Chikungunya virus replication rate determines the capacity of crossing tissue barriers in mosquitoes

Autores
Merwaiss, Fernando; Filomatori, Claudia Veronica; Susuki, Yasutsugu; Bardossy, Eugenia Soledad; Alvarez, Diego Ezequiel; Salehb, María Carla
Año de publicación
2021
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Chikungunya virus (CHIKV) is a reemerging and rapidly spreading pathogen transmitted by mosquitoes. The emergence of new epidemic variants of the virus is associated with genetic evolutionary traits, including duplication of repeated RNA elements in the 3= untranslated region (UTR) that seemingly favor transmission by mosquitoes. The transmission potential of a given variant results from a complex interplay between virus populations and anatomical tissue barriers in the mosquito. Here, we used the wild-type CHIKV Caribbean strain and an engineered mutant harboring a deletion in the 3= UTR to dissect the interactions of virus variants with the anatomical barriers that impede transmission during the replication cycle of the virus in Aedes mosquitoes. Compared to the 3=-UTR mutant, we observed that the wild-type virus had a short extrinsic incubation period (EIP) after an infectious blood meal and was expectorated into mosquito saliva much more efficiently. We found that high viral titers in the midgut are not sufficient to escape the midgut escape barrier. Rather, viral replication kinetics play a crucial role in determining midgut escape and the transmission ability of CHIKV. Finally, competition tests in mosquitoes coinfected with wild-type and mutant viruses revealed that both viruses successfully colonized the midgut, but wild-type viruses effectively displaced mutant viruses during systemic infection due to their greater efficiency of escaping from the midgut into secondary tissues. Overall, our results uncover a link between CHIKV replication kinetics and the effect of bottlenecks on population diversity, as slowly replicating variants are less able to overcome the midgut escape barrier. IMPORTANCE It is well established that selective pressures in mosquito vectors impose population bottlenecks for arboviruses. Here, we used a CHIKV Caribbean lineage mutant carrying a deletion in the 3= UTR to study host-virus interactions in vivo in the epidemic mosquito vector Aedes aegypti. We found that the mutant virus had a delayed replication rate in mosquitoes, which lengthened the extrinsic incubation period (EIP) and reduced fitness relative to the wild-type virus. As a result, the mutant virus displayed a reduced capacity to cross anatomical barriers during the infection cycle in mosquitoes, thus reducing the virus transmission rate. Our findings show how selective pressures act on CHIKV noncoding regions to select variants with shorter EIPs that are preferentially transmitted by the mosquito vector.
Fil: Merwaiss, Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; Argentina. Centre National de la Recherche Scientifique; Francia. Institut Pasteur de Paris.; Francia
Fil: Filomatori, Claudia Veronica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; Argentina
Fil: Susuki, Yasutsugu. Centre National de la Recherche Scientifique; Francia. Institut Pasteur de Paris.; Francia
Fil: Bardossy, Eugenia Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; Argentina
Fil: Alvarez, Diego Ezequiel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; Argentina
Fil: Salehb, María Carla. Centre National de la Recherche Scientifique; Francia. Institut Pasteur de Paris.; Francia
Materia
3= UTR
ALPHAVIRUS
ARTHROPOD VECTORS
BOTTLENECKS
EXTRINSIC INCUBATION PERIOD
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/184990

id CONICETDig_0d456c71ec8e371964ee62c7791af044
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network_acronym_str CONICETDig
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network_name_str CONICET Digital (CONICET)
spelling Chikungunya virus replication rate determines the capacity of crossing tissue barriers in mosquitoesMerwaiss, FernandoFilomatori, Claudia VeronicaSusuki, YasutsuguBardossy, Eugenia SoledadAlvarez, Diego EzequielSalehb, María Carla3= UTRALPHAVIRUSARTHROPOD VECTORSBOTTLENECKSEXTRINSIC INCUBATION PERIODhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Chikungunya virus (CHIKV) is a reemerging and rapidly spreading pathogen transmitted by mosquitoes. The emergence of new epidemic variants of the virus is associated with genetic evolutionary traits, including duplication of repeated RNA elements in the 3= untranslated region (UTR) that seemingly favor transmission by mosquitoes. The transmission potential of a given variant results from a complex interplay between virus populations and anatomical tissue barriers in the mosquito. Here, we used the wild-type CHIKV Caribbean strain and an engineered mutant harboring a deletion in the 3= UTR to dissect the interactions of virus variants with the anatomical barriers that impede transmission during the replication cycle of the virus in Aedes mosquitoes. Compared to the 3=-UTR mutant, we observed that the wild-type virus had a short extrinsic incubation period (EIP) after an infectious blood meal and was expectorated into mosquito saliva much more efficiently. We found that high viral titers in the midgut are not sufficient to escape the midgut escape barrier. Rather, viral replication kinetics play a crucial role in determining midgut escape and the transmission ability of CHIKV. Finally, competition tests in mosquitoes coinfected with wild-type and mutant viruses revealed that both viruses successfully colonized the midgut, but wild-type viruses effectively displaced mutant viruses during systemic infection due to their greater efficiency of escaping from the midgut into secondary tissues. Overall, our results uncover a link between CHIKV replication kinetics and the effect of bottlenecks on population diversity, as slowly replicating variants are less able to overcome the midgut escape barrier. IMPORTANCE It is well established that selective pressures in mosquito vectors impose population bottlenecks for arboviruses. Here, we used a CHIKV Caribbean lineage mutant carrying a deletion in the 3= UTR to study host-virus interactions in vivo in the epidemic mosquito vector Aedes aegypti. We found that the mutant virus had a delayed replication rate in mosquitoes, which lengthened the extrinsic incubation period (EIP) and reduced fitness relative to the wild-type virus. As a result, the mutant virus displayed a reduced capacity to cross anatomical barriers during the infection cycle in mosquitoes, thus reducing the virus transmission rate. Our findings show how selective pressures act on CHIKV noncoding regions to select variants with shorter EIPs that are preferentially transmitted by the mosquito vector.Fil: Merwaiss, Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; Argentina. Centre National de la Recherche Scientifique; Francia. Institut Pasteur de Paris.; FranciaFil: Filomatori, Claudia Veronica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Susuki, Yasutsugu. Centre National de la Recherche Scientifique; Francia. Institut Pasteur de Paris.; FranciaFil: Bardossy, Eugenia Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Alvarez, Diego Ezequiel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Salehb, María Carla. Centre National de la Recherche Scientifique; Francia. Institut Pasteur de Paris.; FranciaAmerican Society for Microbiology2021-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/184990Merwaiss, Fernando; Filomatori, Claudia Veronica; Susuki, Yasutsugu; Bardossy, Eugenia Soledad; Alvarez, Diego Ezequiel; et al.; Chikungunya virus replication rate determines the capacity of crossing tissue barriers in mosquitoes; American Society for Microbiology; Journal of Virology; 95; 3; 1-2021; 1-390022-538XCONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://journals.asm.org/doi/10.1128/JVI.01956-20info:eu-repo/semantics/altIdentifier/doi/10.1128/JVI.01956-20info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:37:53Zoai:ri.conicet.gov.ar:11336/184990instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 10:37:53.579CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Chikungunya virus replication rate determines the capacity of crossing tissue barriers in mosquitoes
title Chikungunya virus replication rate determines the capacity of crossing tissue barriers in mosquitoes
spellingShingle Chikungunya virus replication rate determines the capacity of crossing tissue barriers in mosquitoes
Merwaiss, Fernando
3= UTR
ALPHAVIRUS
ARTHROPOD VECTORS
BOTTLENECKS
EXTRINSIC INCUBATION PERIOD
title_short Chikungunya virus replication rate determines the capacity of crossing tissue barriers in mosquitoes
title_full Chikungunya virus replication rate determines the capacity of crossing tissue barriers in mosquitoes
title_fullStr Chikungunya virus replication rate determines the capacity of crossing tissue barriers in mosquitoes
title_full_unstemmed Chikungunya virus replication rate determines the capacity of crossing tissue barriers in mosquitoes
title_sort Chikungunya virus replication rate determines the capacity of crossing tissue barriers in mosquitoes
dc.creator.none.fl_str_mv Merwaiss, Fernando
Filomatori, Claudia Veronica
Susuki, Yasutsugu
Bardossy, Eugenia Soledad
Alvarez, Diego Ezequiel
Salehb, María Carla
author Merwaiss, Fernando
author_facet Merwaiss, Fernando
Filomatori, Claudia Veronica
Susuki, Yasutsugu
Bardossy, Eugenia Soledad
Alvarez, Diego Ezequiel
Salehb, María Carla
author_role author
author2 Filomatori, Claudia Veronica
Susuki, Yasutsugu
Bardossy, Eugenia Soledad
Alvarez, Diego Ezequiel
Salehb, María Carla
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv 3= UTR
ALPHAVIRUS
ARTHROPOD VECTORS
BOTTLENECKS
EXTRINSIC INCUBATION PERIOD
topic 3= UTR
ALPHAVIRUS
ARTHROPOD VECTORS
BOTTLENECKS
EXTRINSIC INCUBATION PERIOD
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Chikungunya virus (CHIKV) is a reemerging and rapidly spreading pathogen transmitted by mosquitoes. The emergence of new epidemic variants of the virus is associated with genetic evolutionary traits, including duplication of repeated RNA elements in the 3= untranslated region (UTR) that seemingly favor transmission by mosquitoes. The transmission potential of a given variant results from a complex interplay between virus populations and anatomical tissue barriers in the mosquito. Here, we used the wild-type CHIKV Caribbean strain and an engineered mutant harboring a deletion in the 3= UTR to dissect the interactions of virus variants with the anatomical barriers that impede transmission during the replication cycle of the virus in Aedes mosquitoes. Compared to the 3=-UTR mutant, we observed that the wild-type virus had a short extrinsic incubation period (EIP) after an infectious blood meal and was expectorated into mosquito saliva much more efficiently. We found that high viral titers in the midgut are not sufficient to escape the midgut escape barrier. Rather, viral replication kinetics play a crucial role in determining midgut escape and the transmission ability of CHIKV. Finally, competition tests in mosquitoes coinfected with wild-type and mutant viruses revealed that both viruses successfully colonized the midgut, but wild-type viruses effectively displaced mutant viruses during systemic infection due to their greater efficiency of escaping from the midgut into secondary tissues. Overall, our results uncover a link between CHIKV replication kinetics and the effect of bottlenecks on population diversity, as slowly replicating variants are less able to overcome the midgut escape barrier. IMPORTANCE It is well established that selective pressures in mosquito vectors impose population bottlenecks for arboviruses. Here, we used a CHIKV Caribbean lineage mutant carrying a deletion in the 3= UTR to study host-virus interactions in vivo in the epidemic mosquito vector Aedes aegypti. We found that the mutant virus had a delayed replication rate in mosquitoes, which lengthened the extrinsic incubation period (EIP) and reduced fitness relative to the wild-type virus. As a result, the mutant virus displayed a reduced capacity to cross anatomical barriers during the infection cycle in mosquitoes, thus reducing the virus transmission rate. Our findings show how selective pressures act on CHIKV noncoding regions to select variants with shorter EIPs that are preferentially transmitted by the mosquito vector.
Fil: Merwaiss, Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; Argentina. Centre National de la Recherche Scientifique; Francia. Institut Pasteur de Paris.; Francia
Fil: Filomatori, Claudia Veronica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; Argentina
Fil: Susuki, Yasutsugu. Centre National de la Recherche Scientifique; Francia. Institut Pasteur de Paris.; Francia
Fil: Bardossy, Eugenia Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; Argentina
Fil: Alvarez, Diego Ezequiel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; Argentina
Fil: Salehb, María Carla. Centre National de la Recherche Scientifique; Francia. Institut Pasteur de Paris.; Francia
description Chikungunya virus (CHIKV) is a reemerging and rapidly spreading pathogen transmitted by mosquitoes. The emergence of new epidemic variants of the virus is associated with genetic evolutionary traits, including duplication of repeated RNA elements in the 3= untranslated region (UTR) that seemingly favor transmission by mosquitoes. The transmission potential of a given variant results from a complex interplay between virus populations and anatomical tissue barriers in the mosquito. Here, we used the wild-type CHIKV Caribbean strain and an engineered mutant harboring a deletion in the 3= UTR to dissect the interactions of virus variants with the anatomical barriers that impede transmission during the replication cycle of the virus in Aedes mosquitoes. Compared to the 3=-UTR mutant, we observed that the wild-type virus had a short extrinsic incubation period (EIP) after an infectious blood meal and was expectorated into mosquito saliva much more efficiently. We found that high viral titers in the midgut are not sufficient to escape the midgut escape barrier. Rather, viral replication kinetics play a crucial role in determining midgut escape and the transmission ability of CHIKV. Finally, competition tests in mosquitoes coinfected with wild-type and mutant viruses revealed that both viruses successfully colonized the midgut, but wild-type viruses effectively displaced mutant viruses during systemic infection due to their greater efficiency of escaping from the midgut into secondary tissues. Overall, our results uncover a link between CHIKV replication kinetics and the effect of bottlenecks on population diversity, as slowly replicating variants are less able to overcome the midgut escape barrier. IMPORTANCE It is well established that selective pressures in mosquito vectors impose population bottlenecks for arboviruses. Here, we used a CHIKV Caribbean lineage mutant carrying a deletion in the 3= UTR to study host-virus interactions in vivo in the epidemic mosquito vector Aedes aegypti. We found that the mutant virus had a delayed replication rate in mosquitoes, which lengthened the extrinsic incubation period (EIP) and reduced fitness relative to the wild-type virus. As a result, the mutant virus displayed a reduced capacity to cross anatomical barriers during the infection cycle in mosquitoes, thus reducing the virus transmission rate. Our findings show how selective pressures act on CHIKV noncoding regions to select variants with shorter EIPs that are preferentially transmitted by the mosquito vector.
publishDate 2021
dc.date.none.fl_str_mv 2021-01
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/11336/184990
Merwaiss, Fernando; Filomatori, Claudia Veronica; Susuki, Yasutsugu; Bardossy, Eugenia Soledad; Alvarez, Diego Ezequiel; et al.; Chikungunya virus replication rate determines the capacity of crossing tissue barriers in mosquitoes; American Society for Microbiology; Journal of Virology; 95; 3; 1-2021; 1-39
0022-538X
CONICET Digital
CONICET
url http://hdl.handle.net/11336/184990
identifier_str_mv Merwaiss, Fernando; Filomatori, Claudia Veronica; Susuki, Yasutsugu; Bardossy, Eugenia Soledad; Alvarez, Diego Ezequiel; et al.; Chikungunya virus replication rate determines the capacity of crossing tissue barriers in mosquitoes; American Society for Microbiology; Journal of Virology; 95; 3; 1-2021; 1-39
0022-538X
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://journals.asm.org/doi/10.1128/JVI.01956-20
info:eu-repo/semantics/altIdentifier/doi/10.1128/JVI.01956-20
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv American Society for Microbiology
publisher.none.fl_str_mv American Society for Microbiology
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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