The Chikungunya Virus Capsid Protein Contains Linear B Cell Epitopes in the N- and C-Terminal Regions that are Dependent on an Intact C-Terminus for Antibody Recognition

Human norovirus (HuNoV) is the leading cause of nonbacterial gastroenteritis worldwide with the GII.4 genotype accounting for over 80% of infections. The major capsid protein of GII.4 variants is evolving rapidly, resulting in new epidemic variants with altered antigenic potentials that must be considered for the development of an effective vaccine. In this study, we identify and characterize linear blockade B-cell epitopes in HuNoV GII.4. Five unique linear B-cell epitopes, namely P2A, P2B, P2C, P2D, and P2E, were predicted on the surface-exposed regions of the capsid protein. Evolving of the surface-exposed epitopes over time was found to correlate with the emergence of new GII.4 outbreak variants. Molecular dynamic simulation (MD) analysis and molecular docking revealed that amino acid substitutions in the putative epitopes P2B, P2C, and P2D could be associated with immune escape and the appearance of new GII.4 variants by affecting solvent accessibility and flexibility of the antigenic sites and histo-blood group antigens (HBAG) binding. Testing the synthetic peptides in wild-type mice, epitopes P2B (336–355), P2C (367–384), and P2D (390–400) were recognized as GII.4-specific linear blockade epitopes with the blocking rate of 68, 55 and 28%, respectively. Blocking rate was found to increase to 80% using the pooled serum of epitopes P2B and P2C. These data provide a strategy for expanding the broad blockade potential of vaccines for prevention of NoV infection.

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Antibody recognition of cathepsin L1-derived peptides in Fasciola hepatica-infected and/or vaccinated cattle and identification of protective linear B-cell epitopes

Vaccine ◽

10.1016/j.vaccine.2018.01.020 ◽

2018 ◽

Vol 36 (7) ◽

pp. 958-968 ◽

Cited By ~ 11

Author(s):

Laura Garza-Cuartero ◽

Thomas Geurden ◽

Suman M. Mahan ◽

John M. Hardham ◽

John P. Dalton ◽

...

Keyword(s):

B Cell ◽

Fasciola Hepatica ◽

B Cell Epitopes ◽

Antibody Recognition ◽

Linear B

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Localization of the C terminus of the assembly domain of hepatitis B virus capsid protein: Implications for morphogenesis and organization of encapsidated RNA

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.94.18.9556 ◽

1997 ◽

Vol 94 (18) ◽

pp. 9556-9561 ◽

Cited By ~ 132

Author(s):

A. Zlotnick ◽

N. Cheng ◽

S. J. Stahl ◽

J. F. Conway ◽

A. C. Steven ◽

...

Keyword(s):

Hepatitis B Virus ◽

Hepatitis B ◽

Capsid Protein ◽

Virus Capsid ◽

C Terminus ◽

B Virus ◽

Virus Capsid Protein

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Fine mapping of linear B cell epitopes on capsid protein of porcine circovirus 3

Applied Microbiology and Biotechnology ◽

10.1007/s00253-020-10664-2 ◽

2020 ◽

Vol 104 (14) ◽

pp. 6223-6234

Author(s):

Min Jiang ◽

Junqing Guo ◽

Gaiping Zhang ◽

Qianyue Jin ◽

Yankai Liu ◽

...

Keyword(s):

B Cell ◽

Capsid Protein ◽

Fine Mapping ◽

Porcine Circovirus ◽

B Cell Epitopes ◽

Porcine Circovirus 3 ◽

Linear B

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Mutation of a Conserved Nuclear Export Sequence in Chikungunya Virus Capsid Protein Disrupts Host Cell Nuclear Import

Viruses ◽

10.3390/v9100306 ◽

2017 ◽

Vol 9 (10) ◽

pp. 306 ◽

Cited By ~ 2

Author(s):

Susan Jacobs ◽

Adam Taylor ◽

Lara Herrero ◽

Suresh Mahalingam ◽

John Fazakerley

Keyword(s):

Host Cell ◽

Capsid Protein ◽

Nuclear Import ◽

Nuclear Export ◽

Chikungunya Virus ◽

Virus Capsid ◽

Nuclear Export Sequence ◽

Virus Capsid Protein

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Characterization of Two Novel Linear B-Cell Epitopes in the Capsid Protein of Avian Hepatitis E Virus (HEV) That Are Common to Avian, Swine, and Human HEVs

Journal of Virology ◽

10.1128/jvi.00107-15 ◽

2015 ◽

Vol 89 (10) ◽

pp. 5491-5501 ◽

Cited By ~ 17

Author(s):

Xinjie Wang ◽

Qin Zhao ◽

Lu Dang ◽

Yani Sun ◽

Jiming Gao ◽

...

Keyword(s):

Amino Acid ◽

B Cell ◽

Capsid Protein ◽

Hepatitis E Virus ◽

Hepatitis E ◽

Antigenic Structure ◽

B Cell Epitopes ◽

Avian Hepatitis E Virus ◽

Avian Hev ◽

Linear B

ABSTRACTAntisera raised against the avian hepatitis E virus (HEV) capsid protein are cross-reactive with human and swine HEV capsid proteins. In this study, two monoclonal antibodies (MAbs) against the avian HEV capsid protein, namely, 3E8 and 1B5, were shown to cross-react with the swine HEV capsid protein. The motifs involved in binding both MAbs were identified and characterized using phage display biopanning, peptide synthesis, and truncated or mutated protein expression, along with indirect enzyme-linked immunosorbent assay (ELISA) and Western blotting. The results showed that the I/VPHD motif is a necessary core sequence and that P and H are two key amino acids for recognition by MAb 3E8. The VKLYM/TS motif is the minimal amino acid sequence necessary for recognition by MAb 1B5. Cross-reactivity between the two epitopes and antibodies against avian, swine, and human HEVs in sera showed that both epitopes are common to avian, swine, and human HEVs. In addition, amino acid sequence alignment of the capsid proteins revealed that the key motifs of both novel epitopes are the same in HEVs from different animal species, predicting that they may be common to HEV isolates from boars, rabbits, rats, ferrets, mongooses, deer, and camels as well. Protein modeling analysis showed that both epitopes are at least partially exposed on the surface of the HEV capsid protein. Protective capacity analysis demonstrated that the two epitopes are nonprotective against avian HEV infection in chickens. Collectively, these studies characterize two novel linear B-cell epitopes common to avian, swine, and human HEVs, which furthers the understanding of HEV capsid protein antigenic structure.IMPORTANCEMore and more evidence indicates that the host range diversity of hepatitis E virus (HEV) is a global public health concern. A better understanding of the antigenic structure of the HEV capsid protein may improve disease diagnosis and prevention. In this study, binding site mapping and localization as well as the antigenic biology of two novel linear B-cell epitopes common to several different species of HEV were characterized. These findings partially reveal the antigenic structure of the HEV capsid protein and provide potential applications for the development of diagnostics and interventions for HEV infection.

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Immunodominant linear B cell epitopes in the spike and membrane proteins of SARS-CoV-2 identified by immunoinformatics prediction and immunoassay

Scientific Reports ◽

10.1038/s41598-021-99642-w ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Kanokporn Polyiam ◽

Waranyoo Phoolcharoen ◽

Namphueng Butkhot ◽

Chanya Srisaowakarn ◽

Arunee Thitithanyanont ◽

...

Keyword(s):

B Cell ◽

Cleavage Site ◽

Vaccine Development ◽

Cell Epitope ◽

Epitope Prediction ◽

E Proteins ◽

B Cell Epitopes ◽

C Terminus ◽

B Cell Epitope ◽

Linear B

AbstractSARS-CoV-2 continues to infect an ever-expanding number of people, resulting in an increase in the number of deaths globally. With the emergence of new variants, there is a corresponding decrease in the currently available vaccine efficacy, highlighting the need for greater insights into the viral epitope profile for both vaccine design and assessment. In this study, three immunodominant linear B cell epitopes in the SARS-CoV-2 spike receptor-binding domain (RBD) were identified by immunoinformatics prediction, and confirmed by ELISA with sera from Macaca fascicularis vaccinated with a SARS-CoV-2 RBD subunit vaccine. Further immunoinformatics analyses of these three epitopes gave rise to a method of linear B cell epitope prediction and selection. B cell epitopes in the spike (S), membrane (M), and envelope (E) proteins were subsequently predicted and confirmed using convalescent sera from COVID-19 infected patients. Immunodominant epitopes were identified in three regions of the S2 domain, one region at the S1/S2 cleavage site and one region at the C-terminus of the M protein. Epitope mapping revealed that most of the amino acid changes found in variants of concern are located within B cell epitopes in the NTD, RBD, and S1/S2 cleavage site. This work provides insights into B cell epitopes of SARS-CoV-2 as well as immunoinformatics methods for B cell epitope prediction, which will improve and enhance SARS-CoV-2 vaccine development against emergent variants.

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