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https://www.readbyqxmd.com/read/28446665/dense-array-of-spikes-on-hiv-1-virion-particles
#1
Armando Stano, Daniel P Leaman, Arthur S Kim, Lei Zhang, Ludovic Autin, Jidnyasa Ingale, Syna K Gift, Jared Truong, Richard T Wyatt, Arthur J Olson, Michael B Zwick
HIV-1 is rare among viruses for having a low number of envelope glycoprotein (Env) spikes per virion, i.e. ∼7-14. This exceptional feature has been associated with avoidance of humoral immunity, i.e. B cell activation and antibody neutralization. Virus-like particles (VLPs) with increased density of Env are being pursued for vaccine development; however these typically require protein engineering that alters Env structure. Here, we used instead a strategy that targets the producer cell. We employed fluorescence activated cell sorting (FACS) to sort for cells that are recognized by trimer crossreactive broadly neutralizing antibody (bnAb) and not by non-neutralizing antibodies...
April 26, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28446609/glycosylation-of-the-core-of-the-hiv-1-envelope-subunit-protein-gp120-is-not-required-for-native-trimer-formation-or-viral-infectivity
#2
Ujjwal Rathore, Piyali Saha, Sannula Kesavardhana, Aditya Arun Kumar, Rohini Datta, Sivasankar Devanarayanan, Raksha Das, John R Mascola, Raghavan Varadarajan
The gp120 subunit of HIV-1 envelope (Env) protein is heavily glycosylated at approximately 25 glycosylation sites, of which ~7-8 are located in the V1/V2 and V3 variable loops and the others in the remaining core gp120 region. Glycans partially shield Env from recognition by the host immune system and also are believed to be indispensable for proper folding of gp120 and for viral infectivity. Previous attempts to alter glycosylation sites in Env typically involved mutating the glycosylated asparagine residues to structurally similar glutamines or to alanines...
April 26, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28445724/quantification-of-the-impact-of-the-hiv-1-glycan-shield-on-antibody-elicitation
#3
Tongqing Zhou, Nicole A Doria-Rose, Cheng Cheng, Guillaume B E Stewart-Jones, Gwo-Yu Chuang, Michael Chambers, Aliaksandr Druz, Hui Geng, Krisha McKee, Young Do Kwon, Sijy O'Dell, Mallika Sastry, Stephen D Schmidt, Kai Xu, Lei Chen, Rita E Chen, Mark K Louder, Marie Pancera, Timothy G Wanninger, Baoshan Zhang, Anqi Zheng, S Katie Farney, Kathryn E Foulds, Ivelin S Georgiev, M Gordon Joyce, Thomas Lemmin, Sandeep Narpala, Reda Rawi, Cinque Soto, John-Paul Todd, Chen-Hsiang Shen, Yaroslav Tsybovsky, Yongping Yang, Peng Zhao, Barton F Haynes, Leonidas Stamatatos, Michael Tiemeyer, Lance Wells, Diana G Scorpio, Lawrence Shapiro, Adrian B McDermott, John R Mascola, Peter D Kwong
While the HIV-1-glycan shield is known to shelter Env from the humoral immune response, its quantitative impact on antibody elicitation has been unclear. Here, we use targeted deglycosylation to measure the impact of the glycan shield on elicitation of antibodies against the CD4 supersite. We engineered diverse Env trimers with select glycans removed proximal to the CD4 supersite, characterized their structures and glycosylation, and immunized guinea pigs and rhesus macaques. Immunizations yielded little neutralization against wild-type viruses but potent CD4-supersite neutralization (titers 1: >1,000,000 against four-glycan-deleted autologous viruses with over 90% breadth against four-glycan-deleted heterologous strains exhibiting tier 2 neutralization character)...
April 25, 2017: Cell Reports
https://www.readbyqxmd.com/read/28424455/flow-virometry-analysis-of-envelope-glycoprotein-conformations-on-individual-hiv-virions
#4
Anush Arakelyan, Wendy Fitzgerald, Deborah F King, Paul Rogers, Hannah M Cheeseman, Jean-Charles Grivel, Robin J Shattock, Leonid Margolis
HIV-1 envelope proteins (Envs) play a critical role in HIV infection. In a correct trimeric conformation, Env mediates virus-cell binding and fusion. Malfunctioning of this machinery renders virions incapable of infecting cells. Each HIV-1 virion carries 10-14 Envs, and therefore a defective Env may not necessarily render a HIV virion non-infectious, since other Env on the same virion may still be functional. Alternatively, it is possible that on a given virion either all the spikes are defective or all are functional...
April 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28424281/distinct-roles-of-vaccinia-virus-nf-kb-inhibitor-proteins-a52-b15-and-k7-in-the-immune-response
#5
Mauro Di Pilato, Ernesto Mejías-Pérez, Carlos Oscar S Sorzano, Mariano Esteban
Poxviruses use a complex strategy to escape immune control, by expressing immunomodulatory proteins that could limit their use as vaccine vectors. To test the role of poxvirus NF-κB pathway inhibitors A52, B15 and K7 in immunity, we deleted their genes in a NYVAC vaccinia virus strain that expresses HIV-1 clade C antigens. After infection of mice, ablation of A52R, B15R and K7R increased dendritic cell, natural killer cell and neutrophil migration as well as chemokine/cytokine expression. Revertant viruses for these genes confirmed their role in inhibiting the innate immune system...
April 19, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28422790/particle-based-delivery-of-the-hiv-envelope-protein
#6
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...
May 2017: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/28422784/b-cell-abnormalities-and-impact-on-antibody-response-in-hiv-infection
#7
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)...
May 2017: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/28419107/characterization-of-a-transgenic-mouse-model-exhibiting-spontaneous-lung-adenocarcinomas-with-a-metastatic-phenotype
#8
Hsuen-Wen Chang, Zih-Miao Lin, Min-Ju Wu, Li-Yu Wang, Yen-Hung Chow, Shih Sheng Jiang, Hui-Ju Ch'ang, Vincent Hs Chang
Developing lung cancer in mouse models that display similarities of both phenotype and genotype will undoubtedly provide further and better insights into lung tumor biology. Moreover, a high degree of pathophysiological similarity between lung tumors from mouse models and their human counterparts will make it possible to use these mouse models for preclinical tests. Ovine pulmonary adenocarcinomas (OPAs) present the same symptoms as adenocarcinomas in humans and are caused by a betaretrovirus. OPAs have served as an exquisite model of carcinogenesis for human lung adenocarcinomas...
2017: PloS One
https://www.readbyqxmd.com/read/28404572/an-hiv-envelope-gp120-fc-fusion-protein-elicits-effector-antibody-responses-in-rhesus-macaques
#9
Zhanna Shubin, Weizhong Li, Bhawna Poonia, Guido Ferrari, Celia LaBranche, David Montefiori, Xiaoping Zhu, C David Pauza
A goal for HIV prevention programs is to develop safe and effective vaccines that elicit durable and broadly protective antibodies. Many vaccine programs focus on the immune responses to critical epitopes in the gp120 portion of HIV envelope glycoprotein (Env) and seek to improve the quality and quantity of antibodies by altering the sequence, conformation, oligomerization or glycosylation of gp120 to activate appropriate germline B cells and mimic the subsequent maturation pathways seen in infected individuals...
April 12, 2017: Clinical and Vaccine Immunology: CVI
https://www.readbyqxmd.com/read/28397686/co-option-of-an-endogenous-retrovirus-envelope-for-host-defense-in-hominid-ancestors
#10
Daniel Blanco-Melo, Robert J Gifford, Paul D Bieniasz
Endogenous retroviral sequences provide a molecular fossil record of ancient infections whose analysis might illuminate mechanisms of viral extinction. A close relative of gammaretroviruses, HERV-T, circulated in primates for ~25 million years (MY) before apparent extinction within the past ~8 MY. Construction of a near-complete catalog of HERV-T fossils in primate genomes allowed us to estimate a ~32 MY old ancestral sequence and reconstruct a functional envelope protein (ancHTenv) that could support infection of a pseudotyped modern gammaretrovirus...
April 11, 2017: ELife
https://www.readbyqxmd.com/read/28390972/targeting-cell-surface-hiv-1-env-protein-to-suppress-infectious-virus-formation
#11
Arangassery Rosemary Bastian, Charles G Ang, Kantharaju Kamanna, Farida Shaheen, Yu-Hung Huang, Karyn McFadden, Caitlin Duffy, Lauren D Bailey, Ramalingam Venkat Kalyana Sundaram, Irwin Chaiken
HIV-1 Env protein is essential for host cell entry, and targeting Env remains an important antiretroviral strategy. We previously found that a peptide triazole thiol KR13 and its gold nanoparticle conjugate AuNP-KR13 directly and irreversibly inactivate the virus by targeting the Env protein, leading to virus gp120 shedding, membrane disruption and p24 capsid protein release. Here, we examined the consequences of targeting cell-surface Env with the virus inactivators. We found that both agents led to formation of non-infectious virus from transiently transfected HEK293T cells...
April 6, 2017: Virus Research
https://www.readbyqxmd.com/read/28388673/proteolysis-of-mature-hiv-1-p6-gag-protein-by-the-insulin-degrading-enzyme-ide-regulates-virus-replication-in-an-env-dependent-manner
#12
Friedrich Hahn, Adrian Schmalen, Christian Setz, Melanie Friedrich, Stefan Schlößer, Julia Kölle, Robert Spranger, Pia Rauch, Kirsten Fraedrich, Tatjana Reif, Julia Karius-Fischer, Ashok Balasubramanyam, Petra Henklein, Torgils Fossen, Ulrich Schubert
There is a significantly higher risk for type II diabetes in HIV-1 carriers, albeit the molecular mechanism for this HIV-related pathology remains enigmatic. The 52 amino acid HIV-1 p6 Gag protein is synthesized as the C-terminal part of the Gag polyprotein Pr55. In this context, p6 promotes virus release by its two late (L-) domains, and facilitates the incorporation of the viral accessory protein Vpr. However, the function of p6 in its mature form, after proteolytic release from Gag, has not been investigated yet...
2017: PloS One
https://www.readbyqxmd.com/read/28381572/improving-the-expression-and-purification-of-soluble-recombinant-native-like-hiv-1-envelope-glycoprotein-trimers-by-targeted-sequence-changes
#13
Rajesh P Ringe, Gabriel Ozorowski, Anila Yasmeen, Albert Cupo, Victor M Cruz Portillo, Pavel Pugach, Michael Golabek, Kimmo Rantalainen, Lauren G Holden, Christopher A Cottrell, Ian A Wilson, Rogier W Sanders, Andrew B Ward, P J Klasse, John P Moore
Soluble, recombinant native-like envelope glycoprotein (Env) trimers of various human immunodeficiency virus type 1 (HIV-1) genotypes are being developed for structural studies and as vaccine candidates aimed at the induction of broadly neutralizing antibodies (bNAbs). The prototypic design is designated SOSIP.664, but many HIV-1 env genes do not yield fully native-like trimers efficiently. One such env gene is CZA97.012 from a neutralization-resistant (Tier-2) clade C virus. As appropriately purified, native-like CZA97...
April 5, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28374253/display-of-hiv-1-envelope-protein-on-lambda-phage-scaffold-as-a-vaccine-platform
#14
Jonelle L Mattiacio, Matt Brewer, Stephen Dewhurst
The generation of a strong antibody response to target antigens is a major goal for vaccine development. Here we describe the display of the human immunodeficiency virus (HIV) envelope spike protein (Env) on a virus-like scaffold provided by the lambda phage capsid. Phage vectors, in general, have advantages over mammalian virus vectors due to their genetic tractability, inexpensive production, suitability for scale-up, as well as their physical stability, making them an attractive vaccine platform.
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28363124/structural-principles-controlling-hiv-envelope-glycosylation
#15
REVIEW
Anna-Janina Behrens, Max Crispin
The heavily glycosylated, trimeric HIV-1 envelope (Env) protein is the sole viral protein exposed on the HIV-1 virion surface and is thus a main focus of antibody-mediated vaccine development. Dense glycosylation at the outer domain of Env constrains normal enzymatic processing, stalling the glycans at immature oligomannose-type structures. Furthermore, native trimerization imposes additional steric constraints, which generate an extensive 'trimer-induced mannose patch'. Importantly, the immature glycans present a highly conserved feature of the virus that is targeted by broadly neutralizing antibodies...
March 28, 2017: Current Opinion in Structural Biology
https://www.readbyqxmd.com/read/28355125/epitope-mapping-of-the-antibody-response-against-the-envelope-proteins-of-the-feline-foamy-virus
#16
Michael Mühle, Anne Bleiholder, Martin Löchelt, Joachim Denner
Foamy viruses (FV) are retroviruses that infect several species without pathological signs, but induce substantial antibody responses in the infected host. In the case of feline FV (FFV), antibodies against Gag, Bet, and Env have been used to indicate infection; however, it is unclear whether the response to specific epitopes correlates with immunity. Here, we investigated the epitope specificity of antibodies targeting the Env protein using peptide microarrays. Sera from naturally and experimentally FFV-infected cats and pumas and from rats immunized with FFV Env expression plasmids were analyzed...
March 29, 2017: Viral Immunology
https://www.readbyqxmd.com/read/28348411/global-site-specific-n-glycosylation-analysis-of-hiv-envelope-glycoprotein
#17
Liwei Cao, Jolene K Diedrich, Daniel W Kulp, Matthias Pauthner, Lin He, Sung-Kyu Robin Park, Devin Sok, Ching Yao Su, Claire M Delahunty, Sergey Menis, Raiees Andrabi, Javier Guenaga, Erik Georgeson, Michael Kubitz, Yumiko Adachi, Dennis R Burton, William R Schief, John R Yates Iii, James C Paulson
HIV-1 envelope glycoprotein (Env) is the sole target for broadly neutralizing antibodies (bnAbs) and the focus for design of an antibody-based HIV vaccine. The Env trimer is covered by ∼90N-linked glycans, which shield the underlying protein from immune surveillance. bNAbs to HIV develop during infection, with many showing dependence on glycans for binding to Env. The ability to routinely assess the glycan type at each glycosylation site may facilitate design of improved vaccine candidates. Here we present a general mass spectrometry-based proteomics strategy that uses specific endoglycosidases to introduce mass signatures that distinguish peptide glycosites that are unoccupied or occupied by high-mannose/hybrid or complex-type glycans...
March 28, 2017: Nature Communications
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
#18
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
#19
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
#20
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...
June 2017: Virology
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