral therapy (ART), and could be caused by ongoing low-level virus replication or by release of viral particles from infected cells. ART Intensification should impact ongoing viral propagation but not virion release. Eighteen acutely infected men were enrolled in a randomized controlled trial, and followed for a median of 107 weeks. Participants started ART with (n=9) or without (n=9) intensification with maraviroc (MVC) within 90 days of infection. Levels of HIV DNA and cell-free RNA were quantified by droplet digital PCR...
November 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29135573/evidence-of-inflammasome-activation-and-formation-of-monocyte-derived-apoptosis-associated-speck-like-protein-containing-a-caspase-recruitment-domain-specks-in-hiv-1-positive-patients
#5
Fareed Ahmad, Neha Mishra, Gerrit Ahrenstorf, Bernardo S Franklin, Eicke Latz, Reinhold E Schmidt, Lukas Bossaller
OBJECTIVE: The formation of large intracellular protein aggregates of the inflammasome adaptor apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC) (PYCARD) is a hallmark of inflammasome activation. ASC speck-forming cells release the highly proinflammatory cytokine IL-1β in addition to ASC specks into the extracellular space during pyroptotic cell death. There ASC specks can propagate inflammation to other nonactivated cells or tissues. HIV-1 retroviral infection triggers inflammasome activation of abortively infected CD4 T cells in secondary lymphatic tissues...
November 10, 2017: AIDS
https://www.readbyqxmd.com/read/29127210/hiv-1-nc-induced-stress-granule-assembly-and-translation-arrest-are-inhibited-by-the-dsrna-binding-protein-staufen1
#6
Shringar Rao, Alessandro Cinti, Abdelkrim Temzi, Raquel Amorim, Ji Chang You, Andrew J Mouland
The nucleocapsid (NC) is an N-terminal protein derived from the HIV-1 Gag precursor polyprotein, pr55Gag. NC possesses key functions at several pivotal stages of viral replication. For example, an interaction between NC and the host, double-stranded RNA-binding protein Staufen1 was shown to regulate several steps in the viral replication cycle, such as Gag multimerisation and genomic RNA encapsidation. In this work, we observed that the overexpression of NC leads to the induction of stress granule (SG) assembly...
November 10, 2017: RNA
https://www.readbyqxmd.com/read/29124093/analysis-of-the-conformations-of-the-hiv-1-protease-from-a-large-crystallographic-data-set
#7
Luigi Leonardo Palese
The HIV-1 protease performs essential roles in viral maturation by processing specific cleavage sites in the Gag and Gag-Pol precursor polyproteins to release their mature forms. Here the analysis of a large HIV-1 protease data set (containing 552 dimer structures) are reported. These data are related to article entitled "Conformations of the HIV-1 protease: a crystal structure data set analysis" (Palese, 2017) [1].
December 2017: Data in Brief
https://www.readbyqxmd.com/read/29123989/fret-analysis-of-hiv-1-gag-and-gagpol-interactions
#8
Shimon Takagi, Fumitaka Momose, Yuko Morikawa
The Gag protein of HIV multimerizes to form viral particles. The GagPol protein encoding virus-specific enzymes, such as protease, reverse transcriptase, and integrase, is incorporated into HIV particles via interactions with Gag. The catalytically active forms of these enzymes are dimeric or tetrameric. We employed Förster resonance energy transfer (FRET) assays to evaluate Gag-Gag, Gag-GagPol, and GagPol-GagPol interactions and investigated Gag and Pol interdomains tolerant to fluorescent protein insertion for FRET assays...
November 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/29123089/tsg101-chaperone-function-revealed-by-hiv-1-assembly-inhibitors
#9
Madeleine Strickland, Lorna S Ehrlich, Susan Watanabe, Mahfuz Khan, Marie-Paule Strub, Chi-Hao Luan, Michael D Powell, Jonathan Leis, Nico Tjandra, Carol A Carter
HIV-1 replication requires Tsg101, a component of cellular endosomal sorting complex required for transport (ESCRT) machinery. Tsg101 possesses an ubiquitin (Ub) E2 variant (UEV) domain with a pocket that can bind PT/SAP motifs and another pocket that can bind Ub. The PTAP motif in the viral structural precursor polyprotein, Gag, allows the recruitment of Tsg101 and other ESCRTs to virus assembly sites where they mediate budding. It is not known how or even whether the UEV Ub binding function contributes to virus production...
November 9, 2017: Nature Communications
https://www.readbyqxmd.com/read/29121951/increasing-the-cpg-dinucleotide-abundance-in-the-hiv-1-genomic-rna-inhibits-viral-replication
#10
Irati Antzin-Anduetza, Charlotte Mahiet, Luke A Granger, Charlotte Odendall, Chad M Swanson
BACKGROUND: The human immunodeficiency virus type 1 (HIV-1) structural protein Gag is necessary and sufficient to form viral particles. In addition to encoding the amino acid sequence for Gag, the underlying RNA sequence could encode cis-acting elements or nucleotide biases that are necessary for viral replication. Furthermore, RNA sequences that inhibit viral replication could be suppressed in gag. However, the functional relevance of RNA elements and nucleotide biases that promote or repress HIV-1 replication remain poorly understood...
November 9, 2017: Retrovirology
https://www.readbyqxmd.com/read/29121950/the-hiv-1-integrase-ledgf-allosteric-inhibitor-mut-a-resistance-profile-impairment-of-virus-maturation-and-infectivity-but-without-influence-on-rna-packaging-or-virus-immunoreactivity
#11
Céline Amadori, Yme Ubeles van der Velden, Damien Bonnard, Igor Orlov, Nikki van Bel, Erwann Le Rouzic, Laia Miralles, Julie Brias, Francis Chevreuil, Daniele Spehner, Sophie Chasset, Benoit Ledoussal, Luzia Mayr, François Moreau, Felipe García, José Gatell, Alessia Zamborlini, Stéphane Emiliani, Marc Ruff, Bruno P Klaholz, Christiane Moog, Ben Berkhout, Montserrat Plana, Richard Benarous
BACKGROUND: HIV-1 Integrase (IN) interacts with the cellular co-factor LEDGF/p75 and tethers the HIV preintegration complex to the host genome enabling integration. Recently a new class of IN inhibitors was described, the IN-LEDGF allosteric inhibitors (INLAIs). Designed to interfere with the IN-LEDGF interaction during integration, the major impact of these inhibitors was surprisingly found on virus maturation, causing a reverse transcription defect in target cells. RESULTS: Here we describe the MUT-A compound as a genuine INLAI with an original chemical structure based on a new type of scaffold, a thiophene ring...
November 9, 2017: Retrovirology
https://www.readbyqxmd.com/read/29117524/cholesterol-promotes-protein-binding-by-affecting-membrane-electrostatics-and-solvation-properties
#12
Milka Doktorova, Frederick A Heberle, Richard L Kingston, George Khelashvili, Michel A Cuendet, Yi Wen, John Katsaras, Gerald W Feigenson, Volker M Vogt, Robert A Dick
Binding of the retroviral structural protein Gag to the cellular plasma membrane is mediated by the protein's matrix (MA) domain. Prominent among MA-PM interactions is electrostatic attraction between the positively charged MA domain and the negatively charged plasma membrane inner leaflet. Previously, we reported that membrane association of HIV-1 Gag, as well as purified Rous sarcoma virus (RSV) MA and Gag, depends strongly on the presence of acidic lipids and is enhanced by cholesterol (Chol). The mechanism underlying this enhancement was unclear...
November 7, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/29114997/in-vitro-modeling-of-hiv-proviral-activity-in-microglia
#13
Lee A Campbell, Christopher T Richie, Yajun Zhang, Emily J Heathward, Lamarque M Coke, Emily Y Park, Brandon K Harvey
Microglia, the resident macrophages of the brain, play a key role in the pathogenesis of HIV-associated neurocognitive disorders (HAND) due to their productive infection by HIV. This results in the release of neurotoxic viral proteins and pro-inflammatory compounds which negatively affect the functionality of surrounding neurons. Because models of HIV infection within the brain are limited, we aimed to create a novel microglia cell line with an integrated HIV provirus capable of recreating several hallmarks of HIV infection...
November 8, 2017: FEBS Journal
https://www.readbyqxmd.com/read/29114055/immature-hiv-1-lattice-assembly-dynamics-are-regulated-by-scaffolding-from-nucleic-acid-and-the-plasma-membrane
#14
Alexander J Pak, John M A Grime, Prabuddha Sengupta, Antony K Chen, Aleksander E P Durumeric, Anand Srivastava, Mark Yeager, John A G Briggs, Jennifer Lippincott-Schwartz, Gregory A Voth
The packaging and budding of Gag polyprotein and viral RNA is a critical step in the HIV-1 life cycle. High-resolution structures of the Gag polyprotein have revealed that the capsid (CA) and spacer peptide 1 (SP1) domains contain important interfaces for Gag self-assembly. However, the molecular details of the multimerization process, especially in the presence of RNA and the cell membrane, have remained unclear. In this work, we investigate the mechanisms that work in concert between the polyproteins, RNA, and membrane to promote immature lattice growth...
November 7, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29098809/gp41-and-gag-amino-acids-linked-to-hiv-1-protease-inhibitor-based-second-line-failure-in-hiv-1-subtype-a-from-western-kenya
#15
Mia Coetzer, Lauren Ledingham, Lameck Diero, Emmanuel Kemboi, Millicent Orido, Rami Kantor
INTRODUCTION: Failure of protease-inhibitor (PI)-based second-line antiretroviral therapy (ART) with medication adherence but no protease drug resistance mutations (DRMs) is not well understood. This study investigated the involvement of gp41 and gag as alternative mechanisms, not captured by conventional resistance testing and particularly relevant in resource-limited settings where third-line ART is limited. METHODS: We evaluated gp41 and gag for unique amino acids in seven subtype A infected Kenyans failing second-line therapy with no PI resistance yet detectable lopinavir (query dataset), compared to seven similar-setting patients with PI resistance or undetectable lopinavir and 69 publically available subtype A Kenyan whole-genomes sequences...
November 2017: Journal of the International AIDS Society
https://www.readbyqxmd.com/read/29093100/weaker-hla-footprints-on-hiv-in-the-unique-and-highly-genetically-admixed-host-population-of-mexico
#16
Maribel Soto-Nava, Santiago Avila-Ríos, Humberto Valenzuela-Ponce, Claudia García-Morales, Jonathan M Carlson, Daniela Tapia-Trejo, Daniela Garrido-Rodriguez, Selma N Alva-Hernández, Thalía A García-Tellez, Akio Murakami-Ogasawara, Simon A Mallal, Mina John, Mark A Brockman, Chanson J Brumme, Zabrina L Brumme, Gustavo Reyes-Teran
HIV circumvents HLA class I-restricted CD8+ T cell responses through selection of escape mutations that leave characteristic mutational "footprints" - also known as HLA-associated polymorphisms (HAPs) - on HIV sequences at the population level. While many HLA footprints are universal across HIV subtypes and human populations, others can be region-specific as a result of the unique immunogenetic background of each host population. Using a published probabilistic phylogenetically-informed model, we compared HAPs in HIV Gag and Pol (PR-RT) in 1,612 subtype B-infected, antiretroviral treatment-naïve individuals from Mexico and 1,641 from Canada/USA...
November 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29093095/combination-adenovirus-and-protein-vaccines-prevent-infection-or-reduce-viral-burden-after-heterologous-clade-c-shiv-mucosal-challenge
#17
Delphine C Malherbe, Jason Mendy, Lo Vang, Philip T Barnette, Jason Reed, Samir K Lakhashe, Joshua Owuor, Johannes S Gach, Alfred W Legasse, Michael K Axthelm, Celia C LaBranche, David Montefiori, Donald N Forthal, Byung Park, James M Wilson, James H McLinden, Jinhua Xiang, Jack T Stapleton, Jonah B Sacha, Barton F Haynes, Hua-Xin Liao, Ruth M Ruprecht, Jonathan Smith, Marc Gurwith, Nancy L Haigwood, Jeff Alexander
HIV vaccine development is focused on designing immunogens and delivery methods that elicit protective immunity. We evaluated a combination of Ad vectors expressing HIV 1086.C (Clade C) Envelope glycoprotein, SIV Gag p55, and human pegivirus GBV-C E2 glycoprotein. We compared replicating simian (SAd7) with non-replicating human (Ad4) adenovirus-vectored vaccines paired with recombinant proteins in a novel prime-boost regimen in rhesus macaques, with the goal of eliciting protective immunity against SHIV challenge...
November 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29091580/epidemiology-reveals-zhaotong-city-as-the-hub-of-human-immunodeficiency-virus-type-1-transmission-from-the-yunnan-province-to-other-regions-in-china
#18
Li Ren, Bingbui Wang, Kunmei Gong, Pan Liu, Shiyi Zhou, Li Zhang, Xueshan Xia, Kunhua Wang
The Yunnan province in China has a high incidence of human immunodeficiency virus-1 (HIV-1) infection. Zhaotong City is located in the Yunnan province, a neglected 'important region'. In this study, we evaluated the unique molecular epidemiological characteristics of HIV-1 infection in Zhaotong City. We collected 305 serum samples from HIV-infected patients in Zhaotong City between May 2015 and April 2016. A total of 122 samples were selected for HIV-1 gag-pol gene amplification, of which 88 were successfully amplified and sequenced for phylogenetic and phylogeographic analysis...
November 1, 2017: Journal of General Virology
https://www.readbyqxmd.com/read/29091184/prevalence-of-gag-mutations-associated-with-in-vitro-resistance-to-capsid-inhibitor-gs-ca1-in-hiv-1-antiretroviral-naive-patients
#19
Marine Perrier, Mélanie Bertine, Quentin Le Hingrat, Véronique Joly, Benoit Visseaux, Gilles Collin, Roland Landman, Yazdan Yazdanpanah, Diane Descamps, Charlotte Charpentier
No abstract text is available yet for this article.
October 1, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/29080666/topically-applied-virus-like-particles-containing-hiv-1-pr55-gag-protein-reach-skin-antigen-presenting-cells-after-mild-skin-barrier-disruption
#20
Fiorenza Rancan, Zahra Afraz, Sabrina Hadam, Lina Weiß, Hélène Perrin, Alexander Kliche, Petra Schrade, Sebastian Bachmann, Monika Schäfer-Korting, Ulrike Blume-Peytavi, Ralf Wagner, Béhazine Combadière, Annika Vogt
Loading of antigen on particles as well as the choice of skin as target organ for vaccination were independently described as effective dose-sparing strategies for vaccination. Combining these two strategies, sufficient antigen recognition may be achievable via the transcutaneous route even with minimal-invasive tools. Here, we investigated the skin penetration and cellular uptake of topically administered virus-like particles (VLPs), composed of the HIV-1 precursor protein Pr55(gag), as well as the migratory activity of skin antigen-presenting cells (APCs)...
November 2, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
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