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Viral glycoprotein-D

Jessica A Flynn, Eberhard Durr, Ryan Swoyer, Pedro J Cejas, Melanie S Horton, Jennifer D Galli, Scott A Cosmi, Amy S Espeseth, Andrew J Bett, Lan Zhang
Infection with Respiratory Syncytial Virus (RSV) causes both upper and lower respiratory tract disease in humans, leading to significant morbidity and mortality in both young children and older adults. Currently, there is no licensed vaccine available, and therapeutic options are limited. During the infection process, the type I viral fusion (F) glycoprotein on the surface of the RSV particle rearranges from a metastable prefusion conformation to a highly stable postfusion form. In people naturally infected with RSV, most potent neutralizing antibodies are directed to the prefusion form of the F protein...
2016: PloS One
T N Figueira, L M Palermo, A S Veiga, D Huey, C A Alabi, N C Santos, J C Welsch, C Mathieu, B Horvat, S Niewiesk, A Moscona, M A R B Castanho, M Porotto
: Measles virus (MV) infection is undergoing resurgence and remains one of the leading causes of death among young children worldwide despite the availability of an effective measles vaccine. MV infects its target cells by coordinated action of the MV hemagglutinin (H) and fusion (F) envelope glycoproteins; upon receptor engagement by H, the pre-fusion F undergoes a structural transition, extending and inserting into the target cell membrane and then re-folding into a post-fusion structure that fuses the viral and cell membranes...
October 12, 2016: Journal of Virology
Arjun K Bhargava, Paul W Rothlauf, Claude Krummenacher
Herpes simplex virus (HSV) uses the cell adhesion molecule nectin-1 as a receptor to enter neurons and epithelial cells. The viral glycoprotein D (gD) is used as a non-canonical ligand for nectin-1. The gD binding site on nectin-1 overlaps with a functional adhesive site involved in nectin-nectin homophilic trans-interaction. Consequently, when nectin-1 is engaged with a cellular ligand at cell junctions, the gD binding site is occupied. Here we report that HSV gD is able to disrupt intercellular homophilic trans-interaction of nectin-1 and induce a rapid redistribution of nectin-1 from cell junctions...
October 7, 2016: Virology
Yu Okubo, Hiroaki Uchida, Aika Wakata, Takuma Suzuki, Tomoko Shibata, Hitomi Ikeda, Miki Yamaguchi, Justus B Cohen, Joseph C Glorioso, Mitsuo Tagaya, Hirofumi Hamada, Hideaki Tahara
: Membrane fusion, which is the key process for both initial cell entry and subsequent lateral spread of herpes simplex virus (HSV), requires the four envelope glycoproteins gB, gD, gH, and gL. Syncytial mutations, predominantly mapped to the gB and gK genes, confer hyperfusogenicity on HSV and cause multinucleated giant cells, termed syncytia. Here, we asked whether interaction of gD with a cognate entry receptor remains indispensable for initiating membrane fusion of syncytial strains...
October 5, 2016: Journal of Virology
Nicolò Mauro, Paolo Ferruti, Elisabetta Ranucci, Amedea Manfredi, Angela Berzi, Mario Clerici, Valeria Cagno, David Lembo, Alessandro Palmioli, Sara Sattin
The initial steps of viral infections are mediated by interactions between viral proteins and cellular receptors. Blocking the latter with high-affinity ligands may inhibit infection. DC-SIGN, a C-type lectin receptor expressed by immature dendritic cells and macrophages, mediates human immunodeficiency virus (HIV) infection by recognizing mannose clusters on the HIV-1 gp120 envelope glycoprotein. Mannosylated glycodendrimers act as HIV entry inhibitors thanks to their ability to block this receptor. Previously, an amphoteric, but prevailingly cationic polyamidoamine named AGMA1 proved effective as infection inhibitor for several heparan sulfate proteoglycan-dependent viruses, such as human papilloma virus HPV-16 and herpes simplex virus HSV-2...
2016: Scientific Reports
Toshana L Foster, Harry Wilson, Shilpa S Iyer, Karen Coss, Katie Doores, Sarah Smith, Paul Kellam, Andrés Finzi, Persephone Borrow, Beatrice H Hahn, Stuart J D Neil
Interferon-induced transmembrane proteins (IFITMs) restrict the entry of diverse enveloped viruses through incompletely understood mechanisms. While IFITMs are reported to inhibit HIV-1, their in vivo relevance is unclear. We show that IFITM sensitivity of HIV-1 strains is determined by the co-receptor usage of the viral envelope glycoproteins as well as IFITM subcellular localization within the target cell. Importantly, we find that transmitted founder HIV-1, which establishes de novo infections, is uniquely resistant to the antiviral activity of IFITMs...
October 12, 2016: Cell Host & Microbe
Olga Leplina, Nataliya Starostina, Olga Zheltova, Alexandr Ostanin, Ekaterina Shevela, Elena Chernykh
Recurrent herpes simplex labialis caused predominantly with herpes simplexvirus 1(HSV-1) is a major problem, for which various treatments have minimal impact. Given the important role of the immune system in controlling virus infection, an activation of virus-specific immune responses, in particular,using dendritic cell (DCs) vaccines, seems to be a promising approach for the treatment of patients with frequent recurrences of herpes labialis. The current paper presents the results of a pilot study of the safety and efficacy of DC vaccines in 14 patients with recurrent HSV-1 infections...
July 26, 2016: Human Vaccines & Immunotherapeutics
L G Holinka, E Largo, D P Gladue, V O'Donnell, G R Risatti, J L Nieva, M V Borca
: E2, the major envelope glycoprotein of classical swine fever virus (CSFV), is involved in several critical virus functions including cell attachment, host range susceptibility, and virulence in natural hosts. Functional structural analysis of E2 based on Wimley-White interfacial hydrophobicity distribution predicted the involvement of a loop (residues 864-881) stabilized by a disulfide bond ((869)CKWGGNWTCV(878), named FPII) in establishing interactions with the host cell membrane. This loop further contains an (872)GG(873) dipeptide, and two aromatic residues ((871)W and (875)W) accessible to solvent...
September 7, 2016: Journal of Virology
Lisa H Cazares, Michael D Ward, Ernst E Brueggemann, Tara Kenny, Paul Demond, Christopher R Mahone, Karen A O Martins, Jonathan E Nuss, Trevor Glaros, Sina Bavari
BACKGROUND: Ebola virus like particles (EBOV VLPs, eVLPs), are produced by expressing the viral transmembrane glycoprotein (GP) and structural matrix protein VP40 in mammalian cells. When expressed, these proteins self-assemble and bud from 'host' cells displaying morphology similar to infectious virions. Several studies have shown that rodents and non-human primates vaccinated with eVLPs are protected from lethal EBOV challenge. The mucin-like domain of envelope glycoprotein GP1 serves as the major target for a productive humoral immune response...
2016: Clinical Proteomics
Margery A Connelly, Chisato Shimizu, Deborah A Winegar, Irina Shalaurova, Ray Pourfarzib, James D Otvos, John T Kanegaye, Adriana H Tremoulet, Jane C Burns
BACKGROUND: Glycosylation patterns of serum proteins, such as α1-acid glycoprotein, are modified during an acute phase reaction. The response of acute Kawasaki disease (KD) patients to IVIG treatment has been linked to sialic acid levels on native IgG, suggesting that protein glycosylation patterns vary during the immune response in acute KD. Additionally, the distribution and function of lipoprotein particles are altered during inflammation. Therefore, the aim of this study was to explore the potential for GlycA, a marker of protein glycosylation, and the lipoprotein particle profile to distinguish pediatric patients with acute KD from those with other febrile illnesses...
2016: BMC Pediatrics
Jun Arii, Keiko Shindo, Naoto Koyanagi, Akihisa Kato, Yasushi Kawaguchi
: Herpes simplex virus 1 (HSV-1) envelope glycoprotein D (gD) plays an essential role in viral entry. The functional regions of gD responsible for viral entry have been mapped to its extracellular domain, whereas the gD cytoplasmic domain plays no obvious role in viral entry. Thus far, the role(s) of the gD cytoplasmic domain in HSV-1 replication remained to be elucidated. In this study, we showed that ectopic expression of gD induced microvilli-like tubular structures at the plasma membrane, which resembled the reported projection structures of the plasma membrane induced in HSV-1-infected cells...
August 31, 2016: Journal of Virology
Anna Kabanova, Jessica Marcandalli, Tongqing Zhou, Siro Bianchi, Ulrich Baxa, Yaroslav Tsybovsky, Daniele Lilleri, Chiara Silacci-Fregni, Mathilde Foglierini, Blanca Maria Fernandez-Rodriguez, Aliaksandr Druz, Baoshan Zhang, Roger Geiger, Massimiliano Pagani, Federica Sallusto, Peter D Kwong, Davide Corti, Antonio Lanzavecchia, Laurent Perez
Human cytomegalovirus encodes at least 25 membrane glycoproteins that are found in the viral envelope(1). While gB represents the fusion protein, two glycoprotein complexes control the tropism of the virus: the gHgLgO trimer is involved in the infection of fibroblasts, and the gHgLpUL128L pentamer is required for infection of endothelial, epithelial and myeloid cells(2-5). Two reports suggested that gB binds to ErbB1 and PDGFRα (refs 6,7); however, these results do not explain the tropism of the virus and were recently challenged(8,9)...
2016: Nature Microbiology
Jesper Pallesen, Charles D Murin, Natalia de Val, Christopher A Cottrell, Kathryn M Hastie, Hannah L Turner, Marnie L Fusco, Andrew I Flyak, Larry Zeitlin, James E Crowe, Kristian G Andersen, Erica Ollmann Saphire, Andrew B Ward
The Ebola virus (EBOV) GP gene encodes two glycoproteins. The major product is a soluble, dimeric glycoprotein (sGP) that is secreted abundantly. Despite the abundance of sGP during infection, little is known regarding its structure or functional role. A minor product, resulting from transcriptional editing, is the transmembrane-anchored, trimeric viral surface glycoprotein (GP). GP mediates attachment to and entry into host cells, and is the intended target of antibody therapeutics. Because large portions of sequence are shared between GP and sGP, it has been hypothesized that sGP may potentially subvert the immune response or may contribute to pathogenicity...
2016: Nature Microbiology
Christopher D Petro, Brian Weinrick, Nazanin Khajoueinejad, Clare Burn, Rani Sellers, William R Jacobs, Betsy C Herold
A single-cycle herpes simplex virus (HSV) deleted in glycoprotein D (ΔgD-2) elicited high titer HSV-specific antibodies (Abs) that (i) were rapidly transported into the vaginal mucosa; (ii) elicited antibody-dependent cell-mediated cytotoxicity but little neutralization; (iii) provided complete protection against lethal intravaginal challenge; and (iv) prevented establishment of latency in mice. However, clinical isolates may differ antigenically and impact vaccine efficacy. To determine the breadth and further define mechanisms of protection of this vaccine candidate, we tested ΔgD-2 against a panel of clinical isolates in a murine skin challenge model...
August 4, 2016: JCI Insight
Gabriella Campadelli-Fiume, Donna Collins-McMillen, Tatiana Gianni, Andrew D Yurochko
The repertoire of herpesvirus receptors consists of nonintegrin and integrin molecules. Integrins interact with the conserved glycoproteins gH/gL or gB. This interaction is a conserved biology across the Herpesviridae family, likely directed to promote virus entry and endocytosis. Herpesviruses exploit this interaction to execute a range of critical functions that include (a) relocation of nonintegrin receptors (e.g., herpes simplex virus nectin1 and Kaposi's sarcoma-associated herpesvirus EphA2), or association with nonintegrin receptors (i...
September 29, 2016: Annual Review of Virology
Elizabeth A Nelson, Alyson B Barnes, Ronald D Wiehle, Gregory K Fontenot, Thomas Hoenen, Judith M White
The 2014 outbreak of Ebola virus (EBOV) in Western Africa highlighted the need for anti-EBOV therapeutics. Clomiphene is a U.S. Food and Drug Administration (FDA)-approved drug that blocks EBOV entry and infection in cells and significantly protects EBOV-challenged mice. As provided, clomiphene is, approximately, a 60:40 mixture of two stereoisomers, enclomiphene and zuclomiphene. The pharmacokinetic properties of the two isomers vary, but both accumulate in the eye and male reproductive tract, tissues in which EBOV can persist...
2016: Viruses
Zachariah A McIver, Jason M Grayson, Benjamin N Coe, Jacqueline E Hill, Gregory A Schamerhorn, Tymish Y Ohulchanskyy, Michelle K Linder, Kellie S Davies, Roy S Weiner, Michael R Detty
T lymphocytes play a central role in many human immunologic disorders, including autoimmune and alloimmune diseases. In hematopoietic stem cell transplantation, acute graft-versus-host-disease (GVHD) is caused by an attack on the recipient's tissues from donor allogeneic T cells. Selectively depleting GVHD-causing cells prior to transplant may prevent GVHD. In this study, we evaluated 24 chalcogenorhodamine photosensitizers for their ability to selectively deplete reactive T lymphocytes and identified the photosensitizer 2-Se-Cl, which accumulates in stimulated T cells in proportion to oxidative phosphorylation...
September 1, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Lorrie A Burnham, Dinesh Jaishankar, Jeffrey M Thompson, Kevin S Jones, Deepak Shukla, Vaibhav Tiwari
Cationic liposomes are widely used to facilitate introduction of genetic material into target cells during transfection. This study describes a non-receptor mediated herpes simplex virus type-1 (HSV-1) entry into the Chinese hamster ovary (CHO-K1) cells that naturally lack glycoprotein D (gD)-receptors using a commercially available cationic liposome: lipofectamine. Presence of cell surface heparan sulfate (HS) increased the levels of viral entry indicating a potential role of HS in this mode of entry. Loss of viral entry in the presence of actin de-polymerizing or lysosomotropic agents suggests that this mode of entry results in the endocytosis of the lipofectamine-virus mixture...
2016: Frontiers in Microbiology
Gonzalo P Barriga, Fernando Villalón-Letelier, Chantal L Márquez, Eduardo A Bignon, Rodrigo Acuña, Breyan H Ross, Octavio Monasterio, Gonzalo A Mardones, Simon E Vidal, Nicole D Tischler
Hantaviruses can cause hantavirus pulmonary syndrome or hemorrhagic fever with renal syndrome in humans. To enter cells, hantaviruses fuse their envelope membrane with host cell membranes. Previously, we have shown that the Gc envelope glycoprotein is the viral fusion protein sharing characteristics with class II fusion proteins. The ectodomain of class II fusion proteins is composed of three domains connected by a stem region to a transmembrane anchor in the viral envelope. These fusion proteins can be inhibited through exogenous fusion protein fragments spanning domain III (DIII) and the stem region...
July 2016: PLoS Neglected Tropical Diseases
Tom L G M van den Kerkhof, Steven W de Taeye, Brigitte D Boeser-Nunnink, Dennis R Burton, Neeltje A Kootstra, Hanneke Schuitemaker, Rogier W Sanders, Marit J van Gils
BACKGROUND: Current HIV-1 immunogens are unable to induce antibodies that can neutralize a broad range of HIV-1 (broadly neutralizing antibodies; bNAbs). However, such antibodies are elicited in 10-30 % of HIV-1 infected individuals, and the co-evolution of the virus and the humoral immune responses in these individuals has attracted attention, because they can provide clues for vaccine design. RESULTS: Here we characterized the NAb responses and envelope glycoprotein evolution in an HIV-1 infected "elite neutralizer" of the Amsterdam Cohort Studies on HIV-1 infection and AIDS who developed an unusually potent bNAb response rapidly after infection...
2016: Retrovirology
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