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
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/184990
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oai:ri.conicet.gov.ar:11336/184990 |
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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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1844614400104726528 |
score |
13.070432 |