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https://www.readbyqxmd.com/read/28077647/sensitive-next-generation-sequencing-method-reveals-deep-genetic-diversity-of-hiv-1-in-the-democratic-republic-of-the-congo
#1
M A Rodgers, E Wilkerson, A Vallari, C McArthur, L Sthreshley, C A Brennan, G Cloherty, T de Oliveira
: As the epidemiological epicentre of the human immunodeficiency virus (HIV) pandemic, the Democratic Republic of the Congo (DRC) is a reservoir of circulating HIV strains exhibiting high levels of diversity and recombination. In this study, we characterized HIV specimens collected in two rural areas of the DRC between 2001 and 2003 to identify rare strains of HIV. The env gp41 region was sequenced and characterized for 172 HIV-positive specimens. The env sequences were predominantly subtype A (43...
January 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28076882/characterization-of-salmonella-typhi-ompc-and-ompf-porins-engineered-with-hiv-gp41-epitope-on-the-surface-loops
#2
Madhuranayaki Thulasingam, Subha Damodharan, Gopal Madhana Vigneshwari, Eswari P J Pandaranayaka, Luke Elizabeth Hanna, Ramakrishnan Usha, Sankaran Krishnaswamy
Porins form trimers in the outer membrane and help transport nutrients and waste products across the bacterial cell membrane. Porin loops are suitable candidates as display systems due to their high immunogenicity and presentation at the bacterial cell surface. In this study, Salmonella typhi porins (OmpC and OmpF) engineered with the Kennedy peptide from gp41 of HIV were characterised. The chimeric OmpC carrying the Kennedy peptide in loop7 did not trimerise, whereas the chimeric OmpF with the epitope in loop5 formed trimers and also was recognised by the antibodies in the HIV patient serum...
January 11, 2017: Proteins
https://www.readbyqxmd.com/read/28076686/small-molecule-hiv-1-entry-inhibitors-targeting-gp120-and-gp41-a-patent-review-2010-2015
#3
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 11, 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
#4
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
#5
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/28051320/correlation-of-antibody-responses-to-a-peptide-antigen-gp120-c5-sup-501-512-sup-gp41-sup-732-744-sup-with-hiv-disease-progression
#6
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/28039275/qualitative-and-quantitative-hiv-antibodies-and-viral-reservoir-size-characterization-in-vertically-infected-children-with-virological-suppression
#7
Josephine Brice, Mariam Sylla, Sophie Sayon, Fatoumata Telly, Djeneba Bocar-Fofana, Robert Murphy, Sidonie Lambert-Niclot, Eve Todesco, Maxime Grude, Francis Barin, Souleymane Diallo, Deenan Pillay, Anne Derache, Vincent Calvez, Anne-Geneviève Marcelin, Almoustapha Issiaka Maiga
BACKGROUND: Absence of detectable viraemia after treatment cessation in some vertically HIV-infected (VHIV) children suggests that early initiation of HAART could lead to functional cure. OBJECTIVES: We described the factors associated with HIV antibody levels and the viral reservoir size in HAART-treated VHIV children. METHODS: Study included 97 VHIV children with virological suppression, in Bamako, Mali. The anti-gp41 antibody activities and HIV serostatus were assessed...
December 30, 2016: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28003492/residues-in-the-gp41-ectodomain-regulate-hiv-1-envelope-glycoprotein-conformational-transitions-induced-by-gp120-directed-inhibitors
#8
Beatriz Pacheco, Nirmin Alsahafi, Olfa Debbeche, Jérémie Prévost, Shilei Ding, Jean-Philippe Chapleau, Alon Herschhorn, Navid Madani, Amy Princiotto, Bruno Melillo, Christopher Gu, Xin Zeng, Youdong Mao, Amos B Smith, Joseph Sodroski, Andrés Finzi
: Interactions between the gp120 and gp41 subunits of the human immunodeficiency virus (HIV-1) envelope glycoprotein (Env) trimer maintain the metastable unliganded form of the viral spike. Binding of gp120 to the receptor, CD4, changes the Env conformation to promote gp120 interaction with the second receptor, CCR5 or CXCR4. CD4 binding also induces the transformation of Env into the pre-hairpin intermediate, in which the gp41 heptad repeat (HR1) coiled coil is assembled at the trimer axis...
December 21, 2016: Journal of Virology
https://www.readbyqxmd.com/read/28002738/construction-of-structural-mimetics-of-the-thyrotropin-receptor-intracellular-domain
#9
Olga Press, Tatiana Zvagelsky, Maria Vyazmensky, Gunnar Kleinau, Stanislav Engel
The signaling of a G protein-coupled receptor (GPCR) is dictated by the complementary responsiveness of interacting intracellular effectors such as G proteins. Many GPCRs are known to couple to more than one G protein subtype and induce a multitude of signaling pathways, although the in vivo relevance of particular pathways is mostly unrecognized. Dissecting GPCR signaling in terms of the pathways that are activated will boost our understanding of the molecular fundamentals of hormone action. The structural determinants governing the selectivity of GPCR/G protein coupling, however, remain obscure...
December 20, 2016: Biophysical Journal
https://www.readbyqxmd.com/read/27998850/-subtractive-selex-using-agar-beads-for-screening-dna-aptamers-with-specific-affinity-to-hiv-gp41-antigen
#10
Kun Li, Chen-Lin Xiu, Li-Ming Gao, Ming Shi, Yue Zhai
OBJECTIVE: To obtain DNA aptamers with a highly specific affinity to HIV gp41 antigen using SELEX screening for detection of HIV. METHODS: The specific DNA aptamers of HIV gp41 antigen were screened from the double-stranded DNA derived from the single-stranded DNA (ssDNA) library with agarose beads as the supportive medium and HIV gp41 antigen as the target molecule using SELEX technique and real-time quantitative PCR. RESULTS: The secondary ssDNA library obtained after 6 rounds of screening was amplified by PCR to obtain dsDNA...
December 20, 2016: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
https://www.readbyqxmd.com/read/27997339/toll-like-receptor-3-adjuvant-in-combination-with-virus-like-particles-elicit-a-humoral-response-against-hiv
#11
Ethan Poteet, Phoebe Lewis, Changyi Chen, Sam On Ho, Thai Do, SuMing Chiang, Celia Labranche, David Montefiori, Gary Fujii, Qizhi Yao
Human Immunodeficiency Virus (HIV) Virus-Like Particles (VLPs) composed of HIVIIIB Gag and HIVBaL gp120/gp41 envelope are a pseudovirion vaccine capable of presenting antigens in their native conformations. To enhance the immunogenicity of the HIV Env antigen, VLPs were coupled to VesiVax Conjugatable Adjuvant Lipid Vesicles (CALV) containing one of four toll-like-receptor (TLR) ligands, each activating a receptor with distinct cellular localization and downstream pathways. C57BL/6 mice were vaccinated by intranasal prime followed by two sub-cheek boosts and their sera immunoglobulin and neutralizing potency were measured over a duration of 3months after vaccination...
November 21, 2016: Vaccine
https://www.readbyqxmd.com/read/27992602/receptor-activation-of-hiv-1-env-leads-to-asymmetric-exposure-of-the-gp41-trimer
#12
Mukta D Khasnis, Konstantine Halkidis, Anshul Bhardwaj, Michael J Root
Structural rearrangements of HIV-1 glycoprotein Env promote viral entry through membrane fusion. Env is a symmetric homotrimer with each protomer composed of surface subunit gp120 and transmembrane subunit gp41. Cellular CD4- and chemokine receptor-binding to gp120 coordinate conformational changes in gp41, first to an extended prehairpin intermediate (PHI) and, ultimately, into a fusogenic trimer-of-hairpins (TOH). HIV-1 fusion inhibitors target gp41 in the PHI and block TOH formation. To characterize structural transformations into and through the PHI, we employed asymmetric Env trimers containing both high and low affinity binding sites for individual fusion inhibitors...
December 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27960171/are-basophils-and-mast-cells-masters-in-hiv-infection
#13
Gianni Marone, Gilda Varricchi, Stefania Loffredo, Maria Rosaria Galdiero, Felice Rivellese, Amato de Paulis
The World Health Organization AIDS epidemic update estimates that more than 37 million people are living with HIV infection. Despite the unprecedented success of antiretroviral treatments, significant challenges remain in the fight against HIV. In particular, how uninfected cells capture HIV and transmit virions to target cells remains an unanswered question. Tissue mast cells and peripheral blood basophils can be exposed to virions or HIV products during infection. Several HIV proteins (i.e., envelope glycoproteins gp120 and gp41, Tat, and Nef) can interact with distinct surface receptors expressed by human basophils and mast cells and modulate their functional responses at different levels...
2016: International Archives of Allergy and Immunology
https://www.readbyqxmd.com/read/27917706/the-changes-of-positive-selection-within-env-gene-of-hiv-1-b-crf07_bc-and-crf08_bc-from-china-over-time
#14
Tingting Li, Binlian Sun, Yanyan Jiang, Haiyan Zeng, Yanpeng Li, Yan Wang, Rongge Yang
: It is not clear about the possible evolutionary changes of the three predominant strains of HIV-1 in China over the course of the epidemic. Envelope (env) gene of HIV-1 is a good target for this evolutionary pressure for its enriched epitopes. METHODS: We collected 159 full or part of env sequences sampled between 1997 and 2010 from database of China, we calculated the genetic distance, detected the positively selected sites by PAML suite and then compared the number using Fisher's exact test between the early period 1997 to 2003and the late period2004 to 2010...
December 5, 2016: Current HIV Research
https://www.readbyqxmd.com/read/27908751/enhanced-potency-of-bivalent-small-molecule-gp41-inhibitors
#15
Vladimir Sofiyev, Hardeep Kaur, Beth A Snyder, Priscilla A Hogan, Roger G Ptak, Peter Hwang, Miriam Gochin
Low molecular weight peptidomimetic inhibitors with hydrophobic pocket binding properties and moderate fusion inhibitory activity against HIV-1 gp41-mediated cell fusion were elaborated by increasing the available surface area for interacting with the heptad repeat-1 (HR1) coiled coil on gp41. Two types of modifications were tested: 1) increasing the overall hydrophobicity of the molecules with an extension that could interact in the HR1 groove, and 2) forming symmetrical dimers with two peptidomimetic motifs that could potentially interact simultaneously in two hydrophobic pockets on the HR1 trimer...
January 1, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/27905530/structural-basis-for-broad-neutralization-of-hiv-1-through-the-molecular-recognition-of-10e8-helical-epitope-at-the-membrane-interface
#16
Edurne Rujas, Jose M M Caaveiro, Angélica Partida-Hanon, Naveed Gulzar, Koldo Morante, Beatriz Apellániz, Miguel García-Porras, Marta Bruix, Kouhei Tsumoto, Jamie K Scott, M Ángeles Jiménez, José L Nieva
The mechanism by which the HIV-1 MPER epitope is recognized by the potent neutralizing antibody 10E8 at membrane interfaces remains poorly understood. To solve this problem, we have optimized a 10E8 peptide epitope and analyzed the structure and binding activities of the antibody in membrane and membrane-like environments. The X-ray crystal structure of the Fab-peptide complex in detergents revealed for the first time that the epitope of 10E8 comprises a continuous helix spanning the gp41 MPER/transmembrane domain junction (MPER-N-TMD; Env residues 671-687)...
December 1, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27881646/activation-and-inactivation-of-primary-human-immunodeficiency-virus-envelope-glycoprotein-trimers-by-cd4-mimetic-compounds
#17
Navid Madani, Amy M Princiotto, Connie Zhao, Fatemeh Jahanbakhshsefidi, Max Mertens, Alon Herschhorn, Bruno Melillo, Amos B Smith, Joseph Sodroski
: Human immunodeficiency virus type 1 (HIV-1) entry into cells is mediated by the viral envelope glycoproteins (Env), a trimer of three gp120 exterior glycoproteins, and three gp41 transmembrane glycoproteins. The metastable Env is triggered to undergo entry-related conformational changes when gp120 binds sequentially to the receptors, CD4 and CCR5, on the target cell. Small-molecule CD4-mimetic compounds (CD4mc) bind gp120 and act as competitive inhibitors of gp120-CD4 engagement. Some CD4mc have been shown to trigger Env prematurely, initially activating Env function, followed by rapid and irreversible inactivation...
February 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/27855210/potent-and-broad-inhibition-of-hiv-1-by-a-peptide-from-the-gp41-heptad-repeat-2-domain-conjugated-to-the-cxcr4-amino-terminus
#18
George J Leslie, Jianbin Wang, Max W Richardson, Beth S Haggarty, Kevin L Hua, Jennifer Duong, Anthony J Secreto, Andrea P O Jordon, Josephine Romano, Kritika E Kumar, Joshua J DeClercq, Philip D Gregory, Carl H June, Michael J Root, James L Riley, Michael C Holmes, James A Hoxie
HIV-1 entry can be inhibited by soluble peptides from the gp41 heptad repeat-2 (HR2) domain that interfere with formation of the 6-helix bundle during fusion. Inhibition has also been seen when these peptides are conjugated to anchoring molecules and over-expressed on the cell surface. We hypothesized that potent anti-HIV activity could be achieved if a 34 amino acid peptide from HR2 (C34) were brought to the site of virus-cell interactions by conjugation to the amino termini of HIV-1 coreceptors CCR5 or CXCR4...
November 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27852851/identification-of-human-anti-hiv-gp160-monoclonal-antibodies-that-make-effective-immunotoxins
#19
Seth H Pincus, Kejing Song, Grace A Maresh, Dean H Hamer, Dimiter S Dimitrov, Weizao Chen, Mei-Yun Zhang, Victor F Ghetie, Po-Ying Chan-Hui, James E Robinson, Ellen S Vitetta
: The envelope (Env) glycoprotein of HIV is the only intact viral protein expressed on the surface of both virions and infected cells. Env is the target of neutralizing antibodies (Abs) and has been the subject of intense study in efforts to produce HIV vaccines. Therapeutic anti-Env Abs can also exert antiviral effects via Fc-mediated effector mechanisms or as cytotoxic immunoconjugates, such as immunotoxins (ITs). In the course of screening monoclonal antibodies (MAbs) for their ability to deliver cytotoxic agents to infected or Env-transfected cells, we noted disparities in their functional activities...
February 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/27849170/hiv-1-envelope-mimicry-of-host-enzyme-kynureninase-does-not-disrupt-tryptophan-metabolism
#20
Todd Bradley, Guang Yang, Olga Ilkayeva, T Matt Holl, Ruijun Zhang, Jinsong Zhang, Sampa Santra, Christopher B Fox, Steve G Reed, Robert Parks, Cindy M Bowman, Hilary Bouton-Verville, Laura L Sutherland, Richard M Scearce, Nathan Vandergrift, Thomas B Kepler, M Anthony Moody, Hua-Xin Liao, S Munir Alam, Roger McLendon, Jeffrey I Everitt, Christopher B Newgard, Laurent Verkoczy, Garnett Kelsoe, Barton F Haynes
The HIV-1 envelope protein (Env) has evolved to subvert the host immune system, hindering viral control by the host. The tryptophan metabolic enzyme kynureninase (KYNU) is mimicked by a portion of the HIV Env gp41 membrane proximal region (MPER) and is cross-reactive with the HIV broadly neutralizing Ab (bnAb) 2F5. Molecular mimicry of host proteins by pathogens can lead to autoimmune disease. In this article, we demonstrate that neither the 2F5 bnAb nor HIV MPER-KYNU cross-reactive Abs elicited by immunization with an MPER peptide-liposome vaccine in 2F5 bnAb VHDJH and VLJL knock-in mice and rhesus macaques modified KYNU activity or disrupted tissue tryptophan metabolism...
December 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
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