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Viral glycoprotein-D

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https://www.readbyqxmd.com/read/28714909/the-interplay-between-the-host-receptor-and-influenza-virus-hemagglutinin-and-neuraminidase
#1
REVIEW
Lauren Byrd-Leotis, Richard D Cummings, David A Steinhauer
The hemagglutinin (HA) and neuraminidase (NA) glycoproteins of influenza A virus are responsible for the surface interactions of the virion with the host. Entry of the virus is mediated by functions of the HA: binding to cellular receptors and facilitating fusion of the virion membrane with the endosomal membrane. The HA structure contains receptor binding sites in the globular membrane distal head domains of the trimer, and the fusion machinery resides in the stem region. These sites have specific characteristics associated with subtype and host, and the differences often define species barriers...
July 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28650722/optimized-dna-vaccine-enhanced-by-adjuvant-il28b-induces-protective-immune-responses-against-herpes-simplex-virus-type-2-in-mice
#2
Yan Zhou, Ziyan Wang, Yongqing Xu, Zeqiang Zhang, Rui Hua, Wei Liu, Chunlai Jiang, Yan Chen, Wenying Yang, Wei Kong
Antigen-specific immune responses determine the efficacy of herpes simplex virus type 2 (HSV-2) vaccines. To optimize the immunogenicity of the antigen gD2, we developed the gD2ΔUL25 DNA vaccine encoding HSV-2 glycoprotein D and UL25 gene encoding viral capsid vertex proteins in this study. The gD2 and gD2ΔUL25 DNA vaccines were compared with formalin-inactivated HSV-2 (FI-HSV-2), and results showed a greater protective immune response induced by gD2ΔUL25 than by gD2. Therefore, gD2ΔUL25 was chosen to evaluate further using the IL28B adjuvant...
June 26, 2017: Viral Immunology
https://www.readbyqxmd.com/read/28631601/viral-genes-and-cellular-markers-associated-with-neurological-complications-during-herpesvirus-infections
#3
Carine L Holz, Rahul K Nelli, M Eilidh Wilson, Lila M Zarski, Walid Azab, Rachel Baumgardner, Nikolaus Osterrieder, Anthony Pease, Liangliang Zhang, Sarah Hession, Lutz S Goehring, Stephen B Hussey, Gisela Soboll Hussey
Despite the importance of neurological disorders associated with herpesviruses, the mechanism by which these viruses influence the central nervous system (CNS) has not been definitively established. Owing to the limitations of studying neuropathogenicity of human herpesviruses in their natural host, many aspects of their pathogenicity and immune response are studied in animal models. Here, we present an important model system that enables studying neuropathogenicity of herpesviruses in the natural host. Equine herpesvirus type 1 (EHV-1) is an alphaherpesvirus that causes a devastating neurological disease (EHV-1 myeloencephalopathy; EHM) in horses...
June 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28628828/sensitivity-to-bst-2-restriction-correlates-with-orthobunyavirus-host-range
#4
Mariana Varela, Ilaria M Piras, Catrina Mullan, Xiaohong Shi, Natasha L Tilston-Lunel, Rute Maria Pinto, Aislynn Taggart, Stephen R Welch, Stuart J D Neil, Felix Kreher, Richard M Elliott, Massimo Palmarini
Orthobunyaviruses include several recently emerging viruses of significant medical and veterinary importance. There is currently very limited understanding on what determines the host species range of these pathogens. In this study we discovered that BST-2/tetherin restricts orthobunyavirus replication in a host-specific manner. We show that viruses with human tropism (Oropouche virus and La Crosse virus) are restricted by sheep BST-2 but not by the human orthologue, while viruses with ruminant tropism (Schmallenberg virus and others) are restricted by human BST-2 but not by the sheep orthologue...
June 16, 2017: Virology
https://www.readbyqxmd.com/read/28604661/computational-design-of-trimeric-influenza-neutralizing-proteins-targeting-the-hemagglutinin-receptor-binding-site
#5
Eva-Maria Strauch, Steffen M Bernard, David La, Alan J Bohn, Peter S Lee, Caitlin E Anderson, Travis Nieusma, Carly A Holstein, Natalie K Garcia, Kathryn A Hooper, Rashmi Ravichandran, Jorgen W Nelson, William Sheffler, Jesse D Bloom, Kelly K Lee, Andrew B Ward, Paul Yager, Deborah H Fuller, Ian A Wilson, David Baker
Many viral surface glycoproteins and cell surface receptors are homo-oligomers, and thus can potentially be targeted by geometrically matched homo-oligomers that engage all subunits simultaneously to attain high avidity and/or lock subunits together. The adaptive immune system cannot generally employ this strategy since the individual antibody binding sites are not arranged with appropriate geometry to simultaneously engage multiple sites in a single target homo-oligomer. We describe a general strategy for the computational design of homo-oligomeric protein assemblies with binding functionality precisely matched to homo-oligomeric target sites...
July 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28544850/pcpp-adjuvanted-respiratory-syncytial-virus-rsv-sf-subunit-vaccine-self-assembled-supramolecular-complexes-enable-enhanced-immunogenicity-and-protection
#6
Corinne Cayatte, Alexander Marin, Gaurav Manohar Rajani, Kirsten Schneider-Ohrum, Angie Snell Bennett, Jason D Marshall, Alexander K Andrianov
PCPP, a well-defined polyphosphazene macromolecule, has been studied as an immunoadjuvant for a soluble form of the postfusion glycoprotein of respiratory syncytial virus (RSV sF), which is an attractive vaccine candidate for inducing RSV-specific immunity in mice and humans. We demonstrate that RSV sF-PCPP formulations induce high neutralization titers to RSV comparable to alum formulations even at a low PCPP dose and protect animals against viral challenge both in the lung and in the upper respiratory tract...
June 7, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28542541/varicella-zoster-virus-glycoprotein-c-increases-chemokine-mediated-leukocyte-migration
#7
Víctor González-Motos, Carina Jürgens, Birgit Ritter, Kai A Kropp, Verónica Durán, Olav Larsen, Anne Binz, Werner J D Ouwendijk, Tihana Lenac Rovis, Stipan Jonjic, Georges M G M Verjans, Beate Sodeik, Thomas Krey, Rudolf Bauerfeind, Thomas F Schulz, Benedikt B Kaufer, Ulrich Kalinke, Amanda E I Proudfoot, Mette M Rosenkilde, Abel Viejo-Borbolla
Varicella zoster virus (VZV) is a highly prevalent human pathogen that establishes latency in neurons of the peripheral nervous system. Primary infection causes varicella whereas reactivation results in zoster, which is often followed by chronic pain in adults. Following infection of epithelial cells in the respiratory tract, VZV spreads within the host by hijacking leukocytes, including T cells, in the tonsils and other regional lymph nodes, and modifying their activity. In spite of its importance in pathogenesis, the mechanism of dissemination remains poorly understood...
May 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28542478/structural-basis-of-nectin-1-recognition-by-pseudorabies-virus-glycoprotein-d
#8
An Li, Guangwen Lu, Jianxun Qi, Lili Wu, Kegong Tian, Tingrong Luo, Yi Shi, Jinghua Yan, George F Gao
An early and yet indispensable step in the alphaherpesvirus infection is the engagement of host receptors by the viral envelope glycoprotein D (gD). Of the thus-far identified gD receptors, nectin-1 is likely the most effective in terms of its wide usage by multiple alphaherpesviruses for cell entry. The molecular basis of nectin-1 recognition by the gD protein is therefore an interesting scientific question in the alphaherpesvirus field. Previous studies focused on the herpes simplex virus (HSV) of the Simplexvirus genus, for which both the free gD structure and the gD/nectin-1 complex structure were reported at high resolutions...
May 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28525755/antibodies-from-a-human-survivor-define-sites-of-vulnerability-for-broad-protection-against-ebolaviruses
#9
Anna Z Wec, Andrew S Herbert, Charles D Murin, Elisabeth K Nyakatura, Dafna M Abelson, J Maximilian Fels, Shihua He, Rebekah M James, Marc-Antoine de La Vega, Wenjun Zhu, Russell R Bakken, Eileen Goodwin, Hannah L Turner, Rohit K Jangra, Larry Zeitlin, Xiangguo Qiu, Jonathan R Lai, Laura M Walker, Andrew B Ward, John M Dye, Kartik Chandran, Zachary A Bornholdt
Experimental monoclonal antibody (mAb) therapies have shown promise for treatment of lethal Ebola virus (EBOV) infections, but their species-specific recognition of the viral glycoprotein (GP) has limited their use against other divergent ebolaviruses associated with human disease. Here, we mined the human immune response to natural EBOV infection and identified mAbs with exceptionally potent pan-ebolavirus neutralizing activity and protective efficacy against three virulent ebolaviruses. These mAbs recognize an inter-protomer epitope in the GP fusion loop, a critical and conserved element of the viral membrane fusion machinery, and neutralize viral entry by targeting a proteolytically primed, fusion-competent GP intermediate (GPCL) generated in host cell endosomes...
May 18, 2017: Cell
https://www.readbyqxmd.com/read/28520963/humoral-and-innate-antiviral-immunity-as-tools-to-clear-persistent-hiv-infection
#10
REVIEW
Guido Ferrari, Justin Pollara, Georgia D Tomaras, Barton F Haynes
Human immunodeficiency virus (HIV) type 1 uses the CD4 molecule as its principal receptor to infect T cells. HIV-1 integrates its viral genome into the host cell, leading to persistent infection wherein HIV-1 can remain transcriptionally silent in latently infected CD4+ T cells. On reactivation of replication-competent provirus, HIV-1 envelope glycoproteins (Env) are expressed and accumulate on the cell surface, allowing infected cells to be detected and targeted by endogenous immune responses or immune interventions...
March 15, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28404844/intramuscular-immunization-of-mice-with-the-live-attenuated-herpes-simplex-virus-1-vaccine-strain-vc2-expressing-equine-herpesvirus-1-ehv-1-glycoprotein-d-generates-anti-ehv-1-immune-responses-in-mice
#11
Shiliang A Liu, Brent A Stanfield, Vladimir N Chouljenko, Shan Naidu, Ingeborg Langohr, Fabio Del Piero, Jacqueline Ferracone, Alma A Roy, Konstantin G Kousoulas
Vaccination remains the best option to combat equine herpesvirus 1 (EHV-1) infection, and several different strategies of vaccination have been investigated and developed over the past few decades. Herein, we report that the live-attenuated herpes simplex virus 1 (HSV-1) VC2 vaccine strain, which has been shown to be unable to enter into neurons and establish latency in mice, can be utilized as a vector for the heterologous expression of EHV-1 glycoprotein D (gD) and that the intramuscular immunization of mice results in strong antiviral humoral and cellular immune responses...
June 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28396205/entry-inhibition-of-hsv-1-and-2-protects-mice-from-viral-lethal-challenge
#12
Nicola Clementi, Elena Criscuolo, Francesca Cappelletti, Paola Quaranta, Mauro Pistello, Roberta A Diotti, Giuseppe A Sautto, Alexander W Tarr, Federico Mailland, Daniela Concas, Roberto Burioni, Massimo Clementi, Nicasio Mancini
The present study focused on inhibition of HSV-1 and -2 replication and pathogenesis in vitro and in vivo, through the selective targeting of the envelope glycoprotein D. Firstly, a human monoclonal antibody (Hu-mAb#33) was identified that could neutralise both HSV-1 and -2 at nM concentrations, including clinical isolates from patients affected by different clinical manifestations and featuring different susceptibility to acyclovir in vitro. Secondly, the potency of inhibition of both infection by cell-free viruses and cell-to-cell virus transmission was also assessed...
April 8, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28381567/cbl-e3-ligase-mediates-the-removal-of-nectin-1-from-the-surface-of-herpes-simplex-virus-1-infected-cells
#13
Thibaut Deschamps, Christos Dogrammatzis, Ranajoy Mullick, Maria Kalamvoki
The Cbl E3 ligase has been linked to the down-modulation of surface signaling responses by inducing internalization of surface receptors. The adaptor protein CIN85 is a partner of Cbl that augments many of these interactions. Previously, an interaction was demonstrated between ICP0 and CIN85, which results in the removal of epidermal growth factor receptor (EGFR) from the surface of the infected cells with a concomitant attenuation of EGFR signaling. Here, we examined whether Cbl mediates the removal of the herpes simplex virus 1 (HSV-1) entry receptor Nectin-1 from the surface of infected cells...
June 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28378925/evaluation-of-recombinant-adenovirus-vaccines-based-on-glycoprotein-d-and-truncated-ul25-against-herpes-simplex-virus-type-2-in-mice
#14
Wei Liu, Yan Zhou, Ziyan Wang, Zeqiang Zhang, Qizhi Wang, Weiheng Su, Yan Chen, Yan Zhang, Feng Gao, Chunlai Jiang, Wei Kong
The high prevalence of herpes simplex virus 2 (HSV-2) infections in humans necessitates the development of a safe and effective vaccine that will need to induce vigorous T-cell responses to control the viral infection and transmission. We designed rAd-gD2rAd-gD2▵UL25rAd-▵UL25 to investigate whether recombinant replication-defective adenoviruses vaccine could induce specific T cell responses and protect mice against intravaginal HSV-2 challenge compared with FI-HSV-2. The recombinant adenovirus-based HSV-2 showed higher reductions in mortality and stronger antigen-specific T cell responses compared with FI-HSV-2 and the severity of genital lesions in the mice immunized with rAd-gD2▵UL25 was significantly decreased via eliciting IFN-γ-secreting T responses compared with rAd-gD2 and rAd-▵UL25 group in present study...
April 5, 2017: Microbiology and Immunology
https://www.readbyqxmd.com/read/28326469/hsv-1-interaction-to-3-o-sulfated-heparan-sulfate-in-mouse-derived-drg-explant-and-profiles-of-inflammatory-markers-during-virus-infection
#15
Harsh Sharthiya, Chanmoly Seng, T H Van Kuppevelt, Vaibhav Tiwari, Michele Fornaro
The molecular mechanism of herpes simplex virus (HSV) entry and the associated inflammatory response in the nervous system remain poorly understood. Using mouse-derived ex vivo dorsal root ganglia (DRG) explant model and single cell neurons (SCNs), in this study, we provided a visual evidence for the expression of heparan sulfate (HS) and 3-O-sulfated heparan sulfate (3-OS HS) followed by their interactions with HSV-1 glycoprotein B (gB) and glycoprotein D (gD) during cell entry. Upon heparanase treatment of DRG-derived SCN, a significant inhibition of HSV-1 entry was observed suggesting the involvement of HS role during viral entry...
June 2017: Journal of Neurovirology
https://www.readbyqxmd.com/read/28320973/structure-of-the-infectious-salmon-anemia-virus-receptor-complex-illustrates-a-unique-binding-strategy-for-attachment
#16
Jonathan D Cook, Azmiri Sultana, Jeffrey E Lee
Orthomyxoviruses are an important family of RNA viruses, which include the various influenza viruses. Despite global efforts to eradicate orthomyxoviral pathogens, these infections remain pervasive. One such orthomyxovirus, infectious salmon anemia virus (ISAV), spreads easily throughout farmed and wild salmonids, constituting a significant economic burden. ISAV entry requires the interplay of the virion-attached hemagglutinin-esterase and fusion glycoproteins. Preventing infections will rely on improved understanding of ISAV entry...
April 4, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28316015/expression-and-characterization-of-codon-optimized-crimean-congo-hemorrhagic-fever-virus-gn-glycoprotein-in-insect-cells
#17
Mehdi Rahpeyma, Alireza Samarbaf-Zadeh, Manoochehr Makvandi, Ata A Ghadiri, Stuart D Dowall, Fatemeh Fotouhi
Crimean-Congo hemorrhagic fever virus (CCHFV) is a major cause of tick-borne viral hemorrhagic disease in the world. Despite of its importance as a deadly pathogen, there is currently no licensed vaccine against CCHF disease. The attachment glycoprotein of CCHFV (Gn) is a potentially important target for protective antiviral immune responses. To characterize the expression of recombinant CCHFV Gn in an insect-cell-based system, we developed a gene expression system expressing the full-length coding sequence under a polyhedron promoter in Sf9 cells using recombinant baculovirus...
July 2017: Archives of Virology
https://www.readbyqxmd.com/read/28261207/investigating-substitutions-in-antibody-antigen-complexes-using-molecular-dynamics-a-case-study-with-broad-spectrum-influenza-a-antibodies
#18
William D Lees, Lenka Stejskal, David S Moss, Adrian J Shepherd
In studying the binding of host antibodies to the surface antigens of pathogens, the structural and functional characterization of antibody-antigen complexes by X-ray crystallography and binding assay is important. However, the characterization requires experiments that are typically time consuming and expensive: thus, many antibody-antigen complexes are under-characterized. For vaccine development and disease surveillance, it is often vital to assess the impact of amino acid substitutions on antibody binding...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28250127/attenuated-human-parainfluenza-virus-type-1-expressing-ebola-virus-glycoprotein-gp-administered-intranasally-is-immunogenic-in-african-green-monkeys
#19
Matthias Lingemann, Xueqiao Liu, Sonja Surman, Bo Liang, Richard Herbert, Ashley D Hackenberg, Ursula J Buchholz, Peter L Collins, Shirin Munir
The recent 2014-2016 Ebola virus (EBOV) outbreak prompted increased efforts to develop vaccines against EBOV disease. We describe the development and preclinical evaluation of an attenuated recombinant human parainfluenza virus type 1 (rHPIV1) expressing the membrane-anchored form of EBOV glycoprotein GP, as an intranasal (i.n.) EBOV vaccine. GP was codon optimized and expressed either as a full-length protein or as an engineered chimeric form in which its transmembrane and cytoplasmic tail (TMCT) domains were replaced with those of the HPIV1 F protein in an effort to enhance packaging into the vector particle and immunogenicity...
May 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28237822/shrnas-targeting-either-the-glycoprotein-or-polymerase-genes-inhibit-viral-haemorrhagic-septicaemia-virus-replication-in-zebrafish-zf4-cells
#20
Brian D Clarke, Kenneth A McColl, Alister C Ward, Timothy J Doran
Viral haemorrhagic septicaemia virus (VHSV) represents an important disease of finfish. To explore the potential of shRNAs to combat this disease nucleotide sequences of either the VHSV glycoprotein (G) or polymerase (L) gene were targeted. To test their function, shRNAs were expressed in zebrafish epithelial ZF-4 cells utilizing the zebrafish U6-2 promoter. Five of the six shRNA molecules successfully reduced VHSV replication by between 2 and 4 logs in titre relative to an irrelevant control shRNA at all MOIs and also reduced viral CPE at the highest MOI...
February 24, 2017: Antiviral Research
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