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https://www.readbyqxmd.com/read/28324619/identification-of-a-herv-k-env-surface-peptide-highly-recognized-in-ra-patients-a-cross-sectional-case-control-study
#1
G Mameli, G L Erre, E Caggiu, S Mura, D Cossu, Marco Bo, M L Cadoni, A Piras, N Mundula, E Colombo, G Buscetta, G Passiu, L A Sechi
Endogenous Retroviruses (HERV) are believed to be pathogenic in several autoimmune diseases. Among them, HERV-K viruses have been recently reported to be involved in the pathogenesis of rheumatoid arthritis (RA). In this study we have explored the role of humoral immune response against HERV-K as a potential pathogenetic mechanism in RA. Four different peptides from the extracellular portion of the env protein of HERV-K (env-su 19-37 , env-su 109-26 , env-su 164-186 , env-su 209-226 ) were selected by bioinformatic analysis on the basis of their putative immunogenicity...
March 21, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28314374/hiv-1-consensus-envelope-induced-broadly-binding-antibodies
#2
R Ryan Meyerhoff, Richard M Scearce, Damon F Ogburn, Brad Lockwood, Joy Pickeral, Masa Kuraoka, Kara Anasti, Joshua Eudailey, Amanda Eaton, Melissa Cooper, Kevin Wiehe, David C Montefiori, Georgia D Tomaras, Guido Ferrari, S Munir Alam, Hua-Xin Liao, Bette Korber, Feng Gao, Barton F Haynes
Antibodies that cross-react with multiple HIV-1 envelopes (Envs) are useful reagents for characterizing Env proteins and for soluble Env capture and purification assays. We previously reported ten murine monoclonal antibodies induced by group M consensus Env, CON-6 immunization. Each demonstrated broad cross-reactivity to recombinant Envs. Here we characterized the Env epitopes to which they bind. Seven mapped to linear epitopes in gp120, five at the Env N-terminus and two at the Env C-terminus. One antibody, 13D7, bound at the gp120 N-terminus (aa 30-42), reacted with HIV-1-infected CD4+ T cells, and when expressed in a human IgG1 backbone, mediated ADCC...
March 17, 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/28292718/latent-murine-leukemia-virus-infection-characterized-by-the-release-of-non-infectious-virions
#3
Stefano Boi, Erik Van Dis, Ethan J Hansen, Kyle Rosenke, Karin E Peterson, Morgan E Ferrell, Leonard H Evans
Clonal cell lines derived from cultures infected with a polytropic MuLV release vastly different levels of infectious virions ranging from undetectable to very high. Low producing clones release an overwhelming proportion of non-infectious virions containing retroviral RNA but deficient in the Env protein. Non-infectious virion production is not due to an inability of the cells to support infectious MuLV production or to an inherent replicative defectiveness of the proviruses. Reinfection of the lowest producing lines with the polytropic or an ecotropic MuLV results in enormous increases in the specific infectivity of the released virions...
March 11, 2017: Virology
https://www.readbyqxmd.com/read/28275375/a-comparative-phase-i-study-of-combination-homologous-subtype-c-dna-mva-and-env-gp140-protein-adjuvant-hiv-vaccines-in-two-immunization-regimes
#4
Sarah Joseph, Killian Quinn, Aldona Greenwood, Alethea V Cope, Paul F McKay, Peter J Hayes, Jakub T Kopycinski, Jill Gilmour, Aleisha N Miller, Christof Geldmacher, Yuka Nadai, Mohamed I M Ahmed, David C Montefiori, Len Dally, George Bouliotis, David J M Lewis, Roger Tatoud, Ralf Wagner, Mariano Esteban, Robin J Shattock, Sheena McCormack, Jonathan Weber
There remains an urgent need for a prophylactic HIV vaccine. We compared combined MVA and adjuvanted gp140 to sequential MVA/gp140 after DNA priming. We expected Env-specific CD4+ T-cells after DNA and MVA priming, and Env-binding antibodies in 100% individuals after boosting with gp140 and that combined vaccines would not compromise safety and might augment immunogenicity. Forty volunteers were primed three times with DNA plasmids encoding (CN54) env and (ZM96) gag-pol-nef at 0, 4 and 8 weeks then boosted with MVA-C (CN54 env and gag-pol-nef) and glucopyranosyl lipid adjuvant-aqueous formulation (GLA-AF) adjuvanted CN54gp140...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28257301/adjuvants-tailoring-humoral-immune-responses
#5
M Juliana McElrath
PURPOSE OF REVIEW: The development and availability of new-generation adjuvants beyond aluminum and emulsion formulations, together with a deeper understanding of the mechanistic role of adjuvant formulations in stimulating innate immunity and offer opportunities to improve candidate vaccine designs intended to protect against HIV-1 acquisition. RECENT FINDINGS: Currently, major efforts in vaccine development focus on improving prime-boost vaccine regimens to enhance efficacy beyond 31% observed in the RV144 phase 3 study and to develop a pathway to induce broadly reactive HIV neutralizing antibodies...
March 2, 2017: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/28250125/conformational-states-of-a-soluble-uncleaved-hiv-1-envelope-trimer
#6
Yuhang Liu, Junhua Pan, Yongfei Cai, Nikolaus Grigorieff, Stephen C Harrison, Bing Chen
HIV-1 envelope spike [Env; trimeric (gp160)3, cleaved to (gp120/gp41)3] induces membrane fusion, leading to viral entry. It is also the viral component targeted by neutralizing antibodies. Vaccine development requires production, in quantities suitable for clinical studies, of a recombinant form that resembles functional Env. HIV-1 gp140 trimers - the uncleaved ectodomains of (gp160)3 - from a few selected viral isolates adopt a compact conformation with many antigenic properties of native Env spikes. One is currently being evaluated in a clinical trial...
March 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28246356/differential-antibody-responses-to-conserved-hiv-1-neutralizing-epitopes-in-the-context-of-multivalent-scaffolds-and-native-like-gp140-trimers
#7
Charles D Morris, Parisa Azadnia, Natalia de Val, Nemil Vora, Andrew Honda, Erick Giang, Karen Saye-Francisco, Yushao Cheng, Xiaohe Lin, Colin J Mann, Jeffrey Tang, Devin Sok, Dennis R Burton, Mansun Law, Andrew B Ward, Linling He, Jiang Zhu
Broadly neutralizing antibodies (bNAbs) have provided valuable insights into the humoral immune response to HIV-1. While rationally designed epitope scaffolds and well-folded gp140 trimers have been proposed as vaccine antigens, a comparative understanding of their antibody responses has not yet been established. In this study, we probed antibody responses to the N332 supersite and the membrane-proximal external region (MPER) in the context of heterologous protein scaffolds and native-like gp140 trimers. Ferritin nanoparticles and fragment crystallizable (Fc) regions were utilized as multivalent carriers to display scaffold antigens with grafted N332 and MPER epitopes, respectively...
February 28, 2017: MBio
https://www.readbyqxmd.com/read/28223490/sequential-activation-of-the-three-protomers-in-the-moloney-murine-leukemia-virus-env
#8
Mathilda Sjöberg, Robin Löving, Birgitta Lindqvist, Henrik Garoff
Viral membrane fusion proteins of class I are trimers in which the protomeric unit is a complex of a surface subunit (SU) and a fusion active transmembrane subunit (TM). Here we have studied how the protomeric units of Moloney murine leukemia virus envelope protein (Env) are activated in relation to each other, sequentially or simultaneously. We followed the isomerization of the SU-TM disulfide and subsequent SU release from Env with biochemical methods and found that this early activation step occurred sequentially in the three protomers, generating two asymmetric oligomer intermediates according to the scheme (SU-TM)3 → (SU-TM)2TM → (SU-TM)TM2 → TM3 This was the case both when activation was triggered in vitro by depleting stabilizing Ca(2+) from solubilized Env and when viral Env was receptor triggered on rat XC cells...
March 7, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28213870/molecular-characterization-of-bovine-leukemia-virus-from-moldovan-dairy-cattle
#9
Aneta Pluta, Marzena Rola-Łuszczak, Piotr Kubiś, Svetlana Balov, Roman Moskalik, Bhudipa Choudhury, Jacek Kuźmak
Bovine leukemia virus (BLV) is the causative agent of enzootic bovine leukosis (EBL), a disease that has worldwide distribution. Whilst it has been eradicated in most of Western Europe and Scandinavia, it remains a problem in other regions, particularly Eastern Europe and South America. For this study, in 2013, 24 cattle from three farms in three regions of Moldova were screened by ELISA and nested PCR. Of these cattle, 14 which were PCR positive, and these were molecularly characterized based on the nucleotide sequence of the env gene and the deduced amino acid sequence of the encoded gp51 protein...
February 17, 2017: Archives of Virology
https://www.readbyqxmd.com/read/28209172/evaluation-of-the-contribution-of-the-transmembrane-region-to-the-ectodomain-conformation-of-the-human-immunodeficiency-virus-hiv-1-envelope-glycoprotein
#10
Hanh T Nguyen, Navid Madani, Haitao Ding, Emerald Elder, Amy Princiotto, Christopher Gu, Patrice Darby, James Alin, Alon Herschhorn, John C Kappes, Youdong Mao, Joseph G Sodroski
BACKGROUND: The human immunodeficiency virus (HIV-1) envelope glycoprotein (Env), a Type 1 transmembrane protein, assembles into a trimeric spike complex that mediates virus entry into host cells. The high potential energy of the metastable, unliganded Env trimer is maintained by multiple non-covalent contacts among the gp120 exterior and gp41 transmembrane Env subunits. Structural studies suggest that the gp41 transmembrane region forms a left-handed coiled coil that contributes to the Env trimer interprotomer contacts...
February 16, 2017: Virology Journal
https://www.readbyqxmd.com/read/28207489/b-cell-abnormalities-and-impact-on-antibody-response-in-hiv-infection
#11
Alessandra Noto, Giuseppe Pantaleo
PURPOSE OF REVIEW: The purpose of the present review is to provide an update on the current development in the field of broadly neutralizing antibodies (bNabs) and their potential use in the prevention and therapeutic settings, and an evaluation of the B-cell abnormalities that may impair antibody responses in HIV infection. RECENT FINDINGS: Major advances have been achieved in the characterization of bNabs directed against different vulnerable regions of HIV Envelope (Env)...
February 15, 2017: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/28207486/particle-based-delivery-of-the-hiv-envelope-protein
#12
Benedikt Asbach, Ralf Wagner
PURPOSE OF REVIEW: A major focus in HIV vaccine research is the development of suitable antigens that elicit broadly neutralizing antibody responses targeting HIV's envelope protein (Env). Delivery of Env in a repetitive manner on particle-based carriers allows higher avidity interactions and is therefore expected to efficiently engage B cells, thus leading to affinity maturation that results in superior antibody responses characterized by improved breadth, potency, and durability. This review summarizes current work that is evaluating diverse types of such particulate carriers for Env delivery...
February 15, 2017: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/28202756/a-glycosylation-benchmark-profile-for-hiv-1-envelope-glycoprotein-production-based-on-eleven-env-trimers
#13
Eden P Go, Haitao Ding, Shijian Zhang, Rajesh P Ringe, Nathan Nicely, David Hua, Robert T Steinbock, Michael Golabek, James Alin, S Munir Alam, Albert Cupo, Barton F Haynes, John C Kappes, John P Moore, Joseph G Sodroski, Heather Desaire
HIV-1 envelope glycoprotein (Env) glycosylation is important because individual glycans are components of multiple broadly neutralizing antibody epitopes, while shielding other sites that might otherwise be immunogenic. The glycosylation on Env is influenced by a variety of factors, including the genotype of the protein, the cell line used for its expression, and the details of the construct design. Here, we used a mass spectrometry-based approach to map the complete glycosylation profile at every site in multiple HIV-1 Env trimers, accomplishing two goals: 1) We determined which glycosylation sites contain conserved glycan profiles across many trimeric Envs...
February 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28202751/superiority-in-rhesus-macaques-of-targeting-hiv-1-env-gp140-to-cd40-versus-lox-1-in-combination-with-replication-competent-nyvac-kc-for-induction-of-env-specific-antibody-and-t-cell-responses
#14
Gerard Zurawski, Xiaoying Shen, Sandra Zurawski, Georgia D Tomaras, David C Montefiori, Mario Roederer, Guido Ferrari, Christine Lacabaratz, Peter Klucar, Zhiqing Wang, Kathryn E Foulds, Shing-Fen Kao, Xuesong Yu, Alicia Sato, Nicole L Yates, Celia LaBranche, Sherry Stanfield-Oakley, Karen Kibler, Bertram Jacobs, Andres Salazar, Steve Self, Jimmy Fulp, Raphael Gottardo, Lindsey Galmin, Deborah Weiss, Anthony Cristillo, Giuseppe Pantaleo, Yves Levy
We compared the HIV-1-specific immune responses generated by targeting HIV-1 envelope protein (Env gp140) to either CD40 or LOX-1, two endocytic receptors on dendritic cells (DCs), in Rhesus macaques primed with a poxvirus vector (NYVAC-KC) expressing Env gp140. The DC-targeting vaccines, humanized recombinant monoclonal antibodies fused to Env gp140, were administered as a boost with poly ICLC adjuvant either alone or co-administered with the NYVAC-KC vector. All the DC-targeting vaccine administrations with poly ICLC increased the low-level serum anti-Env IgG responses elicited by NYVAC-KC priming significantly more (up to P =0...
February 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28196510/partial-hiv-c2v3-envelope-sequence-analysis-reveals-association-of-coreceptor-tropism-envelope-glycosylation-and-viral-genotypic-variability-among-kenyan-patients-on-haart
#15
Rose C Kitawi, Carol W Hunja, Rashid Aman, Bernhards R Ogutu, Anne W T Muigai, Gilbert O Kokwaro, Washingtone Ochieng
BACKGROUND: HIV-1 is highly variable genetically and at protein level, a property it uses to subvert antiviral immunity and treatment. The aim of this study was to assess if HIV subtype differences were associated with variations in glycosylation patterns and co-receptor tropism among HAART patients experiencing different virologic treatment outcomes. METHODS: A total of 118 HIV env C2V3 sequence isolates generated previously from 59 Kenyan patients receiving highly active antiretroviral therapy (HAART) were examined for tropism and glycosylation patterns...
February 14, 2017: Virology Journal
https://www.readbyqxmd.com/read/28194372/mir-34b-5p-suppresses-melanoma-differentiation-associated-gene-5-mda5-signaling-pathway-to-promote-avian-leukosis-virus-subgroup-j-alv-j-infected-cells-proliferaction-and-alv-j-replication
#16
Zhenhui Li, Qingbin Luo, Haiping Xu, Ming Zheng, Bahareldin Ali Abdalla, Min Feng, Bolin Cai, Xiaocui Zhang, Qinghua Nie, Xiquan Zhang
Avian leukosis virus subgroup J (ALV-J) is an oncogenic retrovirus that has a similar replication cycle to multiple viruses and therefore can be used as a model system for viral entry into host cells. However, there are few reports on the genes or microRNAs (miRNAs) that are responsible for the replication of ALV-J. Our previous miRNA and RNA sequencing data showed that the expression of miR-34b-5p was significantly upregulated in ALV-J-infected chicken spleens compared to non-infected chicken spleens, but melanoma differentiation-associated gene 5 (MDA5) had the opposite expression pattern...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28179536/hiv-aids-vaccine-candidates-based-on-replication-competent-recombinant-poxvirus-nyvac-c-kc-expressing-trimeric-gp140-and-gag-derived-vlps-or-lacking-the-viral-molecule-b19-that-inhibits-type-i-interferon-activate-relevant-hiv-1-specific-b-and-t-cell-immune
#17
Juan García-Arriaza, Beatriz Perdiguero, Jonathan L Heeney, Michael S Seaman, David C Montefiori, Nicole L Yates, Georgia D Tomaras, Guido Ferrari, Kathryn E Foulds, Mario Roederer, Steven G Self, Bhavesh Borate, Raphael Gottardo, Sanjay Phogat, Jim Tartaglia, Susan W Barnett, Brian Burke, Anthony D Cristillo, Deborah E Weiss, Carter Lee, Karen V Kibler, Bertram L Jacobs, Ralf Wagner, Song Ding, Giuseppe Pantaleo, Mariano Esteban
The non-replicating attenuated poxvirus vector NYVAC expressing clade C(CN54) HIV-1 Env(gp120), Gag-Pol-Nef antigens (NYVAC-C) showed in phase I clinical trials limited immunogenicity. To enhance the capacity of the NYVAC vector to trigger broad humoral responses and a more balanced activation of CD4(+) and CD8(+) T cells, here we compared the HIV-1-specific immunogenicity elicited in non-human primates immunized with two replicating NYVAC vectors that have been modified by the insertion of K1L and C7L vaccinia viral host-range genes and express clade C(ZM96) trimeric HIV-1 gp140 protein or a Gag(ZM96)-Pol-Nef(CN54) polyprotein as Gag-derived virus-like particles (termed NYVAC-C-KC)...
February 8, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28179429/serinc5-inhibits-hiv-1-fusion-pore-formation-by-promoting-functional-inactivation-of-envelope-glycoproteins
#18
Chetan Sood, Mariana Marin, Ajit Chande, Massimo Pizzato, Gregory B Melikyan
The host proteins, SERINC3 and SERINC5, have been recently shown to incorporate into HIV-1 particles and compromise their ability to fuse with target cells - an effect that is antagonized by the viral Nef protein. Env glycoproteins from different HIV-1 isolates exhibit a broad range of sensitivity to SERINC-mediated restriction, and the mechanism by which SERINCs interfere with HIV-1 fusion remains unclear. Here, we show that incorporation of SERINC5 into virions in the absence of Nef inhibits the formation of small fusion pores between viruses and cells...
February 8, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28167948/mouse-liver-sinusoidal-endothelium-eliminates-hiv-like-particles-from-blood-at-a-rate-of-100-million-per-minute-by-a-second-order-kinetic-process
#19
Jessica M Mates, Zhili Yao, Alana M Cheplowitz, Ozan Suer, Gary S Phillips, Jesse J Kwiek, Murugesan V S Rajaram, Jonghan Kim, John M Robinson, Latha P Ganesan, Clark L Anderson
We crafted human immunodeficiency virus (HIV)-like particles of diameter about 140 nm, which expressed two major HIV-1 proteins, namely, env and gag gene products, and used this reagent to simulate the rate of decay of HIV from the blood stream of BALB/c male mice. We found that most (~90%) of the particles were eliminated (cleared) from the blood by the liver sinusoidal endothelial cells (LSECs), the remainder from Kupffer cells; suggesting that LSECs are the major liver scavengers for HIV clearance from blood...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28166800/a-purine-rich-element-in-foamy-virus-pol-regulates-env-splicing-and-gag-pol-expression
#20
Rebecca Moschall, Sarah Denk, Steffen Erkelenz, Christian Schenk, Heiner Schaal, Jochen Bodem
BACKGROUND: The foamy viral genome encodes four central purine-rich elements localized in the integrase-coding region of pol. Previously, we have shown that the first two of these RNA elements (A and B) are required for protease dimerization and activation. The D element functions as internal polypurine tract during reverse transcription. Peters et al., described the third element (C) as essential for gag expression suggesting that it might serve as an RNA export element for the unspliced genomic transcript...
February 6, 2017: Retrovirology
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