Serveur d'exploration sur les pandémies grippales

Attention, ce site est en cours de développement !
Attention, site généré par des moyens informatiques à partir de corpus bruts.
Les informations ne sont donc pas validées.

Transgenic mosquitoes for controlling transmission of arboviruses

Identifieur interne : 000244 ( Hal/Checkpoint ); précédent : 000243; suivant : 000245

Transgenic mosquitoes for controlling transmission of arboviruses

Auteurs : Pei-Shi Yen [France]

Source :

RBID : Hal:tel-02415206

Descripteurs français

English descriptors

Abstract

Mosquito-borne arboviruses cause some of the world’s most devastating diseases and are responsible for recent dengue, chikungunya and Zika pandemics. The yellow-fever mosquito. Aedes aegypti, plays an important role in the transmission of all three viruses. The ineffectiveness of chemical control methods targeting Ae. aegypti makes urgent the need for novel vector-based approaches for controlling these diseases. Mosquitoes control arbovirus replication by triggering immune responses. RNAi machinery is the most significant pathway playing a role on antiviral immunity. Although the role of exogenous siRNA and piRNA pathways in mosquito antiviral immunity is increasingly better understood, there is still little knowledge regarding interactions between the mosquito cellular miRNA pathway and arboviruses. Thus further analysis of mechanisms by which miRNAs may regulate arbovirus replication in mosquitoes is pivotal. In the first part of the thesis, we carried out genomic analysis to identify Ae. aegypti miRNAs that potentially interact with various lineages and genotypes of chikungunya (CHIKV), dengue (DENV) and Zika viruses. By using prediction tools with distinct algorithms, several miRNA binding sites were commonly found within different genotypes/and or lineages of each arbovirus. We further analyzed the miRNAs that could target more than one arbovirus and required a low energy threshold to form miRNA-vRNA (viral RNA) complexes and predicted potential RNA structures using RNAhybrid software. Thus, we predicted miRNA candidates that might participate in regulating arboviral replication in Ae. aegypti. In the second part of the thesis, we developed a miRNA-based approach that results in a dual resistance phenotype in mosquitoes to dengue serotype 3 (DENV-3) and chikungunya (CHIKV) viruses for stopping arboviruses spreading within urban cycles. The target viruses are from two distinct arboviral families and the antiviral mechanism is designed to function through the endogenous miRNA pathway in infected mosquitoes. Ten artificial antiviral 4 miRNAs capable of targeting ~97% of all published strains were designed based on derived consensus sequences of CHIKV and DENV-3. The antiviral miRNA constructs were placed under control of either an Aedes PolyUbiquitin (PUb) or Carboxypeptidase A (AeCPA) gene promoter triggering respectively expression ubiquitously in the transgenic mosquitoes or more locally in the midgut epithelial cells following a blood meal. Challenge experiments using viruses added in blood meals showed subsequent reductions in viral transmission efficiency in the saliva of transgenic mosquitoes as a result of lowered infection rate and dissemination efficiency. Several components of mosquito fitness, including larval development time, larval/pupal mortality, adult lifespan, sex ratio, and male mating competitiveness, were examined: transgenic mosquitoes with the PUb promoter showed minor fitness costs at all developing stages whereas those based on AeCPA exhibited a high fitness cost. Further development of these strains with gene editing tools could make them candidates for releases in population replacement strategies for sustainable control of multiple arbovirus diseases.


Url:

Links toward previous steps (curation, corpus...)


Links to Exploration step

Hal:tel-02415206

Le document en format XML

<record>
<TEI>
<teiHeader>
<fileDesc>
<titleStmt>
<title xml:lang="en">Transgenic mosquitoes for controlling transmission of arboviruses</title>
<title xml:lang="fr">Moustiques transgéniques pour contrôler la transmission des arbovirus</title>
<author>
<name sortKey="Yen, Pei Shi" sort="Yen, Pei Shi" uniqKey="Yen P" first="Pei-Shi" last="Yen">Pei-Shi Yen</name>
<affiliation wicri:level="1">
<hal:affiliation type="laboratory" xml:id="struct-192944" status="VALID">
<orgName>Arbovirus et Insectes Vecteurs</orgName>
<desc>
<address>
<addrLine>Département Virologie, 25-28, rue du Docteur Roux, 75724 Paris cedex 15</addrLine>
<country key="FR"></country>
</address>
<ref type="url">https://research.pasteur.fr/en/team/arboviruses-and-insect-vectors/</ref>
</desc>
<listRelation>
<relation active="#struct-300027" type="direct"></relation>
</listRelation>
<tutelles>
<tutelle active="#struct-300027" type="direct">
<org type="institution" xml:id="struct-300027" status="VALID">
<idno type="IdRef">027936643</idno>
<idno type="ISNI">0000 0001 2353 6535</idno>
<orgName>Institut Pasteur [Paris]</orgName>
<date type="start">1887-06-04</date>
<desc>
<address>
<addrLine>25-28, rue du docteur Roux, 75724 Paris cedex 15</addrLine>
<country key="FR"></country>
</address>
<ref type="url">https://www.pasteur.fr</ref>
</desc>
</org>
</tutelle>
</tutelles>
</hal:affiliation>
<country>France</country>
</affiliation>
</author>
</titleStmt>
<publicationStmt>
<idno type="wicri:source">HAL</idno>
<idno type="RBID">Hal:tel-02415206</idno>
<idno type="halId">tel-02415206</idno>
<idno type="halUri">https://tel.archives-ouvertes.fr/tel-02415206</idno>
<idno type="url">https://tel.archives-ouvertes.fr/tel-02415206</idno>
<date when="2017-12-15">2017-12-15</date>
<idno type="wicri:Area/Hal/Corpus">000624</idno>
<idno type="wicri:Area/Hal/Curation">000624</idno>
<idno type="wicri:Area/Hal/Checkpoint">000244</idno>
<idno type="wicri:explorRef" wicri:stream="Hal" wicri:step="Checkpoint">000244</idno>
</publicationStmt>
<sourceDesc>
<biblStruct>
<analytic>
<title xml:lang="en">Transgenic mosquitoes for controlling transmission of arboviruses</title>
<title xml:lang="fr">Moustiques transgéniques pour contrôler la transmission des arbovirus</title>
<author>
<name sortKey="Yen, Pei Shi" sort="Yen, Pei Shi" uniqKey="Yen P" first="Pei-Shi" last="Yen">Pei-Shi Yen</name>
<affiliation wicri:level="1">
<hal:affiliation type="laboratory" xml:id="struct-192944" status="VALID">
<orgName>Arbovirus et Insectes Vecteurs</orgName>
<desc>
<address>
<addrLine>Département Virologie, 25-28, rue du Docteur Roux, 75724 Paris cedex 15</addrLine>
<country key="FR"></country>
</address>
<ref type="url">https://research.pasteur.fr/en/team/arboviruses-and-insect-vectors/</ref>
</desc>
<listRelation>
<relation active="#struct-300027" type="direct"></relation>
</listRelation>
<tutelles>
<tutelle active="#struct-300027" type="direct">
<org type="institution" xml:id="struct-300027" status="VALID">
<idno type="IdRef">027936643</idno>
<idno type="ISNI">0000 0001 2353 6535</idno>
<orgName>Institut Pasteur [Paris]</orgName>
<date type="start">1887-06-04</date>
<desc>
<address>
<addrLine>25-28, rue du docteur Roux, 75724 Paris cedex 15</addrLine>
<country key="FR"></country>
</address>
<ref type="url">https://www.pasteur.fr</ref>
</desc>
</org>
</tutelle>
</tutelles>
</hal:affiliation>
<country>France</country>
</affiliation>
</author>
</analytic>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc>
<textClass>
<keywords scheme="mix" xml:lang="en">
<term>Aedes aegypti</term>
<term>Antiviral immunity</term>
<term>Arbovirus</term>
</keywords>
<keywords scheme="mix" xml:lang="fr">
<term>Aedes aegypti</term>
<term>Arbovirus</term>
<term>Contrôle vectoriel</term>
<term>Immunité antivirale</term>
<term>MiRNA</term>
<term>Transgénèse</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front>
<div type="abstract" xml:lang="en">
<p>Mosquito-borne arboviruses cause some of the world’s most devastating diseases and are responsible for recent dengue, chikungunya and Zika pandemics. The yellow-fever mosquito. Aedes aegypti, plays an important role in the transmission of all three viruses. The ineffectiveness of chemical control methods targeting Ae. aegypti makes urgent the need for novel vector-based approaches for controlling these diseases. Mosquitoes control arbovirus replication by triggering immune responses. RNAi machinery is the most significant pathway playing a role on antiviral immunity. Although the role of exogenous siRNA and piRNA pathways in mosquito antiviral immunity is increasingly better understood, there is still little knowledge regarding interactions between the mosquito cellular miRNA pathway and arboviruses. Thus further analysis of mechanisms by which miRNAs may regulate arbovirus replication in mosquitoes is pivotal. In the first part of the thesis, we carried out genomic analysis to identify Ae. aegypti miRNAs that potentially interact with various lineages and genotypes of chikungunya (CHIKV), dengue (DENV) and Zika viruses. By using prediction tools with distinct algorithms, several miRNA binding sites were commonly found within different genotypes/and or lineages of each arbovirus. We further analyzed the miRNAs that could target more than one arbovirus and required a low energy threshold to form miRNA-vRNA (viral RNA) complexes and predicted potential RNA structures using RNAhybrid software. Thus, we predicted miRNA candidates that might participate in regulating arboviral replication in Ae. aegypti. In the second part of the thesis, we developed a miRNA-based approach that results in a dual resistance phenotype in mosquitoes to dengue serotype 3 (DENV-3) and chikungunya (CHIKV) viruses for stopping arboviruses spreading within urban cycles. The target viruses are from two distinct arboviral families and the antiviral mechanism is designed to function through the endogenous miRNA pathway in infected mosquitoes. Ten artificial antiviral 4 miRNAs capable of targeting ~97% of all published strains were designed based on derived consensus sequences of CHIKV and DENV-3. The antiviral miRNA constructs were placed under control of either an Aedes PolyUbiquitin (PUb) or Carboxypeptidase A (AeCPA) gene promoter triggering respectively expression ubiquitously in the transgenic mosquitoes or more locally in the midgut epithelial cells following a blood meal. Challenge experiments using viruses added in blood meals showed subsequent reductions in viral transmission efficiency in the saliva of transgenic mosquitoes as a result of lowered infection rate and dissemination efficiency. Several components of mosquito fitness, including larval development time, larval/pupal mortality, adult lifespan, sex ratio, and male mating competitiveness, were examined: transgenic mosquitoes with the PUb promoter showed minor fitness costs at all developing stages whereas those based on AeCPA exhibited a high fitness cost. Further development of these strains with gene editing tools could make them candidates for releases in population replacement strategies for sustainable control of multiple arbovirus diseases.</p>
</div>
</front>
</TEI>
<hal api="V3">
<titleStmt>
<title xml:lang="en">Transgenic mosquitoes for controlling transmission of arboviruses</title>
<title xml:lang="fr">Moustiques transgéniques pour contrôler la transmission des arbovirus</title>
<author role="aut">
<persName>
<forename type="first">Pei-Shi</forename>
<surname>Yen</surname>
</persName>
<idno type="halauthorid">11136928</idno>
<affiliation ref="#struct-192944"></affiliation>
</author>
<editor role="depositor">
<persName>
<forename>ABES</forename>
<surname>STAR</surname>
</persName>
<email type="md5">f5aa7f563b02bb6adbba7496989af39a</email>
<email type="domain">abes.fr</email>
</editor>
</titleStmt>
<editionStmt>
<edition n="v1" type="current">
<date type="whenSubmitted">2019-12-17 01:01:16</date>
<date type="whenModified">2020-05-29 16:02:05</date>
<date type="whenReleased">2019-12-17 01:01:17</date>
<date type="whenProduced">2017-12-15</date>
<date type="whenEndEmbargoed">2019-12-17</date>
<ref type="file" target="https://tel.archives-ouvertes.fr/tel-02415206/document">
<date notBefore="2019-12-17"></date>
</ref>
<ref type="file" subtype="author" n="1" target="https://tel.archives-ouvertes.fr/tel-02415206/file/2017PA066340.pdf">
<date notBefore="2019-12-17"></date>
</ref>
</edition>
<respStmt>
<resp>contributor</resp>
<name key="131274">
<persName>
<forename>ABES</forename>
<surname>STAR</surname>
</persName>
<email type="md5">f5aa7f563b02bb6adbba7496989af39a</email>
<email type="domain">abes.fr</email>
</name>
</respStmt>
</editionStmt>
<publicationStmt>
<distributor>CCSD</distributor>
<idno type="halId">tel-02415206</idno>
<idno type="halUri">https://tel.archives-ouvertes.fr/tel-02415206</idno>
<idno type="halBibtex">yen:tel-02415206</idno>
<idno type="halRefHtml">Virology. Université Pierre et Marie Curie - Paris VI, 2017. English. ⟨NNT : 2017PA066340⟩</idno>
<idno type="halRef">Virology. Université Pierre et Marie Curie - Paris VI, 2017. English. ⟨NNT : 2017PA066340⟩</idno>
</publicationStmt>
<seriesStmt>
<idno type="stamp" n="STAR">STAR - Dépôt national des thèses électroniques</idno>
<idno type="stamp" n="PASTEUR">Institut Pasteur</idno>
<idno type="stamp" n="THESES-UPMC" corresp="SORBONNE-UNIVERSITE">Thèses de l'Université Pierre et Marie Curie</idno>
<idno type="stamp" n="SORBONNE-UNIVERSITE">Sorbonne Université</idno>
<idno type="stamp" n="THESES-SU" corresp="SORBONNE-UNIVERSITE">Thèses de Sorbonne Université</idno>
</seriesStmt>
<notesStmt></notesStmt>
<sourceDesc>
<biblStruct>
<analytic>
<title xml:lang="en">Transgenic mosquitoes for controlling transmission of arboviruses</title>
<title xml:lang="fr">Moustiques transgéniques pour contrôler la transmission des arbovirus</title>
<author role="aut">
<persName>
<forename type="first">Pei-Shi</forename>
<surname>Yen</surname>
</persName>
<idno type="halauthorid">11136928</idno>
<affiliation ref="#struct-192944"></affiliation>
</author>
</analytic>
<monogr>
<idno type="nnt">2017PA066340</idno>
<imprint>
<date type="dateDefended">2017-12-15</date>
</imprint>
<authority type="institution">Université Pierre et Marie Curie - Paris VI</authority>
<authority type="school">École doctorale Complexité du vivant (Paris)</authority>
<authority type="supervisor">Anna-Bella Failloux</authority>
<authority type="jury">Dominique Higuet [Président]</authority>
<authority type="jury">Frédéric Simard [Rapporteur]</authority>
<authority type="jury">Stéphanie Becker [Rapporteur]</authority>
<authority type="jury">Chu-Hong Chen</authority>
<authority type="jury">Claire Valiente Moro</authority>
</monogr>
</biblStruct>
</sourceDesc>
<profileDesc>
<langUsage>
<language ident="en">English</language>
</langUsage>
<textClass>
<keywords scheme="author">
<term xml:lang="en">Antiviral immunity</term>
<term xml:lang="en">Arbovirus</term>
<term xml:lang="en">Aedes aegypti</term>
<term xml:lang="fr">Arbovirus</term>
<term xml:lang="fr">Aedes aegypti</term>
<term xml:lang="fr">Transgénèse</term>
<term xml:lang="fr">Immunité antivirale</term>
<term xml:lang="fr">MiRNA</term>
<term xml:lang="fr">Contrôle vectoriel</term>
</keywords>
<classCode scheme="halDomain" n="sdv.mp.vir">Life Sciences [q-bio]/Microbiology and Parasitology/Virology</classCode>
<classCode scheme="halTypology" n="THESE">Theses</classCode>
</textClass>
<abstract xml:lang="en">
<p>Mosquito-borne arboviruses cause some of the world’s most devastating diseases and are responsible for recent dengue, chikungunya and Zika pandemics. The yellow-fever mosquito. Aedes aegypti, plays an important role in the transmission of all three viruses. The ineffectiveness of chemical control methods targeting Ae. aegypti makes urgent the need for novel vector-based approaches for controlling these diseases. Mosquitoes control arbovirus replication by triggering immune responses. RNAi machinery is the most significant pathway playing a role on antiviral immunity. Although the role of exogenous siRNA and piRNA pathways in mosquito antiviral immunity is increasingly better understood, there is still little knowledge regarding interactions between the mosquito cellular miRNA pathway and arboviruses. Thus further analysis of mechanisms by which miRNAs may regulate arbovirus replication in mosquitoes is pivotal. In the first part of the thesis, we carried out genomic analysis to identify Ae. aegypti miRNAs that potentially interact with various lineages and genotypes of chikungunya (CHIKV), dengue (DENV) and Zika viruses. By using prediction tools with distinct algorithms, several miRNA binding sites were commonly found within different genotypes/and or lineages of each arbovirus. We further analyzed the miRNAs that could target more than one arbovirus and required a low energy threshold to form miRNA-vRNA (viral RNA) complexes and predicted potential RNA structures using RNAhybrid software. Thus, we predicted miRNA candidates that might participate in regulating arboviral replication in Ae. aegypti. In the second part of the thesis, we developed a miRNA-based approach that results in a dual resistance phenotype in mosquitoes to dengue serotype 3 (DENV-3) and chikungunya (CHIKV) viruses for stopping arboviruses spreading within urban cycles. The target viruses are from two distinct arboviral families and the antiviral mechanism is designed to function through the endogenous miRNA pathway in infected mosquitoes. Ten artificial antiviral 4 miRNAs capable of targeting ~97% of all published strains were designed based on derived consensus sequences of CHIKV and DENV-3. The antiviral miRNA constructs were placed under control of either an Aedes PolyUbiquitin (PUb) or Carboxypeptidase A (AeCPA) gene promoter triggering respectively expression ubiquitously in the transgenic mosquitoes or more locally in the midgut epithelial cells following a blood meal. Challenge experiments using viruses added in blood meals showed subsequent reductions in viral transmission efficiency in the saliva of transgenic mosquitoes as a result of lowered infection rate and dissemination efficiency. Several components of mosquito fitness, including larval development time, larval/pupal mortality, adult lifespan, sex ratio, and male mating competitiveness, were examined: transgenic mosquitoes with the PUb promoter showed minor fitness costs at all developing stages whereas those based on AeCPA exhibited a high fitness cost. Further development of these strains with gene editing tools could make them candidates for releases in population replacement strategies for sustainable control of multiple arbovirus diseases.</p>
</abstract>
<abstract xml:lang="fr">
<p>Les arbovirus (virus transmis par des arthropodes) sont à l'origine de maladies humaines telles que la dengue, le chikungunya ou encore le Zika. Le moustique Aedes aegypti, est le vecteur majeur de ces trois arbovirus. La faible efficacité des méthodes de contrôle des populations de moustiques, principalement réalisées au moyen d'insecticides chimiques ouvre un champ de développement de nouvelles approches en lutte antivectorielle. Le moustique, hôte vecteur, contrôle la réplication virale en limitant les réponses immunitaires antivirales. La machinerie RNA interférence (RNAi) est la voie jouant un rôle majeur dans l'immunité antivirale chez le moustique. Alors que le rôle des deux voies, siRNA (" small interfering RNA ") et piRNA (" piwi-interfering RNA "), est de mieux en mieux compris dans les réactions antivirales du vecteur, peu de connaissances sont disponibles à ce jour en ce qui concernent les interactions entre la voie miRNA (" micro RNA ") et les arbovirus. Ainsi, nous proposons une analyse détaillée des mécanismes par lesquels les miARN tentent de réguler la réplication virale chez le moustique. Dans la première partie de la thèse, nous avons effectué une analyse génomique pour identifier les miRNAs pouvant interagir chez Ae. aegypti avec divers lignées/génotypes des virus chikungunya (CHIKV), de dengue (DENV) et de Zika. Avec l'aide d'outils de prédiction faisant appel à divers algorithmes, plusieurs sites de liaison de miARN avec différents lignées/génotypes de chaque arbovirus ont été identifiés. Nous avons ensuite sélectionné les miARN pouvant cibler plus d'un arbovirus et nécessitant un faible seuil d'énergie lors de la formation des complexes entre l'ARNm.</p>
</abstract>
</profileDesc>
</hal>
</record>

Pour manipuler ce document sous Unix (Dilib)

EXPLOR_STEP=$WICRI_ROOT/Sante/explor/PandemieGrippaleV1/Data/Hal/Checkpoint
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000244 | SxmlIndent | more

Ou

HfdSelect -h $EXPLOR_AREA/Data/Hal/Checkpoint/biblio.hfd -nk 000244 | SxmlIndent | more

Pour mettre un lien sur cette page dans le réseau Wicri

{{Explor lien
   |wiki=    Sante
   |area=    PandemieGrippaleV1
   |flux=    Hal
   |étape=   Checkpoint
   |type=    RBID
   |clé=     Hal:tel-02415206
   |texte=   Transgenic mosquitoes for controlling transmission of arboviruses
}}

Wicri

This area was generated with Dilib version V0.6.34.
Data generation: Wed Jun 10 11:04:28 2020. Site generation: Sun Mar 28 09:10:28 2021