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https://www.readbyqxmd.com/read/28539451/reducing-v3-antigenicity-and-immunogenicity-on-soluble-native-like-hiv-1-env-sosip-trimers
#1
Rajesh P Ringe, Gabriel Ozorowski, Kimmo Rantalainen, Weston B Struwe, Katie Matthews, Jonathan L Torres, Anila Yasmeen, Christopher A Cottrell, Thomas J Ketas, Celia C LaBranche, David C Montefiori, Albert Cupo, Max Crispin, Ian A Wilson, Andrew B Ward, Rogier W Sanders, P J Klasse, John P Moore
Native-like trimers of the SOSIP design are being developed as immunogens in human immunodeficiency virus type 1 (HIV-1) vaccine development programs. These trimers display the epitopes for multiple broadly neutralizing antibodies (bNAbs), but can also expose binding sites for some types of non-neutralizing antibodies (non-NAbs). Among the latter are epitopes in the gp120 V3 region that are highly immunogenic when SOSIP trimers are evaluated in animal models. It is presently uncertain whether antibodies against V3 can interfere with the induction of NAbs, but there are good arguments in favor of suppressing such "off-target" immune responses...
May 24, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28538165/the-complexity-in-herpesvirus-entry
#2
REVIEW
Karthik Sathiyamoorthy, Jia Chen, Richard Longnecker, Theodore S Jardetzky
Enveloped viruses have evolved diverse transmembrane proteins and protein complexes to enable host cell entry by regulating and activating membrane fusion in a target cell-specific manner. In general terms, the entry process requires a receptor binding step, an activation step and a membrane fusion step, which can be encoded within a single viral protein or distributed among multiple viral proteins. HIV and influenza virus, for example, encode all of these functions in a single trimeric glycoprotein, HIV env or influenza virus hemagglutinin (HA)...
May 21, 2017: Current Opinion in Virology
https://www.readbyqxmd.com/read/28490736/extracellular-vesicles-carry-hiv-env-and-facilitate-hiv-infection-of-human-lymphoid-tissue
#3
Anush Arakelyan, Wendy Fitzgerald, Sonia Zicari, Christophe Vanpouille, Leonid Margolis
Cells productively infected with HIV-1 release virions along with extracellular vesicles (EVs) whose biogenesis, size, and physical properties resemble those of retroviruses. Here, we found that a significant number of EVs (exosomes) released by HIV-1 infected cells carry gp120 (Env), a viral protein that mediates virus attachment and fusion to target cells, and also facilitates HIV infection in various indirect ways. Depletion of viral preparations of EVs, in particular of those that carry gp120, decreases viral infection of human lymphoid tissue ex vivo...
May 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28490588/induction-of-a-tier-1-like-phenotype-in-diverse-tier-2-isolates-by-agents-that-guide-hiv-1-env-to-perturbation-sensitive-non-native-states
#4
Jacklyn Johnson, Yinjie Zhai, Hamid Salimi, Nicole Espy, Noah Eichelberger, Orlando DeLeon, Yunxia O'Malley, Joel Courter, Amos B Smith, Navid Madani, Joseph Sodroski, Hillel Haim
The envelope glycoproteins (Envs) on the surface of HIV-1 particles are targeted by host antibodies. Primary HIV-1 isolates demonstrate different global sensitivities to antibody neutralization; Tier-1 isolates are sensitive whereas Tier-2 isolates are more resistant. Single-site mutations in Env can convert Tier-2 into Tier-1-like viruses. We hypothesized that such global change in neutralization sensitivity results from weakening of intra-molecular interactions that maintain Env integrity. Three strategies commonly applied to perturb protein structure were tested for their effect on global neutralization sensitivity; exposure to low temperature, Env-activating ligands and a chaotropic agent...
May 10, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28490585/crosslinking-of-a-cd4-mimetic-miniprotein-with-hiv-1-env-gp140-alters-kinetics-and-specificities-of-antibody-responses-against-hiv-1-env-in-macaques
#5
Xiaoying Shen, Willy M Bogers, Nicole L Yates, Guido Ferrari, Antu K Dey, William T Williams, Frederick H Jaeger, Kevin Wiehe, Sheetal Sawant, S Munir Alam, Celia C LaBranche, David C Montefiori, Loic Martin, Indresh Srivastava, Jonathan Heeney, Susan W Barnett, Georgia D Tomaras
Evaluation of the epitope specificities, location (systemic, mucosal) and effector function of antibodies elicited by novel HIV-1 immunogens engineered to improve exposure of specific epitopes is critical for HIV-1 vaccine development. Utilizing an array of humoral assays, we evaluated the magnitude, epitope specificity, avidity and function of systemic and mucosal immune responses elicited by a vaccine regimen containing Env cross-linked to a CD4 mimetic miniprotein (gp140-M64U1) in rhesus macaques. Crosslinking of gp140 Env with M64U1 resulted in an earlier increase in both the magnitude and avidity of the IgG binding response compared to Env protein alone...
May 10, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28483193/expression-of-complete-siv-p27-gag-and-hiv-gp120-engineered-outer-domains-targeted-by-broadly-neutralizing-antibodies-in-live-rubella-vectors
#6
Konstantin Virnik, Edmund Nesti, Cody Dail, Max Hockenbury, Yisheng Ni, Barbara K Felber, William R Schief, Ira Berkower
Infection with HIV or SIV often elicits a potent immune response to viral antigens. This includes T cells and antibodies specific for Gag and Env antigens. In contrast, when given as a vaccine, the same antigens have been weak immunogens, unable to elicit antibodies with comparable titer, durability, or neutralizing activity. We have used the live attenuated rubella vaccine strain RA27/3 as a viral vector to express HIV and SIV antigens. By mimicking an HIV infection, these vectors could elicit stronger and more durable immunity to HIV antigens...
May 31, 2017: Vaccine
https://www.readbyqxmd.com/read/28458735/features-of-maternal-hiv-1-associated-with-lack-of-vertical-transmission
#7
REVIEW
Nafees Ahmad, Aamir N Ahmad, Shahid N Ahmad
HIV-1 is transmitted from mother-to-child (vertical transmission) at an estimated rate of approximately 30% without any antiretroviral therapy (ART). However, administration of ART during pregnancy considerably diminishes the rate of mother-to-child transmission of HIV-1, which has become a standard of perinatal care in HIV-infected pregnant females in developed countries. Moreover, a majority of children born to HIV-infected mothers are uninfected without any ART. In addition, characteristics of HIV-1 and/or cellular factors in the mothers may play a role in influencing or preventing vertical transmission...
2017: Open Virology Journal
https://www.readbyqxmd.com/read/28457706/a-versatile-tool-for-live-cell-imaging-and-super-resolution-nanoscopy-studies-of-hiv-1-env-distribution-and-mobility
#8
Volkan Sakin, Janina Hanne, Jessica Dunder, Maria Anders-Össwein, Vibor Laketa, Ivana Nikić, Hans-Georg Kräusslich, Edward A Lemke, Barbara Müller
The envelope glycoproteins (Env) of HIV-1 mediate cell entry through fusion of the viral envelope with a target cell membrane. Intramembrane mobility and clustering of Env trimers at the viral budding site are essential for its function. Previous live-cell and super-resolution microscopy studies were limited by lack of a functional fluorescent Env derivative, requiring antibody labeling for detection. Introduction of a bio-orthogonal amino acid by genetic code expansion, combined with click chemistry, offers novel possibilities for site-specific, minimally invasive labeling...
May 18, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28449719/interference-of-retroviral-envelope-with-vaccine-induced-cd8-t-cell-responses-is-relieved-by-co-administration-of-cytokine-encoding-vectors
#9
Nadine Bongard, Dennis Lapuente, Sonja Windmann, Ulf Dittmer, Matthias Tenbusch, Wibke Bayer
BACKGROUND: Retroviral envelope (Env) proteins are known to exhibit immunosuppressive properties, which become apparent not only in retroviral infections, but also in gene-based immunizations using retroviral immunogens, where envelope interferes with the induction of CD8(+) T cell responses towards another, simultaneously or subsequently delivered, immunogen. RESULTS: In the Friend retrovirus mouse model, immunization with a plasmid encoding the Friend murine leukemia virus (F-MuLV) Leader-Gag protein resulted in induction of a strong GagL85-93-specific CD8(+) T cell response, while the response was completely abrogated by co-immunization with an F-MuLV Env-encoding plasmid...
April 27, 2017: Retrovirology
https://www.readbyqxmd.com/read/28446665/dense-array-of-spikes-on-hiv-1-virion-particles
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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