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Env protein

Jonathan Richard, Jérémie Prévost, Amy E Baxter, Benjamin von Bredow, Shilei Ding, Halima Medjahed, Gloria G Delgado, Nathalie Brassard, Christina M Stürzel, Frank Kirchhoff, Beatrice H Hahn, Matthew S Parsons, Daniel E Kaufmann, David T Evans, Andrés Finzi
The conformation of the HIV-1 envelope glycoprotein (Env) substantially impacts antibody recognition and antibody-dependent cellular cytotoxicity (ADCC) responses. In the absence of the CD4 receptor at the cell surface, primary Envs sample a "closed" conformation that occludes CD4-induced (CD4i) epitopes. The virus controls CD4 expression through the actions of Nef and Vpu accessory proteins, thus protecting infected cells from ADCC responses. However, gp120 shed from infected cells can bind to CD4 present on uninfected bystander cells, sensitizing them to ADCC mediated by CD4i antibodies (Abs)...
March 20, 2018: MBio
Patrick Küry, Avindra Nath, Alain Créange, Antonina Dolei, Patrice Marche, Julian Gold, Gavin Giovannoni, Hans-Peter Hartung, Hervé Perron
The causes of multiple sclerosis and amyotrophic lateral sclerosis have long remained elusive. A new category of pathogenic components, normally dormant within human genomes, has been identified: human endogenous retroviruses (HERVs). These represent ∼8% of the human genome, and environmental factors have reproducibly been shown to trigger their expression. The resulting production of envelope (Env) proteins from HERV-W and HERV-K appears to engage pathophysiological pathways leading to the pathognomonic features of MS and ALS, respectively...
March 15, 2018: Trends in Molecular Medicine
Eric Barklis, August O Staubus, Andrew Mack, Logan Harper, Robin Lid Barklis, Ayna Alfadhli
The matrix (MA) domain of the HIV-1 precursor Gag protein (PrGag) has been shown interact with the HIV-1 envelope (Env) protein, and to direct PrGag proteins to plasma membrane (PM) assembly sites by virtue of its affinity to phosphatidylinositol-4,5-bisphosphate (PI[4,5]P2). Unexpectedly, HIV-1 viruses with large MA deletions (ΔMA) have been shown to be conditionally infectious as long as they are matched with Env truncation mutant proteins or alternative viral glycoproteins. To characterize the interactions of wild type (WT) and ΔMA Gag proteins with PI(4,5)P2 and other acidic phospholipids, we have employed a set of lipid biosensors as probes...
March 14, 2018: Virology
Jackie Perrin, Aurélie Bary, Alexandre Vernay, Pierre Cosson
BACKGROUND: The envelope protein of lentiviruses are type I transmembrane proteins, and their transmembrane domain contains conserved potentially charged residues. This highly unusual feature would be expected to cause endoplasmic reticulum (ER) localization. The aim of this study was to determine by which means the HIV-1 Env protein is transported to the cell surface although its transmembrane domain contains a conserved arginine residue. RESULTS: We expressed various chimeric proteins and analyzed the influence of their transmembrane domain on their intracellular localization...
March 15, 2018: BMC Cell Biology
Monika Olech, Stephen Valas, Jacek Kuźmak
Small ruminant lentivirus (SRLV) infections are widespread in Poland and circulation of subtypes A1, A12, A13, B1 and B2 was detected. The present work aimed at extending previous study based on the analysis of a larger number of animals from single-species flocks. Animals were selected for genetic analysis based on serological reactivity towards a range of recombinant antigens derived from Gag and Env viral proteins. Phylogenetic analysis revealed the existence of subtypes B2 and A12 in both goats and sheep and subtypes A1 and B1 in goats only...
2018: PloS One
Jason Yolitz, Catherine Schwing, Julia Chang, Donald Van Ryk, Fatima Nawaz, Danlan Wei, Claudia Cicala, James Arthos, Anthony S Fauci
The HIV-1 envelope protein (Env) of early-replicating viruses encodes several distinct transmission signatures. One such signature involves a reduced number of potential N-linked glycosylation sites (PNGs). This transmission signature underscores the importance of posttranslational modifications in the fitness of early-replicating isolates. An additional signature in Env involves the overrepresentation of basic amino acid residues at a specific position in the Env signal peptide (SP). In this report, we investigated the potential impact of this SP signature on gp120 glycosylation and antigenicity...
February 20, 2018: Proceedings of the National Academy of Sciences of the United States of America
Devra D Huey, Brad Bolon, Krista M D La Perle, Priya Kannian, Steven Jacobson, Lee Ratner, Patrick L Green, Stefan Niewiesk
Chronic infection with human T-cell leukemia virus type 1 (HTLV1) can lead to adult T-cell leukemia (ATL). In contrast, infection with HTLV2 does not lead to leukemia, potentially because of distinct virus-host interactions and an active immune response that controls virus replication and, therefore, leukemia development. We created a humanized mouse model by injecting human umbilical-cord stem cells into the livers of immunodeficient neonatal NSG mice, resulting in the development of human lymphocytes that cannot mount an adaptive immune response...
February 1, 2018: Comparative Medicine
Ivelin S Georgiev, Michael Gordon Joyce, Rita E Chen, Kwanyee Leung, Krisha McKee, Aliaksandr Druz, Joseph G Van Galen, Masaru Kanekiyo, Yaroslav Tsybovsky, Eun Sung Yang, Yongping Yang, Priyamvada Acharya, Marie Pancera, Paul V Thomas, Timothy Wanninger, Hadi Yassine, Ulrich Baxa, Nicole Doria-Rose, Cheng Cheng, Barney S Graham, John R Mascola, Peter D Kwong
Antigen multimerization on a nanoparticle can result in improved neutralizing antibody responses. A platform that has been successfully used for displaying antigens from a number of different viruses is ferritin, a self-assembling protein nanoparticle that allows the attachment of multiple copies (twenty-four monomers or eight trimers) of a single antigen. Here we design two-component ferritin variants that allow the attachment of two diverse antigens on a single particle in a defined ratio and geometric pattern...
February 16, 2018: ACS Infectious Diseases
Tripti Shrivastava, Sweety Samal, Ashish K Tyagi, Sandeep Goswami, Naresh Kumar, Gabriel Ozorowski, Andrew B Ward, Bimal K Chakrabarti
Using HIV-1 envelope protein (Env)-based immunogens that closely mimic the conformation of functional HIV-1 Envs and represent the isolates prevalent in relevant geographical region is considered a rational approach towards developing HIV vaccine. We recently reported that like clade B Env, JRFL, membrane bound Indian clade C Env, 4-2.J41 is also efficiently cleaved and displays desirable antigenic properties for plasmid DNA immunization. Here, we evaluated the immune response in rabbit by injecting the animals with plasmid expressing membrane bound efficiently cleaved 4-2...
February 8, 2018: Vaccine
Anna-Janina Behrens, Abhinav Kumar, Max Medina-Ramirez, Albert Cupo, Kevin Marshall, Victor M Cruz Portillo, David J Harvey, Gabriel Ozorowski, Nicole Zitzmann, Ian A Wilson, Andrew B Ward, Weston B Struwe, John P Moore, Rogier W Sanders, Max Crispin
Broadly neutralizing antibodies (bNAbs) that target the trimeric HIV-1 envelope glycoprotein spike (Env) are tools that can guide the design of recombinant Env proteins intended to engage the predicted human germline precursors of bNAbs (gl-bNAbs). The protein components of gl-bNAb epitopes are often masked by glycans, while mature bNAbs can evolve to accommodate or bypass these shielding glycans. The design of germline-targeting Env immunogens therefore includes the targeted deletion of specific glycan sites...
February 8, 2018: Journal of Proteome Research
Massimiliano Bissa, Greta Forlani, Carlo Zanotto, Giovanna Tosi, Carlo De Giuli Morghen, Roberto S Accolla, Antonia Radaelli
A complete eradication of an HIV infection has never been achieved by vaccination and the search for new immunogens that can induce long-lasting protective responses is ongoing. Avipoxvirus recombinants are host-restricted for replication to avian species and they do not have the undesired side effects induced by vaccinia recombinants. In particular, Fowlpox (FP) recombinants can express transgenes over long periods and can induce protective immunity in mammals, mainly due to CD4-dependent CD8+ T cells. In this context, the class II transactivator (CIITA) has a pivotal role in triggering the adaptive immune response through induction of the expression of class-II major histocompatibility complex molecule (MHC-II), that can present antigens to CD4+ T helper cells...
2018: PloS One
Chitra Upadhyay, Roya Feyznezhad, Weiming Yang, Hui Zhang, Susan Zolla-Pazner, Catarina E Hioe
HIV-1 envelope glycoprotein (Env) mediates virus attachment and entry into the host cells. Like other membrane-bound and secreted proteins, HIV-1 Env contains at its N terminus a signal peptide (SP) that directs the nascent Env to the endoplasmic reticulum (ER) where Env synthesis and post-translational modifications take place. SP is cleaved during Env biosynthesis but potentially influences the phenotypic traits of the Env protein. The Env SP sequences of HIV-1 isolates display high sequence variability, and the significance of such variability is unclear...
January 25, 2018: PLoS Pathogens
Alba Torrents de la Peña, Steven W de Taeye, Kwinten Sliepen, Celia C LaBranche, Judith A Burger, Edith E Schermer, David C Montefiori, John P Moore, Per Johan Klasse, Rogier W Sanders
Recombinant soluble HIV-1 envelope glycoprotein (Env) SOSIP trimers are a design platform for inducing broadly neutralizing antibodies (bNAbs) by vaccination. To date, these and alternative designs of native-like trimers given singly or in pairs, have not induced bNAbs in test animals such as rabbits or macaques. Here, we have evaluated whether trivalent and tetravalent combinations of SOSIP trimers from clades A, B and C, delivered simultaneously or sequentially, induce better neutralizing antibody responses in rabbits than when given alone...
January 24, 2018: Journal of Virology
Sabine Johnson, Jun X Wheeler, Robin Thorpe, Mary Collins, Yasuhiro Takeuchi, Yuan Zhao
Lentiviral vectors (LVs) have been successfully used in clinical trials showing long term therapeutic benefits. Studying the role of cellular proteins in lentivirus HIV-1 life cycle can help understand virus assembly and budding, leading to improvement of LV production for gene therapy. Lentiviral vectors were purified using size exclusion chromatography (SEC). The cellular protein composition of LVs produced by two different methods was compared: the transient transfection system pseudotyped with the VSV-G envelope, currently used in clinical trials, and a stable producer cell system using a non-toxic envelope derived from cat endogenous retrovirus RD114, RDpro...
January 17, 2018: Biologicals: Journal of the International Association of Biological Standardization
Sayaka Sukegawa, Eri Miyagi, Fadila Bouamr, Helena Farkašová, Klaus Strebel
Human mannose receptor 1 (hMRC1) is expressed on the surface of most tissue macrophages, dendritic cells, and select lymphatic or liver endothelial cells. HMRC1 contributes to the binding of HIV-1 to monocyte-derived macrophages (MDMs) and is involved in the endocytic uptake of HIV-1 into these cells. Here, we identify hMRC1 as an antiviral factor that inhibits virus release through a bone marrow stromal antigen 2 (BST-2)-like mechanism. Virions produced in the presence of hMRC1 accumulated in clusters at the cell surface but were fully infectious...
January 16, 2018: Cell Reports
Bibek Parajuli, Kriti Acharya, Harry C Bach, Bijay Parajuli, Shiyu Zhang, Amos B Smith, Cameron F Abrams, Irwin Chaiken
We previously reported first generation recombinant DAVEI construct, a dual action virus entry inhibitor composed of cyanovirin-N (CVN) fused to a membrane proximal external region (MPER) or its derivative peptide Trp3. DAVEI exhibits potent and irreversible inactivation of HIV-1 viruses by dual engagement of gp120 and gp41. However, the promiscuity of CVN to associate with multiple glycosylation sites in gp120 and its multivalency limit current understanding of the molecular arrangement of the DAVEI molecules on trimeric spike...
January 17, 2018: Biochemical Journal
Raymond W Wong, Clifford A Lingwood, Mario A Ostrowski, Tyler Cabral, Alan Cochrane
The capacity of HIV-1 to develop resistance to current drugs calls for innovative strategies to control this infection. We aimed at developing novel inhibitors of HIV-1 replication by targeting viral RNA processing-a stage dependent on conserved host processes. We previously reported that digoxin is a potent inhibitor of this stage. Herein, we identify 12 other cardiac glycoside/aglycones or cardiotonic steroids (CSs) that impede HIV growth in HIV-infected T cells from clinical patients at IC50s (1.1-1.3 nM) that are 2-26 times below concentrations used in patients with heart conditions...
January 16, 2018: Scientific Reports
Youyi Fong, Xiaoying Shen, Vicki C Ashley, Aaron Deal, Kelly E Seaton, Chenchen Yu, Shannon P Grant, Guido Ferrari, Allan C deCamp, Robert T Bailer, Richard A Koup, David Montefiori, Barton F Haynes, Marcella Sarzotti-Kelsoe, Barney S Graham, Lindsay N Carpp, Scott M Hammer, Magda Sobieszczyk, Shelly Karuna, Edith Swann, Edwin DeJesus, Mark Mulligan, Ian Frank, Susan Buchbinder, Richard M Novak, M Juliana McElrath, Spyros Kalams, Michael Keefer, Nicole A Frahm, Holly E Janes, Peter B Gilbert, Georgia D Tomaras
Background: HVTN 505 was an HIV-1 preventive vaccine efficacy trial of a DNA/recombinant adenovirus serotype 5 (rAd5) vaccine regimen. We assessed antibody responses measured one month post-final vaccination (Month 7) as correlates of HIV-1 acquisition risk. Methods: Binding antibody responses were quantified in serum samples from 25 primary endpoint vaccine cases (diagnosed with HIV-1 infection between Month 7 and 24) and 125 randomly sampled frequency-matched vaccine controls (HIV-1 negative at Month 24)...
January 8, 2018: Journal of Infectious Diseases
Aneta Pluta, Lorraine M Albritton, Marzena Rola-Łuszczak, Jacek Kuźmak
BACKGROUND: Bovine leukemia virus (BLV) is a deltaretrovirus infecting bovine B cells and causing enzootic bovine leucosis. The SU or surface subunit, gp51, of its envelope glycoprotein is involved in receptor recognition and virion attachment. It contains the major neutralizing and CD4+ and CD8+ T cell epitopes found in naturally infected animals. In this study, we aimed to determine global variation and conservation within gp51 in the context of developing an effective global BLV vaccine...
January 8, 2018: Retrovirology
Tyler Milston Renner, Kasandra Bélanger, Cindy Lam, Maria Rosales Gerpe, Joanne Eileen McBane, Marc-André Langlois
The glycosylated Gag protein (gPr80) of murine leukemia viruses (MLVs) has been shown to exhibit multiple roles in facilitating retrovirus release, infection and resistance to host-encoded retroviral restriction factors such as APOBEC3, SERINC3 and SERINC5. One way gPr80 helps MLVs escape host innate immune restriction is by increasing capsid stability, a feature that protects viral replication intermediates from being detected by cytosolic DNA sensors. gPr80 also increases the resistance of MLVs against deamination and restriction by mouse APOBEC3 (mA3)...
January 3, 2018: Journal of Virology
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