scholarly journals A Novel Receptor-induced Activation Site in the Nipah Virus Attachment Glycoprotein (G) Involved in Triggering the Fusion Glycoprotein (F)

2008 ◽  
Vol 284 (3) ◽  
pp. 1628-1635 ◽  
Author(s):  
Hector C. Aguilar ◽  
Zeynep Akyol Ataman ◽  
Vanessa Aspericueta ◽  
Angela Q. Fang ◽  
Matthew Stroud ◽  
...  
Keyword(s):  
Nipah Virus ◽  
Virus Attachment ◽  
Glycoprotein G ◽  
Fusion Glycoprotein ◽  
Activation Site

scholarly journals A Quantitative and Kinetic Fusion Protein-Triggering Assay Can Discern Distinct Steps in the Nipah Virus Membrane Fusion Cascade

2010 ◽  
Vol 84 (16) ◽  
pp. 8033-8041 ◽  
Author(s):  
Hector C. Aguilar ◽  
Vanessa Aspericueta ◽  
Lindsey R. Robinson ◽  
Karen E. Aanensen ◽  
Benhur Lee
Keyword(s):  
Membrane Fusion ◽  
Receptor Binding ◽  
Nipah Virus ◽  
Heptad Repeat ◽  
Critical Parameters ◽  
Second Phase ◽  
Two Phase ◽  
Glycoprotein G ◽  
Fusion Glycoprotein ◽  
Functional Features

ABSTRACT The deadly paramyxovirus Nipah virus (NiV) contains a fusion glycoprotein (F) with canonical structural and functional features common to its class. Receptor binding to the NiV attachment glycoprotein (G) triggers F to undergo a two-phase conformational cascade: the first phase progresses from a metastable prefusion state to a prehairpin intermediate (PHI), while the second phase is marked by transition from the PHI to the six-helix-bundle hairpin. The PHI can be captured with peptides that mimic F's heptad repeat regions, and here we utilized a NiV heptad repeat peptide to quantify PHI formation and the half-lives (t 1/2) of the first and second fusion cascade phases. We found that ephrinB2 receptor binding to G triggered ∼2-fold more F than that triggered by ephrinB3, consistent with the increased rate and extent of fusion observed with ephrinB2- versus ephrinB3-expressing cells. In addition, for a series of hyper- and hypofusogenic F mutants, we quantified F-triggering capacities and measured the kinetics of their fusion cascade phases. Hyper- and hypofusogenicity can each be manifested through distinct stages of the fusion cascade, giving rise to vastly different half-lives for the first (t 1/2, 1.9 to 7.5 min) or second (t 1/2, 1.5 to 15.6 min) phase. While three mutants had a shorter first phase and a longer second phase than the wild-type protein, one mutant had the opposite phenotype. Thus, our results reveal multiple critical parameters that govern the paramyxovirus fusion cascade, and our assays should help efforts to elucidate other class I membrane fusion processes.

scholarly journals Proteome Based Approach Defines Candidates for Designing a Multitope Vaccine against the Nipah Virus

2021 ◽  
Vol 22 (17) ◽  
pp. 9330 ◽  
Author(s):  
Mohamed A. Soltan ◽  
Muhammad Alaa Eldeen ◽  
Nada Elbassiouny ◽  
Ibrahim Mohamed ◽  
Dalia A. El-damasy ◽  
...  
Keyword(s):  
Nipah Virus ◽  
Epitope Prediction ◽  
Dynamics Simulation ◽  
World Health ◽  
Effective Vaccine ◽  
Emerging Viruses ◽  
Glycoprotein G ◽  
Fusion Glycoprotein ◽  
Physicochemical Features ◽  
Health Organization

Nipah virus is one of the most harmful emerging viruses with deadly effects on both humans and animals. Because of the severe outbreaks, in 2018, the World Health Organization focused on the urgent need for the development of effective solutions against the virus. However, up to date, there is no effective vaccine against the Nipah virus in the market. In the current study, the complete proteome of the Nipah virus (nine proteins) was analyzed for the antigenicity score and the virulence role of each protein, where we came up with fusion glycoprotein (F), glycoprotein (G), protein (V), and protein (W) as the candidates for epitope prediction. Following that, the multitope vaccine was designed based on top-ranking CTL, HTL, and BCL epitopes from the selected proteins. We used suitable linkers, adjuvant, and PADRE peptides to finalize the constructed vaccine, which was analyzed for its physicochemical features, antigenicity, toxicity, allergenicity, and solubility. The designed vaccine passed these assessments through computational analysis and, as a final step, we ran a docking analysis between the designed vaccine and TLR-3 and validated the docked complex through molecular dynamics simulation, which estimated a strong binding and supported the nomination of the designed vaccine as a putative solution for Nipah virus. Here, we describe the computational approach for design and analysis of this vaccine.

Structural comparison of the cleavage-activation site of the fusion glycoprotein between virulent and avirulent strains of newcastle disease virus

Virology ◽  
1987 ◽  
Vol 158 (1) ◽  
pp. 242-247 ◽  
Author(s):  
Tetsuya Toyoda ◽  
Takemasa Sakaguchi ◽  
Kunitoshi Imai ◽  
Noel Mendoza Inocencio ◽  
Bin Gotoh ◽  
...  
Keyword(s):  
Newcastle Disease Virus ◽  
Disease Virus ◽  
Newcastle Disease ◽  
Structural Comparison ◽  
Fusion Glycoprotein ◽  
Activation Site

scholarly journals Inhibition of henipavirus infection by Nipah virus attachment glycoprotein occurs without cell-surface downregulation of ephrin-B2 or ephrin-B3

2007 ◽  
Vol 88 (2) ◽  
pp. 582-591 ◽  
Author(s):  
Bevan Sawatsky ◽  
Allen Grolla ◽  
Nina Kuzenko ◽  
Hana Weingartl ◽  
Markus Czub
Keyword(s):  
Cell Surface ◽  
Nipah Virus ◽  
Functional Expression ◽  
Hendra Virus ◽  
Pcr Analysis ◽  
Protein G ◽  
Attachment Protein ◽  
Genetic Characteristics ◽  
Virus Attachment ◽  
Fusion Inhibition

Nipah virus (NiV) and Hendra virus (HeV) are newly identified members of the family Paramyxoviridae and have been classified in the new genus Henipavirus based on unique genetic characteristics distinct from other paramyxoviruses. Transgenic cell lines were generated that expressed either the attachment protein (G) or the fusion protein (F) of NiV. Functional expression of NiV F and G was verified by complementation with the corresponding glycoprotein, which resulted in the development of syncytia. When exposed to NiV and HeV, expression of NiV G in Crandall feline kidney cells resulted in a qualitative inhibition of both cytopathic effect (CPE) and cell death by both viruses. RT-PCR analysis of surviving exposed cells showed a complete absence of viral positive-sense mRNA and genomic negative-sense viral RNA. Cells expressing NiV G were also unable to fuse with cells co-expressing NiV F and G in a fluorescent fusion inhibition assay. Cell-surface staining for the cellular receptors for NiV and HeV (ephrin-B2 and ephrin-B3) indicated that they were located on the surface of cells, regardless of NiV G expression or infection by NiV. These results indicated that viral interference can be established for henipaviruses and requires only the expression of the attachment protein, G. Furthermore, it was found that this interference probably occurs at the level of virus entry, as fusion was not observed in cells expressing NiV G. Finally, expression of NiV G by either transient transfection or NiV infection did not alter the cell-surface levels of the two known viral receptors.

scholarly journals Features of the Human Antibody Response against the Respiratory Syncytial Virus Surface Glycoprotein G

Vaccines ◽  
2020 ◽  
Vol 8 (2) ◽  
pp. 337
Author(s):  
Kristina Borochova ◽  
Katarzyna Niespodziana ◽  
Katarina Stenberg Hammar ◽  
Marianne van Hage ◽  
Gunilla Hedlin ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Surface Glycoprotein ◽  
Trigger Factor ◽  
Human Antibody ◽  
Th2 Response ◽  
Virus Surface ◽  
Virus Attachment ◽  
Peptide Epitopes ◽  
Glycoprotein G ◽  
Syncytial Virus

Respiratory syncytial virus (RSV) infections are a major cause of serious respiratory disease in infants. RSV occurs as two major subgroups A and B, which mainly differ regarding the surface glycoprotein G. The G protein is important for virus attachment and G-specific antibodies can protect against infection. We expressed the surface-exposed part of A2 strain-derived G (A2-G) in baculovirus-infected insect cells and synthesized overlapping peptides spanning complete A2-G. The investigation of the natural IgG response of adult subjects during a period of one year showed that IgG antibodies (i) recognize G significantly stronger than the fusion protein F0, (ii) target mainly non-conformational, sequential peptide epitopes from the exposed conserved region but also buried peptides, and (iii) exhibit a scattered but constant recognition profile during the observation period. The IgG subclass reactivity profile (IgG1 > IgG2 > IgG4 = IgG3) was indicative of a mixed Th1/Th2 response. Two strongly RSV-neutralizing sera including the 1st WHO standard contained high IgG anti-G levels. G-specific IgG increased strongly in children after wheezing attacks suggesting RSV as trigger factor. Our study shows that RSV G and G-derived peptides are useful for serological diagnosis of RSV-triggered exacerbations of respiratory diseases and underlines the importance of G for development of RSV-neutralizing vaccines.

scholarly journals Third Helical Domain of the Nipah Virus Fusion Glycoprotein Modulates both Early and Late Steps in the Membrane Fusion Cascade

2020 ◽  
Vol 94 (19) ◽  
Author(s):  
J. Lizbeth Reyes Zamora ◽  
Victoria Ortega ◽  
Gunner P. Johnston ◽  
Jenny Li ◽  
Nicole M. André ◽  
...  
Keyword(s):  
Membrane Fusion ◽  
Host Range ◽  
Viral Entry ◽  
Nipah Virus ◽  
Fusion Process ◽  
Fusion Pore ◽  
Animal Pathogens ◽  
Fusion Glycoprotein ◽  
Helical Region

ABSTRACT Medically important paramyxoviruses, such as measles, mumps, parainfluenza, Nipah, and Hendra viruses, infect host cells by directing fusion of the viral and cellular plasma membranes. Upon infection, paramyxoviruses cause a second type of membrane fusion, cell-cell fusion (syncytium formation), which is linked to pathogenicity. Host cell receptor binding causes conformational changes in the attachment glycoprotein (HN, H, or G) that trigger a conformational cascade in the fusion (F) glycoprotein that mediates membrane fusion. F, a class I fusion protein, contains the archetypal heptad repeat regions 1 (HR1) and 2 (HR2). It is well established that binding of HR1 and HR2 is key to fusing viral and cellular membranes. In this study, we uncovered a novel fusion-modulatory role of a third structurally conserved helical region (HR3) in F. Based on its location within the F structure, and structural differences between its prefusion and postfusion conformations, we hypothesized that the HR3 modulates triggering of the F conformational cascade (still requiring G). We used the deadly Nipah virus (NiV) as an important paramyxoviral model to perform alanine scan mutagenesis and a series of multidisciplinary structural/functional analyses that dissect the various states of the membrane fusion cascade. Remarkably, we found that specific residues within the HR3 modulate not only early F-triggering but also late extensive fusion pore expansion steps in the membrane fusion cascade. Our results characterize these novel fusion-modulatory roles of the F HR3, improving our understanding of the membrane fusion process for NiV and likely for the related Henipavirus genus and possibly Paramyxoviridae family members. IMPORTANCE The Paramyxoviridae family includes important human and animal pathogens, such as measles, mumps, and parainfluenza viruses and the deadly henipaviruses Nipah (NiV) and Hendra (HeV) viruses. Paramyxoviruses infect the respiratory tract and the central nervous system (CNS) and can be highly infectious. Most paramyxoviruses have a limited host range. However, the biosafety level 4 NiV and HeV are highly pathogenic and have a wide mammalian host range. Nipah viral infections result in acute respiratory syndrome and severe encephalitis in humans, leading to 40 to 100% mortality rates. The lack of licensed vaccines or therapeutic approaches against NiV and other important paramyxoviruses underscores the need to understand viral entry mechanisms. In this study, we uncovered a novel role of a third helical region (HR3) of the NiV fusion glycoprotein in the membrane fusion process that leads to viral entry. This discovery sets HR3 as a new candidate target for antiviral strategies for NiV and likely for related viruses.

scholarly journals A Soluble Version of Nipah Virus Glycoprotein G Delivered by Vaccinia Virus MVA Activates Specific CD8 and CD4 T Cells in Mice

Viruses ◽  
2019 ◽  
Vol 12 (1) ◽  
pp. 26 ◽  
Author(s):  
Georgia Kalodimou ◽  
Svenja Veit ◽  
Sylvia Jany ◽  
Ulrich Kalinke ◽  
Christopher C. Broder ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Immune Responses ◽  
Vaccinia Virus ◽  
G Protein ◽  
Nipah Virus ◽  
Cell Responses ◽  
Cellular Immune Responses ◽  
Glycoprotein G ◽  
Cellular Immune

Nipah virus (NiV) is an emerging zoonotic virus that is transmitted by bats to humans and to pigs, causing severe respiratory disease and often fatal encephalitis. Antibodies directed against the NiV-glycoprotein (G) protein are known to play a major role in clearing NiV infection and in providing vaccine-induced protective immunity. More recently, T cells have been also shown to be involved in recovery from NiV infection. So far, relatively little is known about the role of T cell responses and the antigenic targets of NiV-G that are recognized by CD8 T cells. In this study, NiV-G protein served as the target immunogen to activate NiV-specific cellular immune responses. Modified Vaccinia virus Ankara (MVA), a safety-tested strain of vaccinia virus for preclinical and clinical vaccine research, was used for the generation of MVA–NiV-G candidate vaccines expressing different versions of recombinant NiV-G. Overlapping peptides covering the entire NiV-G protein were used to identify major histocompatibility complex class I/II-restricted T cell responses in type I interferon receptor-deficient (IFNAR−/−) mice after vaccination with the MVA–NiV-G candidate vaccines. We have identified an H2-b-restricted nonamer peptide epitope with CD8 T cell antigenicity and a H2-b 15mer with CD4 T cell antigenicity in the NiV-G protein. The identification of this epitope and the availability of the MVA–NiV-G candidate vaccines will help to evaluate NiV-G-specific immune responses and the potential immune correlates of vaccine-mediated protection in the appropriate murine models of NiV-G infection. Of note, a soluble version of NiV-G was advantageous in activating NiV-G-specific cellular immune responses using these peptides.

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