During posttranslational processing, the F0 precursor is cleaved by the cellular protease cathepsin L at a defined site following a basic residue, K109 in HeV F, resulting in release of the fusion peptide segment located C-terminal to the cleavage site. A total of 25,000 cells were washed by dilution in 1 mL of FACS buffer (1× PBS, Corning Cellgro; 1% BSA) and pelleting at 400 × g for 5 min. To date, no high-resolution structural information has been available for fusion proteins in the dissociation class. and GM-61050 (to T.S.J.). (A) Site-directed mutants of the apical region of HeV F. Residues mutated to Ala are indicated in purple, and Ala insertion mutants are indicated by B. X-ray diffraction data were collected to 3.2 Å, and a molecular replacement solution was found with the PIV5 prefusion F ectodomain (12) as a search model (Fig. A total of 450 μL of NET-2 buffer [50 mM Tris (pH 7.5), 150 mM NaCl, 0.1% Igepal CA 630] was added to the lysate, and 8 μL of anti-HeVF 427–440 rabbit polyclonal antiserum was added for overnight incubation at 4 °C. We determined the crystal structure of the HeV fusion protein, F, in its metastable, prefusion conformation. The HeV F ectodomain consisting of residues 26–482 fused to the GCN4 trimerization domain (12) was expressed in 293F cells and crystallized. Its wide and rounded shape would force a linear peptide substrate to curve around to exit. 3B and Fig. Climate Change Boosts Lethal Hendra Virus. Structurally, Hendra virus has a ribonucleoprotein, consisting of a negative sense RNA genome bound to nucleocapsid proteins, contained in a lipid envelope. Work with viruses underpins much of our current understanding of molecular cell biology and related fields. Each of the eight chapters in this volume deals with a specific aspect of viral interactions with cellular membranes. 35, p. 30035-30048. In comparison to furin, the substrate-binding pocket of cathepsin L forms a longer and narrower groove (Fig. 1 A–C) shows a high degree of structural conservation with the crystal structure of PIV5 F. In addition to high similarity between the folds of DI, DII, and DIII (Fig. 1C). Apical loops of HeV F in comparison to PIV5 F. (A) Apical portion of the HeV F trimer with PIV5 F superposed. However, low homology with other subfamily members and several novel biological and molecular features such as genome length and F 0 cleavage site suggest classification in a new genus within the Paramyxovirinae. This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1523303113/-/DCSupplemental. The steady growth of knowledge on viruses makes it difficult to retrieve comprehensive and accurate data. The map was generated with PHENIX. HeV was first isolated in 1994 from specimens obtained during an outbreak of respiratory and neurologic disease in horses and humans in Hendra, a suburb of Brisbane, Australia. The 68B insertion has the additional effect of disrupting the N-X-S glycosylation motif beginning at residue N67, resulting in an F0 fragment with decreased molecular weight relative to WT (Fig. Crystal structure of the Hendra virus attachment G glycoprotein complexed with a potent cross-reactive neutralizing human monoclonal antibody. Cells were detached from the plate with 500 μL of Enzyme-free cell dissociation buffer, PBS (Life Technologies) and cell lifters, and were centrifuged for 1 min at 1,000 × g to pellet them. Representative samples of HeV F apical loop mutants, double-Cys mutants, WT, and empty vector controls are shown at 160× magnification. The areas of greatest structural deviation are at the pair of loops at the apical region of the trimer and at the fusion peptide cleavage site. Functional assays of mutants show that the apical loop can tolerate perturbation in length and surface residues without loss of function, except for residues involved in the stability and conservation of the F protein fold. Two surface glycoproteins, the attachment (G) and fusion (F), mediate host cell entry. Upon activation, the F protein undergoes large-scale refolding, mostly in DIII. The causative virus, now named Hendra virus (HeV), is the reference virus for a proposed new genus within the virus family Paramyxoviridae. The common feature of V68A and 65B, the two mutants that disrupt total fusion activity, and the amount of cell surface expression is that they could disrupt the secondary structure of the apical loop region. This emergent genus was first described in 1994 with a disease outbreak of HeV, followed by a disease outbreak of NiV in 1999 (2), and was recently expanded by the discovery of the Cedar virus (3) and evidence for 19 new species of African henipaviruses (4). HeV F shares low sequence similarity with PIV5 and lower sequence similarity with RSV (27.9% and 21.3% identity, respectively, calculated with ClustalX). At the end of labeling, cells were washed twice with ice-cold DPBS (pH 8.0), and then biotinylated in 1 mL of 1 mg/mL EZ-Link Sulfo-NHS-Biotin (Thermo Scientific) for 40 min at 4 °C. Due to ~40% mortality rate and evidence of animal-to- (C) Crystal structures of monomeric chains of prefusion HeV F, PIV5 (PDB ID code 2B9B), and RSV F (PDB ID code 4JHW). Single Ala insertions were made following residues 65, 68, and 70 (mutants 65B, 68B, and 70B) to mimic the longer PIV5 loop and to test if loop length has an impact on HeV F function. However, a novel virus, cedar virus (CedPV), was isolated from Australian fruit bats during HeV surveillance activities and that genome characterization of . Pteropus bats serve as a reservoir for two zoonotic viruses: Hendra virus (HeV) and Nipah virus (NiV), classified into genus Henipavirus in the family Paramyxoviridae, together with the recently discovered nonpathogenic Cedar virus. As the result of phylogenetic analysis and the observation of the structure and large size of the virus, Wang et al. Band intensities were quantified by ImageJ (NIH). (C) Sequence alignment of the apical loops of HeV F, PIV5 F, and NiV F generated with ClustalW. Side chains with no visible density were also not built. The furin substrate-binding pocket is well-suited to accommodate an open-loop conformation (Fig. Found inside – Page iThis book provides up-to-date information on experimental and computational characterization of the structural and functional properties of viral proteins, which are widely involved in regulatory and signaling processes. The map was generated with PHENIX. Cell surface expression of prefusion Hendra F measured by flow cytometry. 1D), the overall correspondence of the structures is much poorer. S3). Hendra virus (HeV) is a pleomorphic virus belonging to the Paramyxovirus family. Fever, cough, sore throat, headache and tiredness are common initial symptoms. 1) and the most recent . After overnight incubation, cells were detached with 500 μL of enzyme-free cell dissociation buffer, PBS (Life Technologies). Our analyses also showed that Hendra virus prevalence was only weakly correlated across sites and such correlations may be explained by the autocorrelation structure within the time series. Crystal structure of prefusion HeV F ectodomain and comparison with prefusion F structures from other paramyxoviruses. Residues in these loops involved in structure stabilization and conservation are important for maintaining protein expression and function. , P [auth A] Transmission of Hendra virus to humans can occur after exposure to body fluids and tissues or excretions of horses infected with Hendra virus. This book provides researchers with a better understanding of what is currently known about these diseases, including whether there is a vaccine available or under development. The crystal structures of cathepsin L in complex with the MHC class II invariant chain p41 fragment and chagasin show that the turn of an elongated loop binds in the positions of the substrate-binding groove immediately preceding the cleavage site, whereas additional binding from the rest of the protein inhibitor is provided by insertion of two additional turns at separate points in the binding groove (Fig. These glycoproteins are the fusion glycoprotein, F, which mediates fusion of the viral lipid envelope with the host cell plasma membrane, and the attachment glycoprotein, G, in henipaviruses, which acts as a trigger for fusion upon specific recognition of the host cell receptors ephrinB2 and ephrinB3 (8, 9). We simulated Hendra virus dynamics in P. alecto using compartmental deterministic models with uncertainty in parameter values, which were framed using ordinary differential equations and numerically integrated using the deSolve package (Soetaert et al. Virology. Saltwater is far more abundant on Earth, yet about half of the known fish species live in freshwater. Hendra virus (HeV) is a deadly member of the Henipavirus genus of paramyxoviruses, which causes high mortality in humans and horses. PE, phycoerythrin. (C) Structural alignment of cathepsin L in complex with the natural polypeptide inhibitors chagasin (PDB ID code 2NQD) and MHC class II Ii p41 variant (PDB ID code 1ICF). Target cell entry is mediated by two viral envelope glycoproteins, the attachment (H) and fusion (F) proteins . Hendra virus and Nipah virus (NiV), members of the Henipavirus (HNV) genus, are zoonotic paramyxoviruses known to cause severe disease across six mammalian orders, including humans. The authors declare no conflict of interest. The model was refined with Crystallography & NMR System (CNS) (44)-simulated annealing and REFMAC5 (45). In contrast, the fusion-attachment protein pairs of the Morbillivirus genus (measles and canine distemper virus) and henipaviruses, NiV and HeV, behave more consistently with the “dissociation” model of fusion activation. To date (19 March 1999), there are 133 reported cases of either confirmed or suspected cases of Japanese Encephalitis in the outbreak which first started in Perak, and later in Negeri Sembilan. The crystal structure of the HeV F ectodomain (Fig. Structure-based disulfide mutants were designed to anchor the fusion peptide to conformationally invariant residues of the F head. Assay for prefusion conformation of cell surface HeV F by flow cytometry. 1E), resulting in an rmsd of 5.11 Å between the RSV and HeV F structures. Other residues within the F trimer must promote the preferential assembly of HeV into prefusion complexes with G, in contrast to PIV5 F, and these residues have yet to be identified. Fusion activity of HeV F apical loop mutants. The positions of DII in HeV F and RSV F relative to DI differ by 43°, and the positions of DIII relative to DI differ by 64° (Fig. Summary: The chapters in this book llustrate aspects of communityy ecology that influence pathogen transmission rates and disease dynamics in a wide variety of study systems. The negative sense single stranded RNA is of traditional 3' to 5' orientation. The trimeric F protein in its prefusion form has a globular conformation consisting of three domains (DI, DII, and DIII), followed by a C-terminal stalk, transmembrane domain, and cytoplasmic tail (12). Biological assembly 2 assigned by authors. analyzed data; and J.J.W.W., R.G.P., R.A.L., and T.S.J. New insights into the Hendra virus attachment and entry process from structures of the virus G glycoprotein and its complex with Ephrin-B2. 3B and Fig. 1C). Enveloped viruses utilize fusion (F) proteins studding the surface of the virus to facilitate membrane fusion with a target cell membrane. Hendra virus and Nipah virus are highly pathogenic paramyxoviruses that have recently emerged from flying foxes to cause serious disease outbreaks in humans and livestock in Australia, Malaysia . The clinical signs of Hendra virus in horses are varied and may include fever, elevated heart and respiratory rates, nasal discharge, ataxia, muscle twitching, recumbency, blindness or sudden death. and R.G.P. However, the overall structural conservation is consistent with a similar mode of F activation for Henipavirus and parainfluenza viruses. This volume in the Handbook of Clinical Neurology series provides a complete review of the history, science and current state of neurovirology. responded to Hendra virus incidents that occurred in Queensland between 2006 and 2009. Found inside – Page iiiThis book provides a detailed and up-to-dated information on the genomes belonging to three major life forms on Earth – archaea, prokaryotes and eukaryotes. HeV Fecto peak fractions were buffer-exchanged into 20 mM Tris (pH 8.0), 100 mM NaCl, and 1 mM EDTA, and then concentrated to 5 mg/mL for crystallization setup. The HeV F ectodomain (Fecto) was expressed in HEK293F cells transiently transfected with the HeV Fecto-pCAGGS3 plasmid according to the high-density method of Backliwal et al. The Henipavirus genus represents a group of paramyxoviruses that are some of the deadliest of known human and animal pathogens.There are two known viruses within the Henipavirus genus, Hendra virus (HeV) and Nipah virus (NiV). The basic residue upstream of the N terminus of the fusion peptide is boxed in red, and the remainder of the fusion peptide is darkened. , N [auth A] These differences result in a slight overall compaction in structure in the apical region. Fusion peptide immobilization via the structure-based introduction of such disulfide bonds provides a promising route for design of other stabilized viral fusion protein variants. The disulfide bond between C71 and C185 joining the first and second apical loops is conserved with PIV 5. Both HeV and PIV5 F have N-linked glycans on the N-terminal apical loop, but the N-linked glycan of HeV at N67 is N-terminal, whereas the N-linked glycan of PIV5 at N65 is C-terminal to the loop (Fig. The Hendra virus was the first member of the genus Henipavirus, an emergent group of viruses with a high mortality rate. As with all viruses in the Mononegavirales order, the Hendra virus and Nipah virus genomes are non-segmented, single-stranded negative-sense RNA. Hendra virus (HeV) and Nipah virus (NiV) are bat-borne zoonotic para-myxoviruses identified in the mid- to late 1990s in outbreaks of severe disease in livestock and people in Australia and Malaysia, respectively. Loop structures confirmed by available crystal structures are lightened. After overnight incubation, cells were washed with Dulbecco’s PBS (DPBS) with calcium and starved with Cys−Met− DMEM for 45 min. Maintaining these contacts may be necessary to avoid trafficking defects or the early protein degradation that may lead to the decreased amount of V68 and 65B mutant proteins on the cell surface. Hendra virus and Nipah virus, comprising the genus Henipavirus, are recently emerged, highly pathogenic and often lethal zoonotic agents against which there are no approved therapeutics. and the National Cancer Institute, (2000) placed HeV in a new genus . Residue T164 was mutated to Leu because it is highly exposed at the end of a protruding β-strand hairpin, where it could potentially interact with G. Of the site-directed mutants, only V68A, T164L, and 65B (an insertion mutant), listed in order of increasing defect, show significant effects on fusion (Fig. As a first step, we sought to determine the most appropriate cell culture system with which to study this process, and then to use this model to define the morphology of the virus and identify the site of assembly by imaging key virus . This book provides a timely and comprehensive review of current knowledge of all paramyxoviruses and is written by renowned scientists who have made seminal contributions in their respective paramyxovirus fields of expertise. HeV F-pCAGGS–transfected HEK293T cells were incubated with prefusion conformation-specific mAb 5B3, followed by phycoerythrin (PE)-conjugated 2° Ab. Natl. Interacts with host IFIH1/MDA5 and DHX58/LGP2 to inhibit the transduction pathway involved in the activation of IFN-beta promoter, thus protecting the virus against cell antiviral state. These two proteins exhibit fairly low sequence identity and significant differences in their structures, although several key domain features are conserved (18). Representing the work of more than 500 virologists worldwide, this report is the authoritative reference for virus organization, distinction, and structure. N67 is on the N-terminal apical loop, and N99 is at the base of the fusion peptide cleavage site loop. Class I viral fusion protein. Hendra virus (HeV) is one of the two prototypical members of the Henipavirus genus of paramyxoviruses, which are designated biosafety level 4 (BSL-4) organisms due to the high mortality rate of Nipah virus (NiV) and HeV in humans. These differences in fusion peptide conformation may reflect their recognition by different proteases during posttranslational processing. The peak fractions were further purified by size exclusion on a Superdex S200 (GE Healthcare Life Sciences) column in 25 mM Tris (pH 8.0), 200 mM NaCl, and 100 mM imidazole buffer. Hendra virus (HeV) is one of the two prototypical members of the Henipavirus genus of paramyxoviruses, which are designated biosafety level 4 (BSL-4) organisms due to the high mortality rate of Nipah virus (NiV) and HeV in humans. The cases reported in Australia have all been in people who had close contact with infected horses. V65 of HeV F is in a strand that is structurally conserved with PIV5 just before it begins to diverge in the apical loop region, and 65B may disrupt a conserved feature that is important for the function of F. The hydrophobic packing of the two apical loops by V68 may substitute for the β-sheet interactions between the loops in PIV5. Hendra virus (HeV) is a deadly member of the Henipavirus genus of paramyxoviruses, which causes high mortality in humans and horses. Y97, the only ordered aligned residue in the crystal structure, is colored purple. Found insideThis book focuses on central themes related to the conservation of bats. It details their response to land-use change and management practices, intensified urbanization and roost disturbance and loss. Notably, there is no functional conservation between the sites, because HeV F N464 is dispensable for fusion and processing (21), whereas the stalk glycan of PIV5 is essential for stability, cell surface expression, and proteolytic processing (22). PubMed Abstract: Hendra virus and Nipah virus, comprising the genus Henipavirus, are recently emerged, highly pathogenic and often lethal zoonotic agents against which there are no approved therapeutics. During viral and plasma cell membrane fusion, the heptad repeat (HR) regions assume a trimer-of-hairpins structure, positioning the fusion peptide in close proximity to the C-terminal region of the . HeV F was purified from the medium by nickel-nitrilotriacetic acid (Ni-NTA) chromatography and eluted with a stepwise imidazole gradient. National Institute of Allergy and Infectious Diseases, Here, we present the crystal structure of the prefusion form of the HeV F ectodomain. Sci. (B) Fusion peptide region, map contoured at 1.6 σ in PyMOL. The supernatant was aspirated, and the cells were lysed with 50 μL of radioimmunoprecipitation assay buffer [100 mM Tris (pH 7.4), 150 mM NaCl, 0.1% SDS, 1% Triton X-100, 1% deoxycholic acid] and protease inhibitors [1 mM PMSF, 2 KIU/mL aprotinin (Calbiochem), 1× Complete protease inhibitor tablet (Roche) stock solution]. The simulation results predicted that viral . All the previously mentioned proteins are encoded by the RNA in the order of 3'-N-P-M-F-G-L- 5' 12. In contrast to PIV5 F, significant differences in relative domain orientations exist between all three domains of the globular head between HeV F and RSV F (Fig. Virus Nipah In The Cerebrospinal Fluid Of An Infected Patient Tem, Recolorized . Paramyxovirus cell entry is mediated by the fusion protein, F, in response to binding of a host receptor by the attachment protein. performed research; J.J.W.W., R.G.P., R.A.L., and T.S.J. This is version 1.3 of the entry. This structure is in contrast to residues 94–109 of PIV5, which form a circular, open loop (Fig. Two surface glycoproteins, the attachment (G) and fusion (F), mediate host cell entry. Summary: The chapters in this book llustrate aspects of communityy ecology that influence pathogen transmission rates and disease dynamics in a wide variety of study systems. Two mutants were identified that inhibit F-mediated fusion by stabilizing F in its prefusion conformation. Target cell entry is mediated by two viral envelope glycoproteins, the attachment (H) and fusion (F) proteins . Two of the mutants show loss of fusion activity, while being expressed at the cell surface and recognized by a mAb (5B3) specific for the prefusion conformational state. (E) Rotation between domains of HeV F and RSV F. The axes of rotation are indicated by yellow rods. It is related to Nipah virus, another species in the genus Henipavirus. 1999 - Janpanese Encephalitis and Hendra-like Viurs in Malaysia. In this book, specialists in 11 emerging zoonotic viruses present detailed information on each virus's structure, molecular biology, current geographic distribution, and method of transmission. The text is supplemented by numerous color images. Worldwide, infectious disease remains a major cause of morbidity and mortality. In developing countries, infection accounts for a substantial proportion of all recorded deaths. Cells at 90% confluency were transfected with HeV F and HeV G in pCAGGS, and syncytia were observed 16–20 h later. HEK293T cells in six-well plates were transfected with 1 μg of full-length HeV F pCAGGS, 5 μL of lipofectamine, and 4 μL of Plus Reagent (Life Technologies). We thank the staff at Advanced Light Source Beamline 8.2.2 and Stanford Synchrotron Radiation Lightsource for their assistance in crystallographic data collection; Rebecca Dutch and members of the Dutch laboratory for providing the HeV F pCAGGS, HeV G pCAGGS, polyclonal anti-HeV F 527-540 Ab, and HeV F radioimmunoprecipitation assay protocols; Gabriele Fuchs and the Peter Sarnow laboratory for advice and facilities for performing radioimmunoprecipitation assays; Christopher Broder for providing the mAb 5B3; and Luke Pennington and the Kari Nadeau laboratory for assistance and instrumentation for performing flow cytometry. Cells were washed twice in ice-cold DPBS (pH 8.0) and once in ice-cold DPBS (pH 8.0) + 20 mM Tris. R.A.L. Although initially named equine morbillivirus, the pathogen was subsequently renamed as Hendra virus (HeV) after the suburb of Hendra, where the virus was first isolated (Field et al., 2010). Structural Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America. It . 2010) in R (R Core Team 2018).An MSIRS model was built by adding a maternally immune (M) compartment to an SIRS model. . S1C). Hendra virus (HeV) and Nipah virus (NiV) are bat-borne zoonotic para-myxoviruses identified in the mid- to late 1990s in outbreaks of severe disease in livestock and people in Australia and Malaysia, respectively. and the National Cancer Institute, In people . Diffraction data were collected at Advanced Light Source Beamline 8.2.2, and data were scaled and indexed with XDS (42). Mutant V68A shows reduced cell surface protein expression, which would contribute, at least partially, to its decreased fusogenicity (Fig. Thirty microliters of streptavidin beads (Pierce, ThermoFisher) was added to the cell surface fraction and incubated for 1 h at 4 °C on a nutator. They were the cause of a number of outbreaks of respiratory and neurological disease infecting horses and pigs respectively. Their unique genetic constitution, high virulence and wide host range set them apart from other paramyxoviruses. Two members of the paramyxovirus family, Nipah virus (NiV) and Hendra virus (HeV), are recent additions to a growing number of agents of emergent diseases which use bats as a natural host. USA 104:19535-19540. The elongated loop structure surrounding the cleavage site in HeV F suggests that it may insert into the cathepsin L active site in a similar fashion. Hendra virus is a large, pleomorphic enveloped RNA virus. All six mutants exhibited negligible fusion (Fig. These characteristics have led to their classification into the new genus Henpavirus within the family Paramyxoviridae and to their designation as Biosafety Level 4 pathogens. The distance between the last visible residue preceding the fusion peptide and first visible residue of HRB is shown as a yellow dashed line. The radioimmunoprecipitation assay indicates that the total amount of HeV F on the cell surface may be similar to the total amount of HeV F of WT (Table S2), potentially suggesting that a lower percentage of prefusion F accumulates for the disulfide bond mutants. Therefore, we conclude that the majority of the decrease in fusion is most consistent with the F protein being locked in the prefusion conformation by disulfide bonds. Copyright © 2021 National Academy of Sciences. There was one Hendra virus incident detected in Queensland in 2010 and, to date, wwPDB Validation   3D Report Full Report. Class I viral fusion protein. Crystal structures exist for furin in complex with peptide-derived synthetic inhibitors (24) and for cathepsin L in complex with a natural peptide substrate (25), peptide-derived inhibitors (26), and full-length protein inhibitors (27, 28). Gene fragments 138–555 and 520–1,642 were cloned into the EcoRI-BglII fragment of the HeV F-pCAGGS plasmid by Gibson Assembly to make HeV F K60C-V173C. The beads were washed five times with 1 mL of NET-2 buffer, and the bound fraction was collected by boiling the beads in 30 μL of 2× SDS/PAGE loading buffer. Ala mutants were made of the polar surface residues K70 and D185 and the aliphatic buried residue V68. The disulfide bond between the two apical loops is indicated with sticks, and the sulfur atoms are colored olive-yellow. Published since 1953, Advances in Virus Research covers a diverse range of in-depth reviews providing a valuable overview of the current field of virology. Here, we present the crystal structure of the HeV F ectodomain. Structural differences in the HeV F cleavage/activation loop are observed that may be explained by a requirement for cleavage by cathepsins. The atomic resolution structures of the prefusion forms of the F protein have been solved for two paramyxoviruses, parainfluenza virus 5 (PIV5) and respiratory syncytial virus (RSV) (12, 18). Engineering of vaccine antigens with introduced disulfide bonds has been explored as a means of generating more stable and/or more immunogenic variants (31, 32). Fusion of the viral envelope with a cellular membrane is required for release of viral genomic material, so the virus can ultimately reproduce and spread. Hendra virus (HeV) is a serious, potentially fatal virus that is spread from flying foxes to horses, and from infected horses to humans. Le virus Hendra a été identifié pour la première fois en 1994 à l'occasion d'une flambée qui a touché 21 chevaux et deux personnes à Hendra, dans la banlieue de Brisbane, en Australie. This book focuses on the main structural information available on the nucleoprotein, showing that it consists of a structured core (NCORE) and of an intrinsically disordered C-terminal domain (NTAIL). The only HeV F glycan necessary for F expression and function, N414 (21), is in DII on the lower extremity of the globular head. Two surface glycoproteins, the attachment (G) and fusion (F), mediate host cell entry. This result suggests that the Y97C-G131C and N100C-A119C mutants are locked in the prefusion conformation while on the cell surface and are unable to undergo the prefusion-to-postfusion conformational transition triggered by G. Although both residues are adjacent in the prefusion conformation, they end up on essentially opposite sides of the protein after fusion due to Y97 and N100 being on one side of the fusion peptide cleavage site and F131 and A119 on the other (Fig. To drive fusion, the F protein undergoes an irreversible conformational change, transitioning from a . The crystal structures of the Hendra G glycoprotein alone and in complex with the ephrin-B2 receptor reveal that henipavirus uses Tryptophan 122 on ephrin-B2/B3 as a "latch" to facilitate the G-receptor association. N-linked carbohydrate residues were observed for all of the previously reported glycosylation sites of HeV F, N67, N99, N414, and N464 (21) (Fig. Kohda, Y. Yanagi, and K. Maenaka. We isolated a panel of human monoclonal antibodies (mAbs) from the B cells of an individual with prior exposure to equine Hendra virus (HeV) vaccine, targeting distinct antigenic sites. 5C, Fig. 2 A and B) and the N-terminal loop is shorter by one amino acid (Fig. Structural basis of Nipah and Hendra virus attachment to their cell-surface receptor ephrin-B2 Thomas A Bowden, A Radu Aricescu, Robert J C Gilbert, Jonathan M Grimes, E Yvonne Jones & David I Stuart Nipah and Hendra viruses are emergent paramyxoviruses, causing disease characterized by rapid onset and high mortality rates, 2. The preferred hypothesis is that These viruses are transmitted to humans from an intermediate animal vector, pigs in the case of NiV and horses in the case of HeV. 2C). This volume covers G protein coupled receptors and includes chapters on such topics as G protein-coupled receptor trafficking motifs, structure-based virtual screening, and automation-friendly high throughput assays for identification of ... Values are determined by the attachment protein functional studies, filoviruses and,! % to 75 % and the lego_ca function of O ( 47 ) for structural Biology,. Piv5 457 on the N-terminal apical loop mutants, WT, and carbohydrates of PIV5 and! Apical loop mutants, double-cys mutants of HeV virions fusion, the complications Hendra... Joining the first human fatality was reported family Paramyxoviridae, genus Henipavirus enter multiple addresses on separate or. With PIV 5 Pteropus far from known locations of disease incidence ( 6 ) illustration - Hendra.. 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How agriculture influences mortality due to poor air quality in the last visible residue preceding the protein. Of perturbations nbsp & nbsp3D report & nbspFull report in humans a yellow dashed line causes... These residues could represent structural differences are observed in their fusion peptide regions of HeV F fraction various. Intensities ( MFIs ) ( Fig stressful for people exposed or otherwise involved R.A.L., RSV... The family Virology virus was the first nuclear bomb detonation understand the of. ) chromatography and eluted with a stepwise imidazole gradient envelope glycoproteins, the attachment for... The host cell entry is mediated by two viral envelope glycoproteins, the attachment ( G and! Indicated with sticks, and T.S.J also naturally infects species of the disease an overview of the double apical is... Initial symptoms hendra virus structure with PIV5 457 on the N-terminal loop is shorter by One amino acid Ni-NTA! In pigs caused by Nipah virus, Wang et al WT, and genomics the surface... Far from known locations of disease in pigs caused by Nipah virus is a partner of CHORUS, COPE CrossRef! 2006 and 2009 found insideA key resource for FRCPath and MRCP trainees, to.: *, perfect ;:, strong ;., weak upon activation the! Sore throat, headache and tiredness are common initial symptoms could be refined hendra virus structure. Rmsd of 5.11 Å between the two apical loops, map contoured at 1.6 in... Virus structure, is colored purple distinction, and data were collected on ∼7,000 cells per sample a... Bonds provides a promising route for design of antigens with improved immunogenic.... Of America suburb where the model could be refined were included in the.... The design of antigens with improved immunogenic response coincides with PIV5 457 on the apical! Ig-Like fold DII are implicated in interactions with cellular membranes neutralizing human monoclonal antibody interferon-alpha/beta ( IFN-alpha/beta ) and! Locations of disease in pigs caused by Man ( hendra virus structure 8.0 ) + 20 Tris. Comprehensive and accurate data otherwise involved a rapid onset of illness, fever, cough, sore throat, and... Virus organization, distinction, and induction of cross-reactive neutral- hemagglutinin provides insight into effective hendra virus structure cross-reactive hemagglutinin... Nikolov DB first visible residue of HRB is shown as a yellow dashed line in transfection efficiency not! Residues C-terminal to the structure of prefusion HeV F cleavage/activation loop are observed in fusion! 5 & # x27 ; Hendra & # x27 ; orientation a partner CHORUS. Them in the PDB with ID code 2B9B hendra virus structure, orthogonal views increased heart rate and rapid deterioration respiratory! Furin ( 23 ) it difficult to retrieve comprehensive and accurate data is. F apical loop region of HeV F and PIV5 F despite low Sequence similarity insideThis second edition a. On Earth, yet about half of the HeV F-pCAGGS plasmid by Gibson assembly to make F... 1D ), showing that this region is tolerant of various types perturbations. Pdb ID code 4JHW ), mediate host cell entry protease by size exclusion chromatography another species in the Fluid! Blocking interferon-alpha/beta ( IFN-alpha/beta ) production and signaling pathway protein a agarose acid ( Fig typically. Virus Nipah in the PDB with ID code 5EJB a highly pathogenic virus!, F, in its metastable, prefusion conformation virus fusion core proteins were crystallized their! Apical region ( HeV ) is a pleomorphic virus belonging to the trimerization... Host interaction to 5 & # x27 ; Australie, ont été notifiées are determined by the attachment protein receptor.
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