Comprehensive profiling of neutralizing polyclonal sera targeting coxsackievirus B3.


Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
12 10 2023
Historique:
received: 28 01 2023
accepted: 28 09 2023
medline: 23 10 2023
pubmed: 13 10 2023
entrez: 12 10 2023
Statut: epublish

Résumé

Despite their fundamental role in resolving viral infections, our understanding of how polyclonal neutralizing antibody responses target non-enveloped viruses remains limited. To define these responses, we obtained the full antigenic profile of multiple human and mouse polyclonal sera targeting the capsid of a prototypical picornavirus, coxsackievirus B3. Our results uncover significant variation in the breadth and strength of neutralization sites targeted by individual human polyclonal responses, which contrasted with homogenous responses observed in experimentally infected mice. We further use these comprehensive antigenic profiles to define key structural and evolutionary parameters that are predictive of escape, assess epitope dominance at the population level, and reveal a need for at least two mutations to achieve significant escape from multiple sera. Overall, our data provide a comprehensive analysis of how polyclonal sera target a non-enveloped viral capsid and help define both immune dominance and escape at the population level.

Identifiants

pubmed: 37828013
doi: 10.1038/s41467-023-42144-2
pii: 10.1038/s41467-023-42144-2
pmc: PMC10570382
doi:

Substances chimiques

Antibodies, Viral 0
Antibodies, Neutralizing 0
Epitopes 0
Capsid Proteins 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

6417

Informations de copyright

© 2023. Springer Nature Limited.

Références

Corti, D. & Lanzavecchia, A. Broadly neutralizing antiviral antibodies. Annu Rev. Immunol. 31, 705–742 (2013).
doi: 10.1146/annurev-immunol-032712-095916 pubmed: 23330954
Huang, D. B., Wu, J. J. & Tyring, S. K. A review of licensed viral vaccines, some of their safety concerns, and the advances in the development of investigational viral vaccines. J. Infect. 49, 179–209 (2004).
doi: 10.1016/j.jinf.2004.05.018 pubmed: 15337336 pmcid: 7126106
Burton, D. R. Antibodies, viruses and vaccines. Nat. Rev. Immunol. 2, 706–713 (2002).
doi: 10.1038/nri891 pubmed: 12209139
Liu, T., Wang, Y., Tan, T. J. C., Wu, N. C. & Brooke, C. B. The evolutionary potential of influenza A virus hemagglutinin is highly constrained by epistatic interactions with neuraminidase. Cell Host Microbe 30, 1363–1369.e4 (2022).
doi: 10.1016/j.chom.2022.09.003 pubmed: 36150395 pmcid: 9588755
Greaney, A. J. et al. Antibodies elicited by mRNA-1273 vaccination bind more broadly to the receptor binding domain than do those from SARS-CoV-2 infection. Sci. Transl. Med. 13, eabi9915 (2021).
Greaney, A. J. et al. Mapping mutations to the SARS-CoV-2 RBD that escape binding by different classes of antibodies. Nat. Commun. 12, 4196 (2021).
doi: 10.1038/s41467-021-24435-8 pubmed: 34234131 pmcid: 8263750
Greaney, A. J. et al. Complete mapping of mutations to the SARS-CoV-2 spike receptor-binding domain that escape antibody recognition. Cell Host Microbe 29, 44–57.e9 (2021).
doi: 10.1016/j.chom.2020.11.007 pubmed: 33259788 pmcid: 7676316
Dingens, A. S. et al. High-resolution mapping of the neutralizing and binding specificities of polyclonal sera post hiv env trimer vaccination. Elife 10, 1–32 (2021).
doi: 10.7554/eLife.64281
Lee, J. M. et al. Mapping person-to-person variation in viral mutations that escape polyclonal serum targeting influenza hemagglutinin. Elife 8, 1–28 (2019).
doi: 10.7554/eLife.49324
Valero-Rello, A. & Sanjuán, R. Enveloped viruses show increased propensity to cross-species transmission and zoonosis. Proc. Natl. Acad. Sci. 119, e2215600119 (2022).
Li, Y. et al. The importance of glycans of viral and host proteins in enveloped virus infection. Front. Immunol. 12, 638573 (2021).
Rossmann, M. G. et al. Structure of a human common cold virus and functional relationship to other picornaviruses. Nature 317, 145–153 (1985).
doi: 10.1038/317145a0 pubmed: 2993920
Racaniello, V. R. Picornaviridae: the viruses and their replication. Fields Virol. 1, 453–489 (2013).
Levy, H., Bostina, M., Filman, D. J. & Hogle, J. M. Cell Entry: a biochemical and structural perspective. In: The Picornaviruses 87–104 (ASM Press). https://doi.org/10.1128/9781555816698.ch6 , (2014).
Martín, J., Crossland, G., Wood, D. J. & Minor, P. D. Characterization of formaldehyde-inactivated poliovirus preparations made from live-attenuated strains. J. Gen. Virol. 84, 1781–1788 (2003).
doi: 10.1099/vir.0.19088-0 pubmed: 12810872
Sherry, B., Mosser, A. G., Colonno, R. J. & Rueckert, R. R. Use of monoclonal antibodies to identify four neutralization immunogens on a common cold picornavirus, human rhinovirus 14. J. Virol. 57, 246–257 (1986).
doi: 10.1128/jvi.57.1.246-257.1986 pubmed: 2416951 pmcid: 252721
Huang, K. Y. A. Structural basis for neutralization of enterovirus. Curr. Opin. Virol. 51, 199–206 (2021).
doi: 10.1016/j.coviro.2021.10.006 pubmed: 34749266
Mateu, M. G. Antibody recognition of picornaviruses and escape from neutralization: a structural view. Virus Res. 38, 1–24 (1995).
doi: 10.1016/0168-1702(95)00048-U pubmed: 8546007
Cifuente, J. O. & Moratorio, G. Evolutionary and structural overview of human picornavirus capsid antibody evasion. Front. Cell Infect. Microbiol 9, 1–11 (2019).
doi: 10.3389/fcimb.2019.00283
Dotzauer, A. & Kraemer, L. Innate and adaptive immune responses against picornaviruses and their counteractions: an overview. World J. Virol. 1, 91–107 (2012).
doi: 10.5501/wjv.v1.i3.91 pubmed: 24175214 pmcid: 3782268
Doud, M. B., Hensley, S. E. & Bloom, J. D. Complete mapping of viral escape from neutralizing antibodies. PLoS Pathog. 13, 1–20 (2017).
doi: 10.1371/journal.ppat.1006271
Mattenberger, F., Latorre, V., Tirosh, O., Stern, A. & Geller, R. Globally defining the effects of mutations in a picornavirus capsid. Elife 10, 1–56 (2021).
doi: 10.7554/eLife.64256
Álvarez-Rodríguez, B., Buceta, J. & Geller, R. Comprehensive profiling of neutralizing polyclonal sera targeting coxsackievirus B3. Zenodo https://doi.org/10.5281/zenodo.8278367 . (2023)
Muckelbauer, J. K. et al. The structure of coxsackievirus B3 at 3.5 å resolution. Structure 3, 653–667 (1995).
doi: 10.1016/S0969-2126(01)00201-5 pubmed: 8591043
Fairweather, D. & Rose, N. R. Coxsackievirus-induced myocarditis in mice: a model of autoimmune disease for studying immunotoxicity. Methods 41, 118–122 (2007).
doi: 10.1016/j.ymeth.2006.07.009 pubmed: 17161308 pmcid: 1764911
Robinson, C. M., Wang, Y. & Pfeiffer, J. K. Sex-dependent intestinal replication of an enteric virus. J. Virol. 91, e02101-16 (2017).
Wang, K. et al. Serotype specific epitopes identified by neutralizing antibodies underpin immunogenic differences in Enterovirus B. Nat. Commun. 11, 1–12 (2020).
Yin, Z. et al. Atomic structures of enterovirus D68 in complex with two monoclonal antibodies define distinct mechanisms of viral neutralization. Nat. Microbiol. 4, 124–133 (2019).
Xu, L. et al. Atomic structures of Coxsackievirus A6 and its complex with a neutralizing antibody. Nat. Commun. 8, 505 (2017).
doi: 10.1038/s41467-017-00477-9 pubmed: 28894095 pmcid: 5593947
Brouwer, L., Moreni, G., Wolthers, K. C. & Pajkrt, D. World-wide prevalence and genotype distribution of enteroviruses. Viruses 13, 434 (2021).
doi: 10.3390/v13030434 pubmed: 33800518 pmcid: 7999254
Rachlin, A. et al. Progress toward polio eradication — worldwide, January 2020–April 2022. MMWR Morb. Mortal. Wkly Rep. 71, 650–655 (2022).
doi: 10.15585/mmwr.mm7119a2 pubmed: 35552352 pmcid: 9098249
Vogt, M. R. et al. Human antibodies neutralize enterovirus D68 and protect against infection and paralytic disease. Sci. Immunol. 5, eaba4902 (2020).
He, M. et al. Identification of antibodies with non-overlapping neutralization sites that target coxsackievirus A16. 27, 249–261 (2021).
Breiman, L. Random forests. Mach. Learn. 45, 5–32 (2001).
doi: 10.1023/A:1010933404324
Breiman, L., Friedman, J. H., Olshen, R. A. & Stone, C. J. Classification and regression trees. (Routledge). https://doi.org/10.1201/9781315139470 ., 2017
Christoph M. Interpretable machine learning; a guide for making black box models explainable. (Leanpub, 2020).
Huang, K. Y. A. et al. Epitope-associated and specificity-focused features of EV71-neutralizing antibody repertoires from plasmablasts of infected children. Nat. Commun. 8, 762 (2017).
Tohma, K., Ford-Siltz, L. A., Kendra, J. A. & Parra, G. I. Dynamic immunodominance hierarchy of neutralizing antibody responses to evolving GII.4 noroviruses. Cell Rep. 39, 110689 (2022).
Muñoz-Alía, M. Á., Nace, R. A., Zhang, L. & Russell, S. J. Serotypic evolution of measles virus is constrained by multiple co-dominant B cell epitopes on its surface glycoproteins. Cell Rep. Med. 2, 100225 (2021).
doi: 10.1016/j.xcrm.2021.100225 pubmed: 33948566 pmcid: 8080110
Bouche, F. B., Ertl, O. T. & Muller, C. P. Neutralizing B cell response in measles. Viral Immunol. 15, 451–471 (2002).
doi: 10.1089/088282402760312331 pubmed: 12479395
Lindesmith, L. C. et al. Antigenic site immunodominance redirection following repeat variant exposure. Viruses 14, 1293 (2022).
Rosenfeld, A. B. et al. Cross-reactive antibody responses against nonpoliovirus enteroviruses. https://journals.asm.org/journal/mbio (2022).
Arthur Huang, K.-Y. et al. Epitope-associated and specificity-focused features of EV71-neutralizing antibody repertoires from plasmablasts of infected children. Nat. Commun. 8, 762 (2017).
doi: 10.1038/s41467-017-00736-9 pubmed: 28970483 pmcid: 5624920
Antanasijevic, A., Schulze, A. J., Reddy, V. S. & Ward, A. B. High-resolution structural analysis of enterovirus-reactive polyclonal antibodies in complex with whole virions. PNAS Nexus 1, pgac253 (2022).
Wang, K. et al. Serotype specific epitopes identified by neutralizing antibodies underpin immunogenic differences in Enterovirus B. Nat. Commun. 11, 4419 (2020).
doi: 10.1038/s41467-020-18250-w pubmed: 32887892 pmcid: 7474084
Yu, T. C. et al. A biophysical model of viral escape from polyclonal antibodies. Virus Evol. 8, veac110 (2022).
Dadonaite, B. et al. A pseudovirus system enables deep mutational scanning of the full SARS-CoV-2 spike. Cell 186, 1263–1278.e20 (2023).
doi: 10.1016/j.cell.2023.02.001 pubmed: 36868218 pmcid: 9922669
Radford, C. E. et al. Mapping the neutralizing specificity of human anti-HIV serum by deep mutational scanning. Cell Host Microbe 31, 1200–1215.e9 (2023).
doi: 10.1016/j.chom.2023.05.025 pubmed: 37327779 pmcid: 10351223
Bou, J. V., Geller, R. & Sanjuán, R. Membrane-associated enteroviruses undergo intercellular transmission as pools of sibling viral genomes. Cell Rep. 29, 714–723.e4 (2019).
doi: 10.1016/j.celrep.2019.09.014 pubmed: 31618638 pmcid: 6899498
Caro, V., Guillot, S., Delpeyroux, F. & Crainic, R. Molecular strategy for ‘serotyping’ of human enteroviruses. J. Gen. Virol. 82, 79–91 (2001).
doi: 10.1099/0022-1317-82-1-79 pubmed: 11125161
Bloom, J. D. Software for the analysis and visualization of deep mutational scanning data. BMC Bioinformatics 16, 168 (2015).
doi: 10.1186/s12859-015-0590-4 pubmed: 25990960 pmcid: 4491876
Hilton, S. et al. dms-view: interactive visualization tool for deep mutational scanning data. J. Open Source Softw. 5, 2353 (2020).
doi: 10.21105/joss.02353 pubmed: 34189395 pmcid: 8237788
Team, R. C. R: a language and environment for statistical computing. Available at https://www.R-project.org (2021).
Lilkova, E. The PyMOL Molecular Graphics System, Version 2.0, Schrodinger, LLC (2015).
Inkscape. Inkscape Project. Available at https://inkscape.org . (2020).
Xiao, C. & Rossmann, M. G. Interpretation of electron density with stereographic roadmap projections. J. Struct. Biol. 158, 182–187 (2007).
doi: 10.1016/j.jsb.2006.10.013 pubmed: 17116403
Schymkowitz, J. et al. The FoldX web server: an online force field. Nucleic Acids Res. 33, W382–W388 (2005).
doi: 10.1093/nar/gki387 pubmed: 15980494 pmcid: 1160148
Mihel, J., Šikić, M., Tomić, S., Jeren, B. & Vlahoviček, K. PSAIA – protein structure and interaction analyzer. BMC Struct. Biol. 8, 21 (2008).
doi: 10.1186/1472-6807-8-21 pubmed: 18400099 pmcid: 2364630
Erdős, G., Pajkos, M. & Dosztányi, Z. IUPred3: prediction of protein disorder enhanced with unambiguous experimental annotation and visualization of evolutionary conservation. Nucleic Acids Res. 49, W297–W303 (2021).
doi: 10.1093/nar/gkab408 pubmed: 34048569 pmcid: 8262696
Hecht, M., Bromberg, Y. & Rost, B. Better prediction of functional effects for sequence variants. BMC Genomics 16, S1 (2015).
doi: 10.1186/1471-2164-16-S8-S1 pubmed: 26110438 pmcid: 4480835
Wolfram Research, Inc. Mathematica, Version 13.0, Champaign, IL. Available at https://www.wolfram.com/mathematica . (2022).

Auteurs

Beatriz Álvarez-Rodríguez (B)

Institute for Integrative Systems Biology (I2SysBio), Universitat de Valencia-CSIC, Valencia, 46980, Spain. beatriz.alvarez-rodriguez@uv.es.

Javier Buceta (J)

Institute for Integrative Systems Biology (I2SysBio), Universitat de Valencia-CSIC, Valencia, 46980, Spain. javier.buceta@csic.es.

Ron Geller (R)

Institute for Integrative Systems Biology (I2SysBio), Universitat de Valencia-CSIC, Valencia, 46980, Spain. ron.geller@csic.es.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female
Humans United States Aged Cross-Sectional Studies Medicare Part C
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH