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https://www.readbyqxmd.com/read/28651004/a-human-endogenous-retrovirus-derived-gene-that-can-contribute-to-oncogenesis-by-activating-the-erk-pathway-and-inducing-migration-and-invasion
#1
Cécile Lemaître, Jhen Tsang, Caroline Bireau, Thierry Heidmann, Marie Dewannieux
Endogenous retroviruses are cellular genes of retroviral origin captured by their host during the course of evolution and represent around 8% of the human genome. Although most are defective and transcriptionally silenced, some are still able to generate retroviral-like particles and proteins. Among these, the HERV-K(HML2) family is remarkable since its members have amplified relatively recently and many of them still have full length coding genes. Furthermore, they are induced in cancers, especially in melanoma, breast cancer and germ cell tumours, where viral particles, as well as the envelope protein (Env), can be detected...
June 26, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28639221/hbv-x-protein-induces-overexpression-of-herv-w-env-through-nf-%C3%AE%C2%BAb-in-hepg2-cells
#2
Cong Liu, Lijuan Liu, Xiuling Wang, Youyi Liu, Miao Wang, Fan Zhu
Human endogenous retrovirus W family (HERV-W) envelope (env) at chromosome 7 is highly expressed in the placenta and possesses fusogenic activity in trophoblast development. HERV-W env has been found to be overexpressed in some cancers and immune diseases. Viral transactivators can induce the overexpression of HERV-W env in human cell lines. Hepatitis B virus X protein (HBx) is believed to be a multifunctional oncogenic protein. Here, we reported that HBx could increase the promoter activity of HERV-W env and upregulate the mRNA levels of non-spliced and spliced HERV-W env and also its protein in human hepatoma HepG2 cells...
June 20, 2017: Virus Genes
https://www.readbyqxmd.com/read/28624214/further-characterization-of-the-bifunctional-hiv-entry-inhibitor-scd4-fit45
#3
Alexander Falkenhagen, Sadhna Joshi
HIV entry into target cells is a highly sequential and time-sensitive process. In recent years, potent HIV Env-targeting antibodies, such as VRC01, have been identified. However, antibodies bind only to a single epitope, and mutations that confer resistance to antibody-mediated inhibition of HIV entry have been detected. In contrast, HIV cannot escape from binding to soluble CD4 (sCD4) without a fitness disadvantage. sCD4 has the unique ability to induce conformational changes within the HIV envelope glycoproteins (Env) that allow fusion inhibitors to bind...
June 16, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28620613/evidence-of-divergent-amino-acid-usage-in-comparative-analyses-of-r5-and-x4-associated-hiv-1-vpr-sequences
#4
Gregory C Antell, Will Dampier, Benjamas Aiamkitsumrit, Michael R Nonnemacher, Vanessa Pirrone, Wen Zhong, Katherine Kercher, Shendra Passic, Jean Williams, Yucheng Liu, Tony James, Jeffrey M Jacobson, Zsofia Szep, Brian Wigdahl, Fred C Krebs
Vpr is an HIV-1 accessory protein that plays numerous roles during viral replication, and some of which are cell type dependent. To test the hypothesis that HIV-1 tropism extends beyond the envelope into the vpr gene, studies were performed to identify the associations between coreceptor usage and Vpr variation in HIV-1-infected patients. Colinear HIV-1 Env-V3 and Vpr amino acid sequences were obtained from the LANL HIV-1 sequence database and from well-suppressed patients in the Drexel/Temple Medicine CNS AIDS Research and Eradication Study (CARES) Cohort...
2017: International Journal of Genomics
https://www.readbyqxmd.com/read/28615419/dimeric-fc%C3%AE-receptor-enzyme-linked-immunosorbent-assay-to-study-hiv-specific-antibodies-a-new-look-into-breadth-of-fc%C3%AE-receptor-antibodies-induced-by-the-rv144-vaccine-trial
#5
Milla R McLean, Vijaya Madhavi, Bruce D Wines, P Mark Hogarth, Amy W Chung, Stephen J Kent
Ab-dependent cellular cytotoxicity (ADCC) responses are of growing interest in the HIV vaccine field but current cell-based assays are usually difficult to reproduce across laboratories. We developed an ELISA and multiplex assay to model the cross-linking of Fcγ receptors (FcγR) by Abs, which is required to initiate an ADCC response. Our FcγR dimer ELISA readily detected Abs in samples from two separate cohorts of the partially efficacious Thai RV144 HIV vaccine efficacy trial. The FcγR dimer-binding Abs induced by the RV144 regimen correlated well with a functional measure of ADCC as well as IgG subclasses...
June 14, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28615199/impaired-downregulation-of-nkg2d-ligands-by-nef-protein-from-elite-controllers-sensitizes-hiv-1-infected-cells-to-adcc
#6
Nirmin Alsahafi, Jonathan Richard, Jérémie Prévost, Mathieu Coutu, Nathalie Brassard, Matthew S Parsons, Daniel E Kaufmann, Mark Brockman, Andrés Finzi
HIV-1 Nef clones isolated from a rare subset of HIV-1-infected elite controllers (EC), with the ability to suppress viral load to undetectable levels in the absence of antiretroviral therapy, are unable to fully downregulate CD4 from the plasma membrane of CD4+ T cells. Residual CD4 left at the plasma membrane allows Env-CD4 interaction, which leads to increased exposure of Env CD4-induced epitopes and increases susceptibility of infected cells to antibody-dependent cellular cytotoxicity (ADCC). ADCC is mediated largely by natural killer (NK) cells, which control their activation status through the cumulative signals received through activating and inhibitory receptors...
June 14, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28605635/expression-of-herv-k108-envelope-interferes-with-hiv-1-production
#7
Sandra N Terry, Lara Manganaro, Alvaro Cuesta-Dominguez, Daria Brinzevich, Viviana Simon, Lubbertus C F Mulder
The human endogenous retroviruses (HERV)-K of the HML-2 group include full-length or near full-length elements encoding functional proteins, and are classified as type-1 or type-2 (type-1 has a deletion in the 5' end of the env gene). Because proteins of different retroviruses can interact, we hypothesized that HERV-K envelope (Env) could influence HIV-1 replication. Here we describe the negative effect of envelope expression of certain type-2 HERV-Ks on HIV-1 production. All HIV-1 and SIV strains tested were susceptible to various degrees to inhibition by the HERV-K108 envelope...
June 9, 2017: Virology
https://www.readbyqxmd.com/read/28580942/adenovirus-prime-env-protein-boost-vaccine-protects-against-neutralization-resistant-sivsme660-variants-in-rhesus-monkeys
#8
Brandon F Keele, Wenjun Li, Erica N Borducchi, Joseph P Nkolola, Peter Abbink, Bing Chen, Michael S Seaman, Dan H Barouch
Previous studies have shown that DNA prime, Ad5 boost vaccines protect against neutralization-sensitive but not neutralization-resistant virus variants within the SIVsmE660 swarm. Here we show that Ad prime, Env protein boost vaccines protect against neutralization-resistant SIVsmE660 variants. We perform two studies in rhesus monkeys with Ad35/Ad26 vectors expressing SIVmac239 Gag/Pol/Env with or without an AS01B-adjuvanted SIVmac32H gp140 protein boost. In a repetitive, low-dose challenge study, we observe robust protection against acquisition of infection by both Ad Alone and Ad/Env vaccines...
June 5, 2017: Nature Communications
https://www.readbyqxmd.com/read/28574482/immunologic-and-virologic-mechanisms-for-partial-protection-from-intravenous-challenge-by-an-integration-defective-siv-vaccine
#9
Chu Wang, Chunlai Jiang, Nan Gao, Kaikai Zhang, Donglai Liu, Wei Wang, Zhe Cong, Chuan Qin, Vitaly V Ganusov, Guido Ferrari, Celia LaBranche, David C Montefiori, Wei Kong, Xianghui Yu, Feng Gao
The suppression of viral loads and identification of selection signatures in non-human primates after challenge are indicators for effective human immunodeficiency virus (HIV)/simian immunodeficiency virus (SIV) vaccines. To mimic the protective immunity elicited by attenuated SIV vaccines, we developed an integration-defective SIV (idSIV) vaccine by inactivating integrase, mutating sequence motifs critical for integration, and inserting the cytomegalovirus (CMV) promoter for more efficient expression in the SIVmac239 genome...
June 2, 2017: Viruses
https://www.readbyqxmd.com/read/28539451/reducing-v3-antigenicity-and-immunogenicity-on-soluble-native-like-hiv-1-env-sosip-trimers
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
Ujjwal Rathore, Piyali Saha, Sannula Kesavardhana, Aditya Arun Kumar, Rohini Datta, Sivasankar Devanarayanan, Raksha Das, John R Mascola, Raghavan Varadarajan
The gp120 subunit of the HIV-1 envelope (Env) protein is heavily glycosylated at ∼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 alanines...
June 16, 2017: Journal of Biological Chemistry
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