Genome-Wide Analysis of Serial Passage of the Infectious Bronchitis Virus Reveals Evolutionary Dynamics Underlying Attenuation and Immunogenicity

Autores
Williman, Joaquín; Tomás, Gonzalo; Vagnozzi, Ariel Eduardo; Techera, Claudia; Brambillasca, Sebastián; Pérez, Rubén; Marandino, Ana
Año de publicación
2026
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Background/Objectives: Serial passage in embryonated eggs is widely used to attenuate the infectious bronchitis virus (IBV) for vaccine production; however, the evolutionary processes underlying attenuation and immunogenicity remain incompletely understood. Here, we analyzed genome-wide viral evolution during serial passages to investigate how mutations emerge, persist, are lost, or become fixed over time and how these dynamics relate to changes in pathogenicity and immunogenicity. Methods: Deep sequencing was performed on 11 representative serial passages (P2–P79) of the UY/11/CA/18 strain, including two derivative lineages: P7 VIR (virulent) and P53 VAC (attenuated and immunogenic). Results: This study identified an early adaptive phase characterized by a limited set of mutations potentially associated with genome replication, viral RNA processing, and virion assembly, including a key change in non-structural protein 14 and variants in M and 3c (E). This phase was followed by a broader expansion of the variant spectrum across replicase genes and delayed accumulation of Spike protein variants. Most Spike changes emerged during later passages and exhibited transient dynamics, and only a subset reached a high frequency after the establishment of early replicase- and structural-associated changes. Consistent with these dynamics, P7 VIR diverged before the late accumulation of Spike variants and retained a pathogenic phenotype, whereas P53 VAC diverged after the emergence of early high-frequency variants but before the extensive late-stage Spike variation observed in P79, which was associated with reduced immunogenicity. Conclusions: These findings support a multi-step model of IBV attenuation in which progressive filtering of genome-wide variation shapes distinct evolutionary outcomes during serial passages. This evolutionary framework provides insight into the relationship between attenuation and immunogenicity and may help guide the rational design of live attenuated vaccines.
Instituto de Virología
Fil: Williman, Joaquín. Universidad de la República. Facultad de Ciencias. Instituto de Biología. Departamento de Biología Animal. Sección Genética Evolutiva; Uruguay
Fil: Tomás, Gonzalo. Universidad de la República. Facultad de Ciencias. Instituto de Biología. Departamento de Biología Animal. Sección Genética Evolutiva; Uruguay
Fil: Vagnozzi, Ariel Eduardo. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología e Innovaciones Tecnológicas; Argentina
Fil: Vagnozzi, Ariel Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Techera, Claudia. Universidad de la República. Facultad de Ciencias. Instituto de Biología. Departamento de Biología Animal. Sección Genética Evolutiva; Uruguay
Fil: Brambillasca, Sebastián. Universidad de la República. Facultad de Veterinaria. Departamento de Producción Animal y Salud de los Sistemas Productivos. Unidad Académica de Avicultura; Uruguay
Fil: Pérez, Rubén. Universidad de la República. Facultad de Ciencias. Instituto de Biología. Departamento de Biología Animal. Sección Genética Evolutiva; Uruguay
Fil: Marandino, Ana. Universidad de la República. Facultad de Ciencias. Instituto de Biología. Departamento de Biología Animal. Sección Genética Evolutiva; Uruguay
Fuente
Vaccines 14 (6) : 467. (June 2026)
Materia
Enfermedades de los Animales
Vacuna
Inmunogenética
Bronquitis Infecciosa Aviar
Virus Bronquitis Infecciosa Aviar
Animal Diseases
Vaccines
Immunogenetics
Avian Infectious Bronchitis
Avian Infectious Bronchitis Virus
Nivel de accesibilidad
acceso abierto
Condiciones de uso
http://creativecommons.org/licenses/by-nc-sa/4.0/
Repositorio
INTA Digital (INTA)
Institución
Instituto Nacional de Tecnología Agropecuaria
OAI Identificador
oai:localhost:20.500.12123/27833
Acceder
id INTADig_de3f8b6d00efbb385d6f05707f4459e7
oai_identifier_str oai:localhost:20.500.12123/27833
network_acronym_str INTADig
repository_id_str l
network_name_str INTA Digital (INTA)
spelling Genome-Wide Analysis of Serial Passage of the Infectious Bronchitis Virus Reveals Evolutionary Dynamics Underlying Attenuation and ImmunogenicityWilliman, JoaquínTomás, GonzaloVagnozzi, Ariel EduardoTechera, ClaudiaBrambillasca, SebastiánPérez, RubénMarandino, AnaEnfermedades de los AnimalesVacunaInmunogenéticaBronquitis Infecciosa AviarVirus Bronquitis Infecciosa AviarAnimal DiseasesVaccinesImmunogeneticsAvian Infectious BronchitisAvian Infectious Bronchitis VirusBackground/Objectives: Serial passage in embryonated eggs is widely used to attenuate the infectious bronchitis virus (IBV) for vaccine production; however, the evolutionary processes underlying attenuation and immunogenicity remain incompletely understood. Here, we analyzed genome-wide viral evolution during serial passages to investigate how mutations emerge, persist, are lost, or become fixed over time and how these dynamics relate to changes in pathogenicity and immunogenicity. Methods: Deep sequencing was performed on 11 representative serial passages (P2–P79) of the UY/11/CA/18 strain, including two derivative lineages: P7 VIR (virulent) and P53 VAC (attenuated and immunogenic). Results: This study identified an early adaptive phase characterized by a limited set of mutations potentially associated with genome replication, viral RNA processing, and virion assembly, including a key change in non-structural protein 14 and variants in M and 3c (E). This phase was followed by a broader expansion of the variant spectrum across replicase genes and delayed accumulation of Spike protein variants. Most Spike changes emerged during later passages and exhibited transient dynamics, and only a subset reached a high frequency after the establishment of early replicase- and structural-associated changes. Consistent with these dynamics, P7 VIR diverged before the late accumulation of Spike variants and retained a pathogenic phenotype, whereas P53 VAC diverged after the emergence of early high-frequency variants but before the extensive late-stage Spike variation observed in P79, which was associated with reduced immunogenicity. Conclusions: These findings support a multi-step model of IBV attenuation in which progressive filtering of genome-wide variation shapes distinct evolutionary outcomes during serial passages. This evolutionary framework provides insight into the relationship between attenuation and immunogenicity and may help guide the rational design of live attenuated vaccines.Instituto de VirologíaFil: Williman, Joaquín. Universidad de la República. Facultad de Ciencias. Instituto de Biología. Departamento de Biología Animal. Sección Genética Evolutiva; UruguayFil: Tomás, Gonzalo. Universidad de la República. Facultad de Ciencias. Instituto de Biología. Departamento de Biología Animal. Sección Genética Evolutiva; UruguayFil: Vagnozzi, Ariel Eduardo. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología e Innovaciones Tecnológicas; ArgentinaFil: Vagnozzi, Ariel Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Techera, Claudia. Universidad de la República. Facultad de Ciencias. Instituto de Biología. Departamento de Biología Animal. Sección Genética Evolutiva; UruguayFil: Brambillasca, Sebastián. Universidad de la República. Facultad de Veterinaria. Departamento de Producción Animal y Salud de los Sistemas Productivos. Unidad Académica de Avicultura; UruguayFil: Pérez, Rubén. Universidad de la República. Facultad de Ciencias. Instituto de Biología. Departamento de Biología Animal. Sección Genética Evolutiva; UruguayFil: Marandino, Ana. Universidad de la República. Facultad de Ciencias. Instituto de Biología. Departamento de Biología Animal. Sección Genética Evolutiva; UruguayMDPI2026-09-17T13:21:18Z2026-09-17T13:21:18Z2026-06info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfhttp://hdl.handle.net/20.500.12123/27833https://www.mdpi.com/2076-393X/14/6/4672076-393Xhttps://doi.org/10.3390/vaccines14060467Vaccines 14 (6) : 467. (June 2026)reponame:INTA Digital (INTA)instname:Instituto Nacional de Tecnología Agropecuariaenginfo:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by-nc-sa/4.0/Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)2026-09-24T11:43:50Zoai:localhost:20.500.12123/27833instacron:INTAInstitucionalhttp://repositorio.inta.gob.ar/Organismo científico-tecnológicoNo correspondehttp://repositorio.inta.gob.ar/oai/requesttripaldi.nicolas@inta.gob.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:l2026-09-24 11:43:51.555INTA Digital (INTA) - Instituto Nacional de Tecnología Agropecuariafalse
dc.title.none.fl_str_mv Genome-Wide Analysis of Serial Passage of the Infectious Bronchitis Virus Reveals Evolutionary Dynamics Underlying Attenuation and Immunogenicity
title Genome-Wide Analysis of Serial Passage of the Infectious Bronchitis Virus Reveals Evolutionary Dynamics Underlying Attenuation and Immunogenicity
spellingShingle Genome-Wide Analysis of Serial Passage of the Infectious Bronchitis Virus Reveals Evolutionary Dynamics Underlying Attenuation and Immunogenicity
Williman, Joaquín
Enfermedades de los Animales
Vacuna
Inmunogenética
Bronquitis Infecciosa Aviar
Virus Bronquitis Infecciosa Aviar
Animal Diseases
Vaccines
Immunogenetics
Avian Infectious Bronchitis
Avian Infectious Bronchitis Virus
title_short Genome-Wide Analysis of Serial Passage of the Infectious Bronchitis Virus Reveals Evolutionary Dynamics Underlying Attenuation and Immunogenicity
title_full Genome-Wide Analysis of Serial Passage of the Infectious Bronchitis Virus Reveals Evolutionary Dynamics Underlying Attenuation and Immunogenicity
title_fullStr Genome-Wide Analysis of Serial Passage of the Infectious Bronchitis Virus Reveals Evolutionary Dynamics Underlying Attenuation and Immunogenicity
title_full_unstemmed Genome-Wide Analysis of Serial Passage of the Infectious Bronchitis Virus Reveals Evolutionary Dynamics Underlying Attenuation and Immunogenicity
title_sort Genome-Wide Analysis of Serial Passage of the Infectious Bronchitis Virus Reveals Evolutionary Dynamics Underlying Attenuation and Immunogenicity
dc.creator.none.fl_str_mv Williman, Joaquín
Tomás, Gonzalo
Vagnozzi, Ariel Eduardo
Techera, Claudia
Brambillasca, Sebastián
Pérez, Rubén
Marandino, Ana
author Williman, Joaquín
author_facet Williman, Joaquín
Tomás, Gonzalo
Vagnozzi, Ariel Eduardo
Techera, Claudia
Brambillasca, Sebastián
Pérez, Rubén
Marandino, Ana
author_role author
author2 Tomás, Gonzalo
Vagnozzi, Ariel Eduardo
Techera, Claudia
Brambillasca, Sebastián
Pérez, Rubén
Marandino, Ana
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Enfermedades de los Animales
Vacuna
Inmunogenética
Bronquitis Infecciosa Aviar
Virus Bronquitis Infecciosa Aviar
Animal Diseases
Vaccines
Immunogenetics
Avian Infectious Bronchitis
Avian Infectious Bronchitis Virus
topic Enfermedades de los Animales
Vacuna
Inmunogenética
Bronquitis Infecciosa Aviar
Virus Bronquitis Infecciosa Aviar
Animal Diseases
Vaccines
Immunogenetics
Avian Infectious Bronchitis
Avian Infectious Bronchitis Virus
dc.description.none.fl_txt_mv Background/Objectives: Serial passage in embryonated eggs is widely used to attenuate the infectious bronchitis virus (IBV) for vaccine production; however, the evolutionary processes underlying attenuation and immunogenicity remain incompletely understood. Here, we analyzed genome-wide viral evolution during serial passages to investigate how mutations emerge, persist, are lost, or become fixed over time and how these dynamics relate to changes in pathogenicity and immunogenicity. Methods: Deep sequencing was performed on 11 representative serial passages (P2–P79) of the UY/11/CA/18 strain, including two derivative lineages: P7 VIR (virulent) and P53 VAC (attenuated and immunogenic). Results: This study identified an early adaptive phase characterized by a limited set of mutations potentially associated with genome replication, viral RNA processing, and virion assembly, including a key change in non-structural protein 14 and variants in M and 3c (E). This phase was followed by a broader expansion of the variant spectrum across replicase genes and delayed accumulation of Spike protein variants. Most Spike changes emerged during later passages and exhibited transient dynamics, and only a subset reached a high frequency after the establishment of early replicase- and structural-associated changes. Consistent with these dynamics, P7 VIR diverged before the late accumulation of Spike variants and retained a pathogenic phenotype, whereas P53 VAC diverged after the emergence of early high-frequency variants but before the extensive late-stage Spike variation observed in P79, which was associated with reduced immunogenicity. Conclusions: These findings support a multi-step model of IBV attenuation in which progressive filtering of genome-wide variation shapes distinct evolutionary outcomes during serial passages. This evolutionary framework provides insight into the relationship between attenuation and immunogenicity and may help guide the rational design of live attenuated vaccines.
Instituto de Virología
Fil: Williman, Joaquín. Universidad de la República. Facultad de Ciencias. Instituto de Biología. Departamento de Biología Animal. Sección Genética Evolutiva; Uruguay
Fil: Tomás, Gonzalo. Universidad de la República. Facultad de Ciencias. Instituto de Biología. Departamento de Biología Animal. Sección Genética Evolutiva; Uruguay
Fil: Vagnozzi, Ariel Eduardo. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología e Innovaciones Tecnológicas; Argentina
Fil: Vagnozzi, Ariel Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Techera, Claudia. Universidad de la República. Facultad de Ciencias. Instituto de Biología. Departamento de Biología Animal. Sección Genética Evolutiva; Uruguay
Fil: Brambillasca, Sebastián. Universidad de la República. Facultad de Veterinaria. Departamento de Producción Animal y Salud de los Sistemas Productivos. Unidad Académica de Avicultura; Uruguay
Fil: Pérez, Rubén. Universidad de la República. Facultad de Ciencias. Instituto de Biología. Departamento de Biología Animal. Sección Genética Evolutiva; Uruguay
Fil: Marandino, Ana. Universidad de la República. Facultad de Ciencias. Instituto de Biología. Departamento de Biología Animal. Sección Genética Evolutiva; Uruguay
description Background/Objectives: Serial passage in embryonated eggs is widely used to attenuate the infectious bronchitis virus (IBV) for vaccine production; however, the evolutionary processes underlying attenuation and immunogenicity remain incompletely understood. Here, we analyzed genome-wide viral evolution during serial passages to investigate how mutations emerge, persist, are lost, or become fixed over time and how these dynamics relate to changes in pathogenicity and immunogenicity. Methods: Deep sequencing was performed on 11 representative serial passages (P2–P79) of the UY/11/CA/18 strain, including two derivative lineages: P7 VIR (virulent) and P53 VAC (attenuated and immunogenic). Results: This study identified an early adaptive phase characterized by a limited set of mutations potentially associated with genome replication, viral RNA processing, and virion assembly, including a key change in non-structural protein 14 and variants in M and 3c (E). This phase was followed by a broader expansion of the variant spectrum across replicase genes and delayed accumulation of Spike protein variants. Most Spike changes emerged during later passages and exhibited transient dynamics, and only a subset reached a high frequency after the establishment of early replicase- and structural-associated changes. Consistent with these dynamics, P7 VIR diverged before the late accumulation of Spike variants and retained a pathogenic phenotype, whereas P53 VAC diverged after the emergence of early high-frequency variants but before the extensive late-stage Spike variation observed in P79, which was associated with reduced immunogenicity. Conclusions: These findings support a multi-step model of IBV attenuation in which progressive filtering of genome-wide variation shapes distinct evolutionary outcomes during serial passages. This evolutionary framework provides insight into the relationship between attenuation and immunogenicity and may help guide the rational design of live attenuated vaccines.
publishDate 2026
dc.date.none.fl_str_mv 2026-09-17T13:21:18Z
2026-09-17T13:21:18Z
2026-06
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/20.500.12123/27833
https://www.mdpi.com/2076-393X/14/6/467
2076-393X
https://doi.org/10.3390/vaccines14060467
url http://hdl.handle.net/20.500.12123/27833
https://www.mdpi.com/2076-393X/14/6/467
https://doi.org/10.3390/vaccines14060467
identifier_str_mv 2076-393X
dc.language.none.fl_str_mv eng
language eng
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-sa/4.0/
Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)
eu_rights_str_mv openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by-nc-sa/4.0/
Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv Vaccines 14 (6) : 467. (June 2026)
reponame:INTA Digital (INTA)
instname:Instituto Nacional de Tecnología Agropecuaria
reponame_str INTA Digital (INTA)
collection INTA Digital (INTA)
instname_str Instituto Nacional de Tecnología Agropecuaria
repository.name.fl_str_mv INTA Digital (INTA) - Instituto Nacional de Tecnología Agropecuaria
repository.mail.fl_str_mv tripaldi.nicolas@inta.gob.ar
_version_ 1877227358997446656
score 13.265058

Publicaciones similares