scholarly journals Spike Protein Fusion Peptide and Feline Coronavirus Virulence

2012 ◽  
Vol 18 (7) ◽  
pp. 1089-1095 ◽  
Author(s):  
Hui-Wen Chang ◽  
Herman F. Egberink ◽  
Rebecca Halpin ◽  
David J. Spiro ◽  
Peter J.M. Rottier
Keyword(s):  
Fusion Peptide ◽  
Spike Protein ◽  
Protein Fusion ◽  
Feline Coronavirus

scholarly journals Comprehensive characterization of the antibody responses to SARS-CoV-2 Spike protein after infection and/or vaccination

2021 ◽  
Author(s):  
Meghan E. Garrett ◽  
Jared G. Galloway ◽  
Caitlin Wolf ◽  
Jennifer K. Logue ◽  
Nicholas Franko ◽  
...  
Keyword(s):  
Immune Escape ◽  
Severe Disease ◽  
Vaccine Dose ◽  
Principal Component ◽  
Fusion Peptide ◽  
Antibody Binding ◽  
Spike Protein ◽  
Heptad Repeat ◽  
Medical Institute ◽  
Vaccine Type

ABSTRACTBackgroundControl of the COVID-19 pandemic will rely on SARS-CoV-2 vaccine-elicited antibodies to protect against emerging and future variants; an understanding of the unique features of the humoral responses to infection and vaccination, including different vaccine platforms, is needed to achieve this goal.MethodsThe epitopes and pathways of escape for Spike-specific antibodies in individuals with diverse infection and vaccination history were profiled using Phage-DMS. Principal component analysis was performed to identify regions of antibody binding along the Spike protein that differentiate the samples from one another. Within these epitope regions we determined potential escape mutations by comparing antibody binding of peptides containing wildtype residues versus peptides containing a mutant residue.ResultsIndividuals with mild infection had antibodies that bound to epitopes in the S2 subunit within the fusion peptide and heptad-repeat regions, whereas vaccinated individuals had antibodies that additionally bound to epitopes in the N- and C-terminal domains of the S1 subunit, a pattern that was also observed in individuals with severe disease due to infection. Epitope binding appeared to change over time after vaccination, but other covariates such as mRNA vaccine dose, mRNA vaccine type, and age did not affect antibody binding to these epitopes. Vaccination induced a relatively uniform escape profile across individuals for some epitopes, whereas there was much more variation in escape pathways in in mildly infected individuals. In the case of antibodies targeting the fusion peptide region, which was a common response to both infection and vaccination, the escape profile after infection was not altered by subsequent vaccination.ConclusionsThe finding that SARS-CoV-2 mRNA vaccination resulted in binding to additional epitopes beyond what was seen after infection suggests protection could vary depending on the route of exposure to Spike antigen. The relatively conserved escape pathways to vaccine-induced antibodies relative to infection-induced antibodies suggests that if escape variants emerge, they may be readily selected for across vaccinated individuals. Given that the majority of people will be first exposed to Spike via vaccination and not infection, this work has implications for predicting the selection of immune escape variants at a population level.FundingThis work was supported by NIH grants AI138709 (PI Overbaugh) and AI146028 (PI Matsen). Julie Overbaugh received support as the Endowed Chair for Graduate Education (FHCRC). The research of Frederick Matsen was supported in part by a Faculty Scholar grant from the Howard Hughes Medical Institute and the Simons Foundation. Scientific Computing Infrastructure at Fred Hutch was funded by ORIP grant S10OD028685.

scholarly journals An Epitope of the Semliki Forest Virus Fusion Protein Exposed during Virus-Membrane Fusion

1999 ◽  
Vol 73 (12) ◽  
pp. 10029-10039 ◽  
Author(s):  
Anna Ahn ◽  
Matthew R. Klimjack ◽  
Prodyot K. Chatterjee ◽  
Margaret Kielian
Keyword(s):  
Membrane Fusion ◽  
Binding Site ◽  
Semliki Forest Virus ◽  
Fusion Reaction ◽  
Ph Dependence ◽  
Fusion Peptide ◽  
Endocytic Pathway ◽  
Spike Protein ◽  
Viral Fusion ◽  
Wide Range

ABSTRACT Semliki Forest virus (SFV) is an enveloped alphavirus that infects cells via a membrane fusion reaction triggered by acidic pH in the endocytic pathway. Fusion is mediated by the spike protein E1 subunit, an integral membrane protein that contains the viral fusion peptide and forms a stable homotrimer during fusion. We have characterized four monoclonal antibodies (MAbs) specific for the acid conformation of E1. These MAbs did not inhibit fusion, suggesting that they bind to an E1 region different from the fusion peptide. Competition analyses demonstrated that all four MAbs bound to spatially related sites on acid-treated virions or isolated spike proteins. To map the binding site, we selected for virus mutants resistant to one of the MAbs, E1a-1. One virus isolate, SFV 4-2, showed reduced binding of three acid-specific MAbs including E1a-1, while its binding of one acid-specific MAb as well as non-acid-specific MAbs to E1 and E2 was unchanged. The SFV 4-2 mutant was fully infectious, formed the E1 homotrimer, and had the wild-type pH dependence of infection. Sequence analysis demonstrated that the relevant mutation in SFV 4-2 was a change of E1 glycine 157 to arginine (G157R). Decreased binding of MAb E1a-1 was observed under a wide range of assay conditions, strongly suggesting that the E1 G157R mutation directly affects the MAb binding site. These data thus localize an E1 region that is normally hidden in the neutral pH structure and becomes exposed as part of the reorganization of the spike protein to its fusion-active conformation.

scholarly journals Linear epitope landscape of SARS-CoV-2 Spike protein constructed from 1,051 COVID-19 patients

2020 ◽  
Author(s):  
Yang Li ◽  
Mingliang Ma ◽  
Qing Lei ◽  
Feng Wang ◽  
Ziyong Sun ◽  
...  
Keyword(s):  
Cleavage Site ◽  
Fusion Peptide ◽  
Spike Protein ◽  
Linear Epitope ◽  
Peptide Microarray ◽  
Serum Igg ◽  
Immunogenic Peptides ◽  
Linear Epitopes

Neutralization antibodies and vaccines for treating COVID-19 are desperately needed. For precise development of antibodies and vaccines, the key is to understand which part of SARS-CoV-2 Spike protein is highly immunogenic on a systematic way. We generate a linear epitope landscape of Spike protein by analyzing serum IgG response of 1,051 COVID-19 patients with a peptide microarray. We reveal two regions that rich of linear epitopes, i.e., CTD and a region close to the S2' cleavage site and fusion peptide. Unexpectedly, we find RBD is lack of linear epitope. Besides 3 moderate immunogenic peptides from RBD, 16 highly immunogenic peptides from other regions of Spike protein are determined. These peptides could serve as the base for precise development of antibodies and vaccines for COVID-19 on a systematic level.

scholarly journals Role of Sequence and Structure of the Hendra Fusion Protein Fusion Peptide in Membrane Fusion

2012 ◽  
Vol 287 (35) ◽  
pp. 30035-30048 ◽  
Author(s):  
Everett Clinton Smith ◽  
Sonia M. Gregory ◽  
Lukas K. Tamm ◽  
Trevor P. Creamer ◽  
Rebecca Ellis Dutch
Keyword(s):  
Fusion Protein ◽  
Membrane Fusion ◽  
Fusion Peptide ◽  
Protein Fusion

scholarly journals Mutation in Spike Protein Cleavage Site and Pathogenesis of Feline Coronavirus

2013 ◽  
Vol 19 (7) ◽  
pp. 1066-1073 ◽  
Author(s):  
Beth N. Licitra ◽  
Jean K. Millet ◽  
Andrew D. Regan ◽  
Brian S. Hamilton ◽  
Vera D. Rinaldi ◽  
...  
Keyword(s):  
Cleavage Site ◽  
Spike Protein ◽  
Protein Cleavage ◽  
Feline Coronavirus
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