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Viral glycoprotein-D

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https://www.readbyqxmd.com/read/29678950/mapping-interaction-sites-on-human-chemokine-receptors-by-deep-mutational-scanning
#1
Jeremiah D Heredia, Jihye Park, Riley J Brubaker, Steven K Szymanski, Kevin S Gill, Erik Procko
Chemokine receptors CXCR4 and CCR5 regulate WBC trafficking and are engaged by the HIV-1 envelope glycoprotein gp120 during infection. We combine a selection of human CXCR4 and CCR5 libraries comprising nearly all of ∼7000 single amino acid substitutions with deep sequencing to define sequence-activity landscapes for surface expression and ligand interactions. After consideration of sequence constraints for surface expression, known interaction sites with HIV-1-blocking Abs were appropriately identified as conserved residues following library sorting for Ab binding, validating the use of deep mutational scanning to map functional interaction sites in G protein-coupled receptors...
April 20, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29670605/antiviral-immunotoxin-against-bovine-herpesvirus-1-targeted-inhibition-of-viral-replication-and-apoptosis-of-infected-cell
#2
Jian Xu, Xiaoyang Li, Bo Jiang, Xiaoyu Feng, Jing Wu, Yunhong Cai, Xixi Zhang, Xiufen Huang, Joshua E Sealy, Munir Iqbal, Yongqing Li
Bovine herpesvirus 1 (BoHV-1) is a highly contagious viral pathogen which causes infectious bovine rhinotracheitis in cattle worldwide. Currently, there is no antiviral prophylactic treatment available capable of mitigating the disease impact and facilitating recovery from latent infection. In this study, we have engineered a novel recombinant anti-BoHV-1 immunotoxin construct termed "BoScFv-PE38" that consists of a single-chain monoclonal antibody fragment (scFv) fused with an active domain of Pseudomonas exotoxin A as a toxic effector (PE38)...
2018: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29669253/an-antibody-targeting-the-fusion-machinery-neutralizes-dual-tropic-infection-and-defines-a-site-of-vulnerability-on-epstein-barr-virus
#3
Joost Snijder, Michael S Ortego, Connor Weidle, Andrew B Stuart, Matthew D Gray, M Juliana McElrath, Marie Pancera, David Veesler, Andrew T McGuire
Epstein-Barr virus (EBV) is a causative agent of infectious mononucleosis and is associated with 200,000 new cases of cancer and 140,000 deaths annually. Subunit vaccines against this pathogen have focused on the gp350 glycoprotein and remain unsuccessful. We isolated human antibodies recognizing the EBV fusion machinery (gH/gL and gB) from rare memory B cells. One anti-gH/gL antibody, AMMO1, potently neutralized infection of B cells and epithelial cells, the two major cell types targeted by EBV. We determined a cryo-electron microscopy reconstruction of the gH/gL-gp42-AMMO1 complex and demonstrated that AMMO1 bound to a discontinuous epitope formed by both gH and gL at the Domain-I/Domain-II interface...
April 17, 2018: Immunity
https://www.readbyqxmd.com/read/29617845/a-small-molecule-cd4-mimetic-compound-protects-blt-humanized-mice-from-human-immunodeficiency-virus-infection
#4
Amy M Princiotto, Vladimir D Vrbanac, Bruno Melillo, Jongwoo Park, Andrew M Tager, Amos B Smith, Joseph Sodroski, Navid Madani
Background: Small-molecule CD4-mimetic compounds (CD4mc) inhibit human immunodeficiency virus (HIV-1) entry by blocking binding to the CD4 receptor and by premature triggering of the viral envelope glycoprotein (Env) spike. Methods: The efficacy of a CD4mc in protecting bone-marrow-liver-thymus (BLT) humanized mice from vaginal HIV-1 challenge was evaluated. Results: Intravaginal application of the CD4mc JP-III-48, either prior to or simultaneously with virus challenge, protected BLT humanized mice from HIV-1JR-CSF infection in a dose-dependent manner...
March 29, 2018: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29593038/conformational-stability-of-the-hemagglutinin-of-h5n1-influenza-a-viruses-influences-susceptibility-to-broadly-neutralizing-stem-antibodies
#5
Wei Wang, Hyo Sook Song, Paul W Keller, Esmeralda Alvarado-Facundo, Russell Vassell, Carol D Weiss
Vaccines that elicit broadly neutralizing antibodies to the conserved stem of hemagglutinin (HA) are being developed as universal influenza vaccines that protect against influenza across multiple years. However, different influenza strains, even those in the same subtype with identical stem sequences, can vary in susceptibility to broadly neutralizing stem antibodies, and the reasons are not understood. Here we studied potential mechanisms underlying different sensitivities of a panel of H5N1 HA-pseudoviruses to broadly neutralizing stem antibodies...
March 28, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29578688/unprecedented-role-of-hybrid-n-glycans-as-ligands-for-hiv-1-broadly-neutralizing-antibodies
#6
Vidya S Shivatare, Sachin S Shivatare, Chang-Chun David Lee, Chi-Hui Liang, Kuo-Shiang Liao, Yang-Yu Cheng, Gannerla Saidachary, Chung-Yi Wu, Nan-Horng Lin, Peter D Kwong, Dennis R Burton, Chung-Yi Wu, Chi-Huey Wong
The development of HIV vaccine has been hampered by the extraordinary mutability and genetic diversity of the virus, particularly the substantial sequence diversity of gp120 and gp 41 envelope glycoproteins existing in more than 2,000 HIV variants. The highly diverse glycans on HIV spikes are commonly considered as immunologically silent self-antigens; however, the discovery of highly potent broadly neutralizing antibodies (bNAbs) from HIV patients targeting the viral surface glycans has raised a major question about the origin of their antigens...
March 26, 2018: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/29563201/evaluation-of-fluorescence-microsphere-immunoassay-for-the-detection-of-antibodies-to-rift-valley-fever-nucleocapsid-protein-and-glycoproteins
#7
I K Ragan, A S Davis, D S McVey, J A Richt, R R Rowland, W C Wilson
Rift Valley Fever virus (RVFV) is a mosquito-borne zoonotic virus that infects ruminants including cattle, sheep, goats, camels and buffalo. Multiplexing diagnostic assays that can simultaneously detect antibodies against multiple RVFV antigens offer a high throughput test for disease surveillance and vaccine evaluations. We describe the improvement and evaluation of a previously developed fluorescence microsphere immunoassay (FMIA) for the detection of IgG and IgM antibodies against the RVFV glycoproteins (Gn) and the immunogenic nucleocapsid protein (Np)...
March 21, 2018: Journal of Clinical Microbiology
https://www.readbyqxmd.com/read/29561264/hiv-1-env-trimer-opens-through-an-asymmetric-intermediate-in-which-individual-protomers-adopt-distinct-conformations
#8
Xiaochu Ma, Maolin Lu, Jason Gorman, Daniel S Terry, Xinyu Hong, Zhou Zhou, Hong Zhao, Roger B Altman, James Arthos, Scott C Blanchard, Peter D Kwong, James B Munro, Walther Mothes
HIV-1 entry into cells requires binding of the viral envelope glycoprotein (Env) to receptor CD4 and coreceptor. Imaging of individual Env molecules on native virions shows Env trimers to be dynamic, spontaneously transitioning between three distinct well-populated conformational states: a pre-triggered Env (State 1), a default intermediate (State 2) and a three-CD4-bound conformation (State 3), which can be stabilized by binding of CD4 and coreceptor-surrogate antibody 17b. Here, using single-molecule Fluorescence Resonance Energy Transfer (smFRET), we show the default intermediate configuration to be asymmetric, with individual protomers adopting distinct conformations...
March 21, 2018: ELife
https://www.readbyqxmd.com/read/29540595/role-of-the-e2-hypervariable-region-hvr1-in-the-immunogenicity-of-a-recombinant-hcv-vaccine
#9
John L M Law, Michael Logan, Jason Wong, Juthika Kundu, Darren Hockman, Amir Landi, Chao Chen, Kevin Crawford, Mark Wininger, Janelle Johnson, Catalina Mesa Prince, Elzbieta Dudek, Ninad Mehta, D Lorne Tyrrell, Michael Houghton
Current evidence supports a protective role for virus neutralizing antibodies in immunity against HCV infection. Many cross-neutralizing monoclonal antibodies have been identified. These antibodies have been shown to protect or clear infection in animal models. Previous clinical trials have shown a gpE1/gpE2 vaccine can induce antibodies that neutralize the in vitro infectivity of all the major HCVcc genotypes around the world. However, cross-neutralization appeared to favour certain genotypes with significant but lower neutralization against others...
March 14, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29529215/heparan-sulfate-proteoglycans-serve-as-an-attachment-factor-for-rabies-virus-entry-and-infection
#10
Michihito Sasaki, Paulina D Anindita, Naoto Ito, Makoto Sugiyama, Michael Carr, Hideo Fukuhara, Toyoyuki Ose, Katsumi Maenaka, Ayato Takada, William W Hall, Yasuko Orba, Hirofumi Sawa
Rabies virus (RABV) is the causative agent of fatal neurological disease. Cellular attachment is the initial and essential step for viral infections. Although extensive studies have demonstrated that RABV utilizes various target cell molecules to mediate infection, no specific molecule has been identified as an attachment factor for RABV infection. Here we demonstrate that cellular heparan sulfate (HS) supports RABV adhesion and subsequent entry into target cells. Enzymatic removal of HS reduced the cellular susceptibility to RABV infection and heparin, a highly sulfated form of HS, blocked viral adhesion and infection...
February 26, 2018: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29528415/epitope-specific-humoral-responses-to-human-cytomegalovirus-glycoprotein-b-vaccine-with-mf59-anti-ad2-levels-correlate-with-protection-from-viremia
#11
Ilona Baraniak, Barbara Kropff, Gary R McLean, Sylvie Pichon, Fabienne Piras-Douce, Richard S B Milne, Colette Smith, Michael Mach, Paul D Griffiths, Matthew B Reeves
The human cytomegalovirus (HCMV) virion envelope protein glycoprotein B (gB) is essential for viral entry and represents a major target for humoral responses following infection. Previously, a phase-2 placebo-controlled clinical trial conducted in solid organ transplant candidates demonstrated that vaccination with gB plus MF59 adjuvant significantly increased gB ELISA antibody levels whose titer correlated directly with protection against post-transplant viremia. The aim of the current study was to investigate in more detail this protective humoral response in vaccinated seropositive transplant recipients...
March 8, 2018: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29514901/importance-of-neutralizing-monoclonal-antibodies-targeting-multiple-antigenic-sites-on-mers-cov-spike-to-avoid-neutralization-escape
#12
Lingshu Wang, Wei Shi, James D Chappell, M Gordon Joyce, Yi Zhang, Masaru Kanekiyo, Michelle M Becker, Neeltje van Doremalen, Robert Fischer, Nianshuang Wang, Kizzmekia S Corbett, Misook Choe, Rosemarie D Mason, Joseph G Van Galen, Tongqing Zhou, Kevin O Saunders, Kathleen M Tatti, Lia M Haynes, Peter D Kwong, Kayvon Modjarrad, Wing-Pui Kong, Jason S McLellan, Mark R Denison, Vincent J Munster, John R Mascola, Barney S Graham
Middle East Respiratory Syndrome coronavirus (MERS-CoV) causes a highly lethal pulmonary infection with ∼35% mortality. The potential for a future pandemic originating from animal reservoirs or healthcare-associated events is a major public health concern. There are no vaccines or therapeutic agents currently available for MERS-CoV. Using a probe-based single B cell-cloning strategy, we have identified and characterized multiple neutralizing mAbs specifically binding to the receptor binding domain (RBD) or S1 (non-RBD) regions from a convalescent MERS-CoV-infected patient and from immunized rhesus macaques...
March 7, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29496992/distinct-functions-for-the-membrane-proximal-ectodomain-region-mper-of-hiv-1-gp41-in-cell-free-and-cell-cell-viral-transmission-and-cell-cell-fusion
#13
Vani G S Narasimhulu, Anna K Bellamy-McIntyre, Annamarie E Laumaea, Chan-Sien Lay, David N Harrison, Hannah A D King, Heidi E Drummer, Pantelis Poumbourios
HIV-1 is spread by cell-free virions and by cell-cell viral transfer. We asked whether the structure and function of a broad neutralizing antibody (bNAb) epitope, the membrane-proximal ectodomain region (MPER) of the viral gp41 transmembrane glycoprotein, differ in cell-free and cell-cell transmitted viruses and whether this difference could be related to Ab neutralization sensitivity. Whereas cell-free viruses bearing W666A and I675A substitutions in the MPER lacked infectivity, cell-associated mutant viruses were able to initiate robust spreading infection...
March 1, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29455326/new-tetrameric-forms-of-the-rotavirus-nsp4-with-antiparallel-helices
#14
Sushant Kumar, Raghavendra Ramappa, Kiranmayee Pamidimukkala, C D Rao, K Suguna
Rotavirus nonstructural protein 4, the first viral enterotoxin to be identified, is a multidomain, multifunctional glycoprotein. Earlier, we reported a Ca2+ -bound coiled-coil tetrameric structure of the diarrhea-inducing region of NSP4 from the rotavirus strains SA11 and I321 and a Ca2+ -free pentameric structure from the rotavirus strain ST3, all with a parallel arrangement of α-helices. pH was found to determine the oligomeric state: a basic pH favoured a tetramer, whereas an acidic pH favoured a pentamer...
February 17, 2018: Archives of Virology
https://www.readbyqxmd.com/read/29392692/lentiviral-transduction-of-primary-human-glioblastoma-cultures
#15
Joshua D Frenster, Julio Inocencio, Dimitris G Placantonakis
This chapter provides detailed step-by-step instructions for the production of lentiviral particles and the transduction of primary human glioblastoma cultures. Lentiviruses stably transduce both dividing and non-dividing cells, such as quiescent cancer stem cell populations. The viral envelope is pseudotyped with the vesicular stomatitis virus envelope glycoprotein G (VSV-G), which renders the lentiviral particles pantropic, so that they can infect theoretically all cell types. The third generation packaging system used in this protocol produces lentiviruses with important safety features, including replication incompetence and self-inactivation (SIN)...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29386288/hiv-1-envelope-glycoproteins-from-diverse-clades-differentiate-antibody-responses-and-durability-among-vaccinees
#16
Nicole L Yates, Allan C deCamp, Bette T Korber, Hua-Xin Liao, Carmela Irene, Abraham Pinter, James Peacock, Linda J Harris, Sheetal Sawant, Peter Hraber, Xiaoying Shen, Supachai Rerks-Ngarm, Punnee Pitisuttithum, Sorachai Nitayapan, Phillip W Berman, Merlin L Robb, Giuseppe Pantaleo, Susan Zolla-Pazner, Barton F Haynes, S Munir Alam, David C Montefiori, Georgia D Tomaras
Induction of broadly cross-reactive anti-viral humoral responses with the capacity to target globally diverse circulating strains is a key goal for HIV-1 immunogen design. A major gap in the field is the identification of diverse HIV-1 envelope antigens to evaluate vaccine regimens for binding antibody breadth. In this study, we define unique antigen panels to map HIV-1 vaccine-elicited antibody breadth and durability. Diverse HIV-1 envelope glycoproteins were selected based on genetic and geographic diversity to cover the global epidemic, with a focus on sexually acquired transmitted/founder viruses with a tier-2 neutralization phenotype...
January 31, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29353147/prediction-of-conserved-sites-and-domains-in-glycoproteins-b-c-and-d-of-herpes-viruses
#17
Muhammad Asif Rasheed, Abdur Rahman Ansari, Awais Ihsan, Muhammad Tariq Navid, Shahid Ur-Rehman, Sohail Raza
Glycoprotein B (gB), C (gC) and D (gD) of herpes simplex virus are implicated in virus adsorption and penetration. The gB, gC and gD are glycoproteins for different processes of virus binding and attachment to the host cells. Moreover, their expression is necessary and sufficient to induce cell fusion in the absence of other glycoproteins. Egress of herpes simplex virus (HSV) and other herpes viruses from cells involves extensive modification of cellular membranes and sequential envelopment, de-envelopment and re-envelopment steps...
March 2018: Microbial Pathogenesis
https://www.readbyqxmd.com/read/29346393/computational-study-of-hiv-gp120-as-a-target-for-polyanionic-entry-inhibitors-exploiting-the-v3-loop-region
#18
Louis R Hollingsworth, Anne M Brown, Richard D Gandour, David R Bevan
Multiple approaches are being utilized to develop therapeutics to treat HIV infection. One approach is designed to inhibit entry of HIV into host cells, with a target being the viral envelope glycoprotein, gp120. Polyanionic compounds have been shown to be effective in inhibiting HIV entry, with a mechanism involving electrostatic interactions with the V3 loop of gp120 being proposed. In this study, we applied computational methods to elucidate molecular interactions between the repeat unit of the precisely alternating polyanion, Poly(4,4'-stilbenedicarboxylate-alt-maleic acid) (DCSti-alt-MA) and the V3 loop of gp120 from strains of HIV against which these polyanions were previously tested (IIIb, BaL, 92UG037, JR-CSF) as well as two strains for which gp120 crystal structures are available (YU2, 2B4C)...
2018: PloS One
https://www.readbyqxmd.com/read/29340221/recombinant-antibodies-to-the-ebola-virus-glycoprotein
#19
A A Panina, I G Dementieva, T K Aliev, V A Toporova, D S Balabashin, M N Bokov, L P Pozdnyakova, O B Shchemchukova, D A Dolgikh, P G Sveshnikov, M P Kirpichnikov
Currently, there are no approved therapies for targeted prevention and treatment of Ebola hemorrhagic fever. In the present work, we describe the development of a eukaryotic expression system for the production of three full-length chimeric antibodies (IgG1-kappa isotypes) GPE118, GPE325, and GPE534 to the recombinant glycoprotein of the Ebola virus (EBOV GP), which is a key factor in the pathogenicity of the disease. The immunochemical properties of the obtained antibodies were studied by immunoblotting and indirect, direct, and competitive ELISA using the recombinant EBOV proteins rGPdTM, NP, and VP40...
October 2017: Acta Naturae
https://www.readbyqxmd.com/read/29321320/hiv-1-specific-iga-monoclonal-antibodies-from-an-hiv-1-vaccinee-mediate-galactosylceramide-blocking-and-phagocytosis
#20
Saintedym Wills, Kwan-Ki Hwang, Pinghuang Liu, S Moses Dennison, Matthew Zirui Tay, Xiaoying Shen, Justin Pollara, Judith T Lucas, Robert Parks, Supachai Rerks-Ngarm, Punnee Pitisuttithum, Sorachai Nitayapan, Jaranit Kaewkungwal, Rasmi Thomas, Jerome H Kim, Nelson L Michael, Merlin L Robb, Mike McRaven, David C Montefiori, Thomas J Hope, Hua-Xin Liao, M Anthony Moody, Guido Ferrari, Barton F Haynes, S Munir Alam, Mattia Bonsignori, Georgia D Tomaras
Vaccine-elicited humoral immune responses comprise an array of antibody forms and specificities, with only a fraction contributing to protective host immunity. Elucidation of antibody effector functions responsible for protective immunity against human immunodeficiency virus type 1 (HIV-1) acquisition is a major goal for the HIV-1 vaccine field. Immunoglobulin A (IgA) is an important part of the host defense against pathogens; however, little is known about the role of vaccine-elicited IgA and its capacity to mediate antiviral functions...
April 1, 2018: Journal of Virology
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