Brain Invasion by Mouse Hepatitis Virus Depends on Impairment of Tight Junctions and Beta Interferon Production in Brain Microvascular Endothelial Cells.
Identifieur interne : 001359 ( Main/Merge ); précédent : 001358; suivant : 001360Brain Invasion by Mouse Hepatitis Virus Depends on Impairment of Tight Junctions and Beta Interferon Production in Brain Microvascular Endothelial Cells.
Auteurs : Christian Bleau [Canada] ; Aveline Filliol [France] ; Michel Samson [France] ; Lucie Lamontagne [Canada]Source :
- Journal of virology [ 1098-5514 ] ; 2015.
Descripteurs français
- KwdFr :
- Amorces ADN (génétique), Animaux, Barrière hémato-encéphalique (virologie), Cellules endothéliales (métabolisme), Encéphale (virologie), Femelle, Foie (virologie), Immunohistochimie, Impédance électrique, Interféron bêta (métabolisme), Jonctions serrées (virologie), Lignée cellulaire, Microvaisseaux (cytologie), Petit ARN interférent (génétique), Réaction de polymérisation en chaine en temps réel, Souris, Souris de lignée C57BL, Test ELISA, Tropisme viral (physiologie), Virulence, Virus de l'hépatite murine (pathogénicité), Virus de l'hépatite murine (physiologie).
- MESH :
- cytologie : Microvaisseaux.
- génétique : Amorces ADN, Petit ARN interférent.
- métabolisme : Cellules endothéliales, Interféron bêta.
- pathogénicité : Virus de l'hépatite murine.
- physiologie : Tropisme viral, Virus de l'hépatite murine.
- virologie : Barrière hémato-encéphalique, Encéphale, Foie, Jonctions serrées.
- Animaux, Femelle, Immunohistochimie, Impédance électrique, Lignée cellulaire, Réaction de polymérisation en chaine en temps réel, Souris, Souris de lignée C57BL, Test ELISA, Virulence.
English descriptors
- KwdEn :
- Animals, Blood-Brain Barrier (virology), Brain (virology), Cell Line, DNA Primers (genetics), Electric Impedance, Endothelial Cells (metabolism), Enzyme-Linked Immunosorbent Assay, Female, Immunohistochemistry, Interferon-beta (metabolism), Liver (virology), Mice, Mice, Inbred C57BL, Microvessels (cytology), Murine hepatitis virus (pathogenicity), Murine hepatitis virus (physiology), RNA, Small Interfering (genetics), Real-Time Polymerase Chain Reaction, Tight Junctions (virology), Viral Tropism (physiology), Virulence.
- MESH :
- chemical , genetics : DNA Primers, RNA, Small Interfering.
- cytology : Microvessels.
- metabolism : Endothelial Cells, Interferon-beta.
- pathogenicity : Murine hepatitis virus.
- physiology : Murine hepatitis virus, Viral Tropism.
- virology : Blood-Brain Barrier, Brain, Liver, Tight Junctions.
- Animals, Cell Line, Electric Impedance, Enzyme-Linked Immunosorbent Assay, Female, Immunohistochemistry, Mice, Mice, Inbred C57BL, Real-Time Polymerase Chain Reaction, Virulence.
Abstract
Coronaviruses (CoVs) have shown neuroinvasive properties in humans and animals secondary to replication in peripheral organs, but the mechanism of neuroinvasion is unknown. The major aim of our work was to evaluate the ability of CoVs to enter the central nervous system (CNS) through the blood-brain barrier (BBB). Using the highly hepatotropic mouse hepatitis virus type 3 (MHV3), its attenuated variant, 51.6-MHV3, which shows low tropism for endothelial cells, and the weakly hepatotropic MHV-A59 strain from the murine coronavirus group, we investigated the virus-induced dysfunctions of BBB in vivo and in brain microvascular endothelial cells (BMECs) in vitro. We report here a MHV strain-specific ability to cross the BBB during acute infection according to their virulence for liver. Brain invasion was observed only in MHV3-infected mice and correlated with enhanced BBB permeability associated with decreased expression of zona occludens protein 1 (ZO-1), VE-cadherin, and occludin, but not claudin-5, in the brain or in cultured BMECs. BBB breakdown in MHV3 infection was not related to production of barrier-dysregulating inflammatory cytokines or chemokines by infected BMECs but rather to a downregulation of barrier protective beta interferon (IFN-β) production. Our findings highlight the importance of IFN-β production by infected BMECs in preserving BBB function and preventing access of blood-borne infectious viruses to the brain.
Url:
DOI: 10.1128/JVI.01501-15
PubMed: 26202229
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pubmed:26202229Le document en format XML
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The major aim of our work was to evaluate the ability of CoVs to enter the central nervous system (CNS) through the blood-brain barrier (BBB). Using the highly hepatotropic mouse hepatitis virus type 3 (MHV3), its attenuated variant, 51.6-MHV3, which shows low tropism for endothelial cells, and the weakly hepatotropic MHV-A59 strain from the murine coronavirus group, we investigated the virus-induced dysfunctions of BBB in vivo and in brain microvascular endothelial cells (BMECs) in vitro. We report here a MHV strain-specific ability to cross the BBB during acute infection according to their virulence for liver. Brain invasion was observed only in MHV3-infected mice and correlated with enhanced BBB permeability associated with decreased expression of zona occludens protein 1 (ZO-1), VE-cadherin, and occludin, but not claudin-5, in the brain or in cultured BMECs. BBB breakdown in MHV3 infection was not related to production of barrier-dysregulating inflammatory cytokines or chemokines by infected BMECs but rather to a downregulation of barrier protective beta interferon (IFN-β) production. Our findings highlight the importance of IFN-β production by infected BMECs in preserving BBB function and preventing access of blood-borne infectious viruses to the brain.</div></front></TEI><double doi="10.1128/JVI.01501-15"><HAL><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">BRAIN INVASION BY MOUSE HEPATITIS VIRUS DEPENDS ON IMPAIRMENT OF TIGHT JUNCTIONS AND INTERFERON-β PRODUCTION IN BRAIN MICROVASCULAR ENDOTHELIAL CELLS</title><author><name sortKey="Bleau, Christian" sort="Bleau, Christian" uniqKey="Bleau C" first="Christian" last="Bleau">Christian Bleau</name><affiliation wicri:level="1"><hal:affiliation type="laboratory" xml:id="struct-24083" status="VALID"> <orgName>Département des Sciences Biologiques [Montréal]</orgName> <desc> <address> <addrLine>Pavillon des sciences biologiques (SB) 141 Avenue du Président-Kennedy Montréal (Québec) H2X 1Y4</addrLine> <country key="CA"></country> </address> <ref type="url">https://bio.uqam.ca/</ref> </desc> <listRelation> <relation active="#struct-360045" type="direct"></relation> </listRelation> <tutelles><tutelle active="#struct-360045" type="direct"><org type="institution" xml:id="struct-360045" status="VALID"> <orgName>Université du Québec à Montréal = University of Québec in Montréal</orgName> <orgName type="acronym">UQAM</orgName> <desc> <address> <addrLine>Université du Québec à Montréal CP 8888, succursale Centre-ville Montréal (Québec) H3C 3P8 </addrLine> <country key="CA"></country> </address> <ref type="url">http://www.uqam.ca/</ref> </desc> </org></tutelle></tutelles></hal:affiliation><country>Canada</country></affiliation></author><author><name sortKey="Filliol, Aveline" sort="Filliol, Aveline" uniqKey="Filliol A" first="Aveline" last="Filliol">Aveline Filliol</name><affiliation wicri:level="1"><hal:affiliation type="laboratory" xml:id="struct-182194" status="VALID"> <idno type="RNSR">201722263E</idno> <orgName>Institut de recherche en santé, environnement et travail</orgName> <orgName type="acronym">Irset</orgName> <desc> <address> <addrLine>263 avenue Général Leclerc 35042 Rennes Cedex</addrLine> <country key="FR"></country> </address> <ref type="url">http://www.irset.org</ref> </desc> <listRelation> <relation active="#struct-74911" type="direct"></relation> <relation active="#struct-105160" type="direct"></relation> <relation active="#struct-528860" type="indirect"></relation> <relation active="#struct-301986" type="direct"></relation> <relation name="U1085" active="#struct-303623" type="direct"></relation> <relation active="#struct-453207" type="direct"></relation> </listRelation> <tutelles><tutelle active="#struct-74911" type="direct"><org type="institution" xml:id="struct-74911" status="VALID"> <idno type="IdRef">026402920</idno> <idno type="ISNI">0000000122483363</idno> <orgName>Université d'Angers</orgName> <orgName type="acronym">UA</orgName> <date type="start">1971-10-25</date> <desc> <address> <addrLine>Université d'Angers - 40 Rue de Rennes, BP 73532 - 49035 Angers CEDEX 01</addrLine> <country key="FR"></country> </address> <ref type="url">http://www.univ-angers.fr/</ref> </desc> </org></tutelle><tutelle active="#struct-105160" type="direct"><org type="institution" xml:id="struct-105160" status="VALID"> <orgName>Université de Rennes 1</orgName> <orgName type="acronym">UR1</orgName> <desc> <address> <addrLine>2 rue du Thabor - CS 46510 - 35065 Rennes cedex</addrLine> <country key="FR"></country> </address> <ref type="url">http://www.univ-rennes1.fr/</ref> </desc> <listRelation> <relation active="#struct-528860" type="direct"></relation> </listRelation> </org></tutelle><tutelle active="#struct-528860" type="indirect"><org type="regroupinstitution" xml:id="struct-528860" status="VALID"> <orgName>Université de Rennes</orgName> <orgName type="acronym">UNIV-RENNES</orgName> <date type="start">2018-01-01</date> <desc> <address> <country key="FR"></country> </address> </desc> </org></tutelle><tutelle active="#struct-301986" type="direct"><org type="institution" xml:id="struct-301986" status="VALID"> <orgName>École des Hautes Études en Santé Publique [EHESP]</orgName> <orgName type="acronym">EHESP</orgName> <date type="start">2016-06-20</date> <desc> <address> <addrLine>15, avenue du Pr. Léon Bernard - 35043 Rennes Cedex</addrLine> <country key="FR"></country> </address> <ref type="url">http://www.ehesp.fr/</ref> </desc> </org></tutelle><tutelle name="U1085" active="#struct-303623" type="direct"><org type="institution" xml:id="struct-303623" status="VALID"> <idno type="IdRef">026388278</idno> <orgName>Institut National de la Santé et de la Recherche Médicale</orgName> <orgName type="acronym">INSERM</orgName> <desc> <address> <addrLine>101, rue de Tolbiac, 75013 Paris </addrLine> <country key="FR"></country> </address> <ref type="url">http://www.inserm.fr</ref> </desc> </org></tutelle><tutelle active="#struct-453207" type="direct"><org type="institution" xml:id="struct-453207" status="VALID"> <orgName>Structure Fédérative de Recherche en Biologie et Santé de Rennes </orgName> <orgName type="acronym"> Biosit : Biologie - Santé - Innovation Technologique </orgName> <desc> <address> <addrLine>Université Rennes 1 - Campus Santé Villejean - 2, avenue Professeur Léon Bernard 35043 Rennes cedex</addrLine> <country key="FR"></country> </address> </desc> </org></tutelle></tutelles></hal:affiliation><country>France</country><placeName><settlement type="city">Angers</settlement><region type="region" nuts="2">Pays de la Loire</region></placeName><orgName type="university">Université d'Angers</orgName><placeName><settlement type="city">Rennes</settlement><region type="region" nuts="2">Région Bretagne</region></placeName><orgName type="university">Université de Rennes 1</orgName><orgName type="institution" wicri:auto="newGroup">Université européenne de Bretagne</orgName></affiliation></author><author><name sortKey="Samson, Michel" sort="Samson, Michel" uniqKey="Samson M" first="Michel" last="Samson">Michel Samson</name><affiliation wicri:level="1"><hal:affiliation type="laboratory" xml:id="struct-182194" status="VALID"> <idno type="RNSR">201722263E</idno> <orgName>Institut de recherche en santé, environnement et travail</orgName> <orgName type="acronym">Irset</orgName> <desc> <address> <addrLine>263 avenue Général Leclerc 35042 Rennes Cedex</addrLine> <country key="FR"></country> </address> <ref type="url">http://www.irset.org</ref> </desc> <listRelation> <relation active="#struct-74911" type="direct"></relation> <relation active="#struct-105160" type="direct"></relation> <relation active="#struct-528860" type="indirect"></relation> <relation active="#struct-301986" type="direct"></relation> <relation name="U1085" active="#struct-303623" type="direct"></relation> <relation active="#struct-453207" type="direct"></relation> </listRelation> <tutelles><tutelle active="#struct-74911" type="direct"><org type="institution" xml:id="struct-74911" status="VALID"> <idno type="IdRef">026402920</idno> <idno type="ISNI">0000000122483363</idno> <orgName>Université d'Angers</orgName> <orgName type="acronym">UA</orgName> <date type="start">1971-10-25</date> <desc> <address> <addrLine>Université d'Angers - 40 Rue de Rennes, BP 73532 - 49035 Angers CEDEX 01</addrLine> <country key="FR"></country> </address> <ref type="url">http://www.univ-angers.fr/</ref> </desc> </org></tutelle><tutelle active="#struct-105160" type="direct"><org type="institution" xml:id="struct-105160" status="VALID"> <orgName>Université de Rennes 1</orgName> <orgName type="acronym">UR1</orgName> <desc> <address> <addrLine>2 rue du Thabor - CS 46510 - 35065 Rennes cedex</addrLine> <country key="FR"></country> </address> <ref type="url">http://www.univ-rennes1.fr/</ref> </desc> <listRelation> <relation active="#struct-528860" type="direct"></relation> </listRelation> </org></tutelle><tutelle active="#struct-528860" type="indirect"><org type="regroupinstitution" xml:id="struct-528860" status="VALID"> <orgName>Université de Rennes</orgName> <orgName type="acronym">UNIV-RENNES</orgName> <date type="start">2018-01-01</date> <desc> <address> <country key="FR"></country> </address> </desc> </org></tutelle><tutelle active="#struct-301986" type="direct"><org type="institution" xml:id="struct-301986" status="VALID"> <orgName>École des Hautes Études en Santé Publique [EHESP]</orgName> <orgName type="acronym">EHESP</orgName> <date type="start">2016-06-20</date> <desc> <address> <addrLine>15, avenue du Pr. Léon Bernard - 35043 Rennes Cedex</addrLine> <country key="FR"></country> </address> <ref type="url">http://www.ehesp.fr/</ref> </desc> </org></tutelle><tutelle name="U1085" active="#struct-303623" type="direct"><org type="institution" xml:id="struct-303623" status="VALID"> <idno type="IdRef">026388278</idno> <orgName>Institut National de la Santé et de la Recherche Médicale</orgName> <orgName type="acronym">INSERM</orgName> <desc> <address> <addrLine>101, rue de Tolbiac, 75013 Paris </addrLine> <country key="FR"></country> </address> <ref type="url">http://www.inserm.fr</ref> </desc> </org></tutelle><tutelle active="#struct-453207" type="direct"><org type="institution" xml:id="struct-453207" status="VALID"> <orgName>Structure Fédérative de Recherche en Biologie et Santé de Rennes </orgName> <orgName type="acronym"> Biosit : Biologie - Santé - Innovation Technologique </orgName> <desc> <address> <addrLine>Université Rennes 1 - Campus Santé Villejean - 2, avenue Professeur Léon Bernard 35043 Rennes cedex</addrLine> <country key="FR"></country> </address> </desc> </org></tutelle></tutelles></hal:affiliation><country>France</country><placeName><settlement type="city">Angers</settlement><region type="region" nuts="2">Pays de la Loire</region></placeName><orgName type="university">Université d'Angers</orgName><placeName><settlement type="city">Rennes</settlement><region type="region" nuts="2">Région Bretagne</region></placeName><orgName type="university">Université de Rennes 1</orgName><orgName type="institution" wicri:auto="newGroup">Université européenne de Bretagne</orgName></affiliation></author><author><name sortKey="Lamontagne, Lucie" sort="Lamontagne, Lucie" uniqKey="Lamontagne L" first="Lucie" last="Lamontagne">Lucie Lamontagne</name><affiliation wicri:level="1"><hal:affiliation type="laboratory" xml:id="struct-24083" status="VALID"> <orgName>Département des Sciences Biologiques [Montréal]</orgName> <desc> <address> <addrLine>Pavillon des sciences biologiques (SB) 141 Avenue du Président-Kennedy Montréal (Québec) H2X 1Y4</addrLine> <country key="CA"></country> </address> <ref type="url">https://bio.uqam.ca/</ref> </desc> <listRelation> <relation active="#struct-360045" type="direct"></relation> </listRelation> <tutelles><tutelle active="#struct-360045" type="direct"><org type="institution" xml:id="struct-360045" status="VALID"> <orgName>Université du Québec à Montréal = University of Québec in Montréal</orgName> <orgName type="acronym">UQAM</orgName> <desc> <address> <addrLine>Université du Québec à Montréal CP 8888, succursale Centre-ville Montréal (Québec) H3C 3P8 </addrLine> <country key="CA"></country> </address> <ref type="url">http://www.uqam.ca/</ref> </desc> </org></tutelle></tutelles></hal:affiliation><country>Canada</country></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">HAL</idno><idno type="RBID">Hal:hal-01187308</idno><idno type="halId">hal-01187308</idno><idno type="halUri">https://hal-univ-rennes1.archives-ouvertes.fr/hal-01187308</idno><idno type="url">https://hal-univ-rennes1.archives-ouvertes.fr/hal-01187308</idno><idno type="doi">10.1128/JVI.01501-15</idno><date when="2015">2015</date><idno type="wicri:Area/Hal/Corpus">000023</idno><idno type="wicri:Area/Hal/Curation">000023</idno><idno type="wicri:Area/Hal/Checkpoint">000088</idno><idno type="wicri:explorRef" wicri:stream="Hal" wicri:step="Checkpoint">000088</idno><idno type="wicri:doubleKey">0022-538X:2015:Bleau C:brain:invasion:by</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">BRAIN INVASION BY MOUSE HEPATITIS VIRUS DEPENDS ON IMPAIRMENT OF TIGHT JUNCTIONS AND INTERFERON-β PRODUCTION IN BRAIN MICROVASCULAR ENDOTHELIAL CELLS</title><author><name sortKey="Bleau, Christian" sort="Bleau, Christian" uniqKey="Bleau C" first="Christian" last="Bleau">Christian Bleau</name><affiliation wicri:level="1"><hal:affiliation type="laboratory" xml:id="struct-24083" status="VALID"> <orgName>Département des Sciences Biologiques [Montréal]</orgName> <desc> <address> <addrLine>Pavillon des sciences biologiques (SB) 141 Avenue du Président-Kennedy Montréal (Québec) H2X 1Y4</addrLine> <country key="CA"></country> </address> <ref type="url">https://bio.uqam.ca/</ref> </desc> <listRelation> <relation active="#struct-360045" type="direct"></relation> </listRelation> <tutelles><tutelle active="#struct-360045" type="direct"><org type="institution" xml:id="struct-360045" status="VALID"> <orgName>Université du Québec à Montréal = University of Québec in Montréal</orgName> <orgName type="acronym">UQAM</orgName> <desc> <address> <addrLine>Université du Québec à Montréal CP 8888, succursale Centre-ville Montréal (Québec) H3C 3P8 </addrLine> <country key="CA"></country> </address> <ref type="url">http://www.uqam.ca/</ref> </desc> </org></tutelle></tutelles></hal:affiliation><country>Canada</country></affiliation></author><author><name sortKey="Filliol, Aveline" sort="Filliol, Aveline" uniqKey="Filliol A" first="Aveline" last="Filliol">Aveline Filliol</name><affiliation wicri:level="1"><hal:affiliation type="laboratory" xml:id="struct-182194" status="VALID"> <idno type="RNSR">201722263E</idno> <orgName>Institut de recherche en santé, environnement et travail</orgName> <orgName type="acronym">Irset</orgName> <desc> <address> <addrLine>263 avenue Général Leclerc 35042 Rennes Cedex</addrLine> <country key="FR"></country> </address> <ref type="url">http://www.irset.org</ref> </desc> <listRelation> <relation active="#struct-74911" type="direct"></relation> <relation active="#struct-105160" type="direct"></relation> <relation active="#struct-528860" type="indirect"></relation> <relation active="#struct-301986" type="direct"></relation> <relation name="U1085" active="#struct-303623" type="direct"></relation> <relation active="#struct-453207" type="direct"></relation> </listRelation> <tutelles><tutelle active="#struct-74911" type="direct"><org type="institution" xml:id="struct-74911" status="VALID"> <idno type="IdRef">026402920</idno> <idno type="ISNI">0000000122483363</idno> <orgName>Université d'Angers</orgName> <orgName type="acronym">UA</orgName> <date type="start">1971-10-25</date> <desc> <address> <addrLine>Université d'Angers - 40 Rue de Rennes, BP 73532 - 49035 Angers CEDEX 01</addrLine> <country key="FR"></country> </address> <ref type="url">http://www.univ-angers.fr/</ref> </desc> </org></tutelle><tutelle active="#struct-105160" type="direct"><org type="institution" xml:id="struct-105160" status="VALID"> <orgName>Université de Rennes 1</orgName> <orgName type="acronym">UR1</orgName> <desc> <address> <addrLine>2 rue du Thabor - CS 46510 - 35065 Rennes cedex</addrLine> <country key="FR"></country> </address> <ref type="url">http://www.univ-rennes1.fr/</ref> </desc> <listRelation> <relation active="#struct-528860" type="direct"></relation> </listRelation> </org></tutelle><tutelle active="#struct-528860" type="indirect"><org type="regroupinstitution" xml:id="struct-528860" status="VALID"> <orgName>Université de Rennes</orgName> <orgName type="acronym">UNIV-RENNES</orgName> <date type="start">2018-01-01</date> <desc> <address> <country key="FR"></country> </address> </desc> </org></tutelle><tutelle active="#struct-301986" type="direct"><org type="institution" xml:id="struct-301986" status="VALID"> <orgName>École des Hautes Études en Santé Publique [EHESP]</orgName> <orgName type="acronym">EHESP</orgName> <date type="start">2016-06-20</date> <desc> <address> <addrLine>15, avenue du Pr. Léon Bernard - 35043 Rennes Cedex</addrLine> <country key="FR"></country> </address> <ref type="url">http://www.ehesp.fr/</ref> </desc> </org></tutelle><tutelle name="U1085" active="#struct-303623" type="direct"><org type="institution" xml:id="struct-303623" status="VALID"> <idno type="IdRef">026388278</idno> <orgName>Institut National de la Santé et de la Recherche Médicale</orgName> <orgName type="acronym">INSERM</orgName> <desc> <address> <addrLine>101, rue de Tolbiac, 75013 Paris </addrLine> <country key="FR"></country> </address> <ref type="url">http://www.inserm.fr</ref> </desc> </org></tutelle><tutelle active="#struct-453207" type="direct"><org type="institution" xml:id="struct-453207" status="VALID"> <orgName>Structure Fédérative de Recherche en Biologie et Santé de Rennes </orgName> <orgName type="acronym"> Biosit : Biologie - Santé - Innovation Technologique </orgName> <desc> <address> <addrLine>Université Rennes 1 - Campus Santé Villejean - 2, avenue Professeur Léon Bernard 35043 Rennes cedex</addrLine> <country key="FR"></country> </address> </desc> </org></tutelle></tutelles></hal:affiliation><country>France</country><placeName><settlement type="city">Angers</settlement><region type="region" nuts="2">Pays de la Loire</region></placeName><orgName type="university">Université d'Angers</orgName><placeName><settlement type="city">Rennes</settlement><region type="region" nuts="2">Région Bretagne</region></placeName><orgName type="university">Université de Rennes 1</orgName><orgName type="institution" wicri:auto="newGroup">Université européenne de Bretagne</orgName></affiliation></author><author><name sortKey="Samson, Michel" sort="Samson, Michel" uniqKey="Samson M" first="Michel" last="Samson">Michel Samson</name><affiliation wicri:level="1"><hal:affiliation type="laboratory" xml:id="struct-182194" status="VALID"> <idno type="RNSR">201722263E</idno> <orgName>Institut de recherche en santé, environnement et travail</orgName> <orgName type="acronym">Irset</orgName> <desc> <address> <addrLine>263 avenue Général Leclerc 35042 Rennes Cedex</addrLine> <country key="FR"></country> </address> <ref type="url">http://www.irset.org</ref> </desc> <listRelation> <relation active="#struct-74911" type="direct"></relation> <relation active="#struct-105160" type="direct"></relation> <relation active="#struct-528860" type="indirect"></relation> <relation active="#struct-301986" type="direct"></relation> <relation name="U1085" active="#struct-303623" type="direct"></relation> <relation active="#struct-453207" type="direct"></relation> </listRelation> <tutelles><tutelle active="#struct-74911" type="direct"><org type="institution" xml:id="struct-74911" status="VALID"> <idno type="IdRef">026402920</idno> <idno type="ISNI">0000000122483363</idno> <orgName>Université d'Angers</orgName> <orgName type="acronym">UA</orgName> <date type="start">1971-10-25</date> <desc> <address> <addrLine>Université d'Angers - 40 Rue de Rennes, BP 73532 - 49035 Angers CEDEX 01</addrLine> <country key="FR"></country> </address> <ref type="url">http://www.univ-angers.fr/</ref> </desc> </org></tutelle><tutelle active="#struct-105160" type="direct"><org type="institution" xml:id="struct-105160" status="VALID"> <orgName>Université de Rennes 1</orgName> <orgName type="acronym">UR1</orgName> <desc> <address> <addrLine>2 rue du Thabor - CS 46510 - 35065 Rennes cedex</addrLine> <country key="FR"></country> </address> <ref type="url">http://www.univ-rennes1.fr/</ref> </desc> <listRelation> <relation active="#struct-528860" type="direct"></relation> </listRelation> </org></tutelle><tutelle active="#struct-528860" type="indirect"><org type="regroupinstitution" xml:id="struct-528860" status="VALID"> <orgName>Université de Rennes</orgName> <orgName type="acronym">UNIV-RENNES</orgName> <date type="start">2018-01-01</date> <desc> <address> <country key="FR"></country> </address> </desc> </org></tutelle><tutelle active="#struct-301986" type="direct"><org type="institution" xml:id="struct-301986" status="VALID"> <orgName>École des Hautes Études en Santé Publique [EHESP]</orgName> <orgName type="acronym">EHESP</orgName> <date type="start">2016-06-20</date> <desc> <address> <addrLine>15, avenue du Pr. Léon Bernard - 35043 Rennes Cedex</addrLine> <country key="FR"></country> </address> <ref type="url">http://www.ehesp.fr/</ref> </desc> </org></tutelle><tutelle name="U1085" active="#struct-303623" type="direct"><org type="institution" xml:id="struct-303623" status="VALID"> <idno type="IdRef">026388278</idno> <orgName>Institut National de la Santé et de la Recherche Médicale</orgName> <orgName type="acronym">INSERM</orgName> <desc> <address> <addrLine>101, rue de Tolbiac, 75013 Paris </addrLine> <country key="FR"></country> </address> <ref type="url">http://www.inserm.fr</ref> </desc> </org></tutelle><tutelle active="#struct-453207" type="direct"><org type="institution" xml:id="struct-453207" status="VALID"> <orgName>Structure Fédérative de Recherche en Biologie et Santé de Rennes </orgName> <orgName type="acronym"> Biosit : Biologie - Santé - Innovation Technologique </orgName> <desc> <address> <addrLine>Université Rennes 1 - Campus Santé Villejean - 2, avenue Professeur Léon Bernard 35043 Rennes cedex</addrLine> <country key="FR"></country> </address> </desc> </org></tutelle></tutelles></hal:affiliation><country>France</country><placeName><settlement type="city">Angers</settlement><region type="region" nuts="2">Pays de la Loire</region></placeName><orgName type="university">Université d'Angers</orgName><placeName><settlement type="city">Rennes</settlement><region type="region" nuts="2">Région Bretagne</region></placeName><orgName type="university">Université de Rennes 1</orgName><orgName type="institution" wicri:auto="newGroup">Université européenne de Bretagne</orgName></affiliation></author><author><name sortKey="Lamontagne, Lucie" sort="Lamontagne, Lucie" uniqKey="Lamontagne L" first="Lucie" last="Lamontagne">Lucie Lamontagne</name><affiliation wicri:level="1"><hal:affiliation type="laboratory" xml:id="struct-24083" status="VALID"> <orgName>Département des Sciences Biologiques [Montréal]</orgName> <desc> <address> <addrLine>Pavillon des sciences biologiques (SB) 141 Avenue du Président-Kennedy Montréal (Québec) H2X 1Y4</addrLine> <country key="CA"></country> </address> <ref type="url">https://bio.uqam.ca/</ref> </desc> <listRelation> <relation active="#struct-360045" type="direct"></relation> </listRelation> <tutelles><tutelle active="#struct-360045" type="direct"><org type="institution" xml:id="struct-360045" status="VALID"> <orgName>Université du Québec à Montréal = University of Québec in Montréal</orgName> <orgName type="acronym">UQAM</orgName> <desc> <address> <addrLine>Université du Québec à Montréal CP 8888, succursale Centre-ville Montréal (Québec) H3C 3P8 </addrLine> <country key="CA"></country> </address> <ref type="url">http://www.uqam.ca/</ref> </desc> </org></tutelle></tutelles></hal:affiliation><country>Canada</country></affiliation></author></analytic><idno type="DOI">10.1128/JVI.01501-15</idno><series><title level="j">Journal of Virology</title><idno type="ISSN">0022-538X</idno><imprint><date type="datePub">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"> <p>Unlabelled - Coronaviruses (CoVs) have shown neuroinvasive properties in humans and animals secondary to replication in peripheral organs, but the mechanism of neuroinvasion is unknown. The major aim of our work was to evaluate the ability of CoVs to enter the central nervous system (CNS) through the blood-brain barrier (BBB). Using the highly hepatotropic mouse hepatitis virus type 3 (MHV3), its attenuated variant, 51.6-MHV3, which shows low tropism for endothelial cells, and the weakly hepatotropic MHV-A59 strain from the murine coronavirus group, we investigated the virus-induced dysfunctions of BBB in vivo and in brain microvascular endothelial cells (BMECs) in vitro. We report here a MHV strain-specific ability to cross the BBB during acute infection according to their virulence for liver. Brain invasion was observed only in MHV3-infected mice and correlated with enhanced BBB permeability associated with decreased expression of zona occludens protein 1 (ZO-1), VE-cadherin, and occludin, but not claudin-5, in the brain or in cultured BMECs. BBB breakdown in MHV3 infection was not related to production of barrier-dysregulating inflammatory cytokines or chemokines by infected BMECs but rather to a downregulation of barrier protective beta interferon (IFN-β) production. Our findings highlight the importance of IFN-β production by infected BMECs in preserving BBB function and preventing access of blood-borne infectious viruses to the brain. Importance - Coronaviruses (CoVs) infect several mammals, including humans, and are associated with respiratory, gastrointestinal, and/or neurological diseases. There is some evidence that suggest that human respiratory CoVs may show neuroinvasive properties. Indeed, the severe acute respiratory syndrome coronavirus (SARS-CoV), causing severe acute respiratory syndrome, and the CoVs OC43 and 229E were found in the brains of SARS patients and multiple sclerosis patients, respectively. These findings suggest that hematogenously spread CoVs may gain access to the CNS at the BBB level. Herein we report for the first time that CoVs exhibit the ability to cross the BBB according to strain virulence. BBB invasion by CoVs correlates with virus-induced disruption of tight junctions on BMECs, leading to BBB dysfunction and enhanced permeability. We provide evidence that production of IFN-β by BMECs during CoV infection may prevent BBB breakdown and brain viral invasion.</p> </div></front></TEI></HAL><PubMed><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Brain Invasion by Mouse Hepatitis Virus Depends on Impairment of Tight Junctions and Beta Interferon Production in Brain Microvascular Endothelial Cells.</title><author><name sortKey="Bleau, Christian" sort="Bleau, Christian" uniqKey="Bleau C" first="Christian" last="Bleau">Christian Bleau</name><affiliation wicri:level="4"><nlm:affiliation>Département des Sciences Biologiques, Université du Québec à Montréal, Montréal, Québec, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Département des Sciences Biologiques, Université du Québec à Montréal, Montréal, Québec</wicri:regionArea><orgName type="university">Université du Québec à Montréal</orgName><placeName><settlement type="city">Montréal</settlement><region type="state">Québec</region></placeName></affiliation></author><author><name sortKey="Filliol, Aveline" sort="Filliol, Aveline" uniqKey="Filliol A" first="Aveline" last="Filliol">Aveline Filliol</name><affiliation wicri:level="4"><nlm:affiliation>Institut de Recherche en Santé-Environnement-Travail, Université de Rennes 1, Rennes, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Institut de Recherche en Santé-Environnement-Travail, Université de Rennes 1, Rennes</wicri:regionArea><placeName><region type="region">Région Bretagne</region><region type="old region">Région Bretagne</region><settlement type="city">Rennes</settlement></placeName><orgName type="university">Université de Rennes 1</orgName></affiliation></author><author><name sortKey="Samson, Michel" sort="Samson, Michel" uniqKey="Samson M" first="Michel" last="Samson">Michel Samson</name><affiliation wicri:level="4"><nlm:affiliation>Institut de Recherche en Santé-Environnement-Travail, Université de Rennes 1, Rennes, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Institut de Recherche en Santé-Environnement-Travail, Université de Rennes 1, Rennes</wicri:regionArea><placeName><region type="region">Région Bretagne</region><region type="old region">Région Bretagne</region><settlement type="city">Rennes</settlement></placeName><orgName type="university">Université de Rennes 1</orgName></affiliation></author><author><name sortKey="Lamontagne, Lucie" sort="Lamontagne, Lucie" uniqKey="Lamontagne L" first="Lucie" last="Lamontagne">Lucie Lamontagne</name><affiliation wicri:level="4"><nlm:affiliation>Département des Sciences Biologiques, Université du Québec à Montréal, Montréal, Québec, Canada lamontagne.lucie@uqam.ca.</nlm:affiliation><country wicri:rule="url">Canada</country><wicri:regionArea>Département des Sciences Biologiques, Université du Québec à Montréal, Montréal, Québec</wicri:regionArea><orgName type="university">Université du Québec à Montréal</orgName><placeName><settlement type="city">Montréal</settlement><region type="state">Québec</region></placeName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2015">2015</date><idno type="RBID">pubmed:26202229</idno><idno type="pmid">26202229</idno><idno type="doi">10.1128/JVI.01501-15</idno><idno type="wicri:Area/PubMed/Corpus">000D94</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000D94</idno><idno type="wicri:Area/PubMed/Curation">000D94</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">000D94</idno><idno type="wicri:Area/PubMed/Checkpoint">000E51</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">000E51</idno><idno type="wicri:Area/Ncbi/Merge">002B02</idno><idno type="wicri:Area/Ncbi/Curation">002B02</idno><idno type="wicri:Area/Ncbi/Checkpoint">002B02</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Brain Invasion by Mouse Hepatitis Virus Depends on Impairment of Tight Junctions and Beta Interferon Production in Brain Microvascular Endothelial Cells.</title><author><name sortKey="Bleau, Christian" sort="Bleau, Christian" uniqKey="Bleau C" first="Christian" last="Bleau">Christian Bleau</name><affiliation wicri:level="4"><nlm:affiliation>Département des Sciences Biologiques, Université du Québec à Montréal, Montréal, Québec, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Département des Sciences Biologiques, Université du Québec à Montréal, Montréal, Québec</wicri:regionArea><orgName type="university">Université du Québec à Montréal</orgName><placeName><settlement type="city">Montréal</settlement><region type="state">Québec</region></placeName></affiliation></author><author><name sortKey="Filliol, Aveline" sort="Filliol, Aveline" uniqKey="Filliol A" first="Aveline" last="Filliol">Aveline Filliol</name><affiliation wicri:level="4"><nlm:affiliation>Institut de Recherche en Santé-Environnement-Travail, Université de Rennes 1, Rennes, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Institut de Recherche en Santé-Environnement-Travail, Université de Rennes 1, Rennes</wicri:regionArea><placeName><region type="region">Région Bretagne</region><region type="old region">Région Bretagne</region><settlement type="city">Rennes</settlement></placeName><orgName type="university">Université de Rennes 1</orgName></affiliation></author><author><name sortKey="Samson, Michel" sort="Samson, Michel" uniqKey="Samson M" first="Michel" last="Samson">Michel Samson</name><affiliation wicri:level="4"><nlm:affiliation>Institut de Recherche en Santé-Environnement-Travail, Université de Rennes 1, Rennes, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Institut de Recherche en Santé-Environnement-Travail, Université de Rennes 1, Rennes</wicri:regionArea><placeName><region type="region">Région Bretagne</region><region type="old region">Région Bretagne</region><settlement type="city">Rennes</settlement></placeName><orgName type="university">Université de Rennes 1</orgName></affiliation></author><author><name sortKey="Lamontagne, Lucie" sort="Lamontagne, Lucie" uniqKey="Lamontagne L" first="Lucie" last="Lamontagne">Lucie Lamontagne</name><affiliation wicri:level="4"><nlm:affiliation>Département des Sciences Biologiques, Université du Québec à Montréal, Montréal, Québec, Canada lamontagne.lucie@uqam.ca.</nlm:affiliation><country wicri:rule="url">Canada</country><wicri:regionArea>Département des Sciences Biologiques, Université du Québec à Montréal, Montréal, Québec</wicri:regionArea><orgName type="university">Université du Québec à Montréal</orgName><placeName><settlement type="city">Montréal</settlement><region type="state">Québec</region></placeName></affiliation></author></analytic><series><title level="j">Journal of virology</title><idno type="eISSN">1098-5514</idno><imprint><date when="2015" type="published">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Blood-Brain Barrier (virology)</term><term>Brain (virology)</term><term>Cell Line</term><term>DNA Primers (genetics)</term><term>Electric Impedance</term><term>Endothelial Cells (metabolism)</term><term>Enzyme-Linked Immunosorbent Assay</term><term>Female</term><term>Immunohistochemistry</term><term>Interferon-beta (metabolism)</term><term>Liver (virology)</term><term>Mice</term><term>Mice, Inbred C57BL</term><term>Microvessels (cytology)</term><term>Murine hepatitis virus (pathogenicity)</term><term>Murine hepatitis virus (physiology)</term><term>RNA, Small Interfering (genetics)</term><term>Real-Time Polymerase Chain Reaction</term><term>Tight Junctions (virology)</term><term>Viral Tropism (physiology)</term><term>Virulence</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Amorces ADN (génétique)</term><term>Animaux</term><term>Barrière hémato-encéphalique (virologie)</term><term>Cellules endothéliales (métabolisme)</term><term>Encéphale (virologie)</term><term>Femelle</term><term>Foie (virologie)</term><term>Immunohistochimie</term><term>Impédance électrique</term><term>Interféron bêta (métabolisme)</term><term>Jonctions serrées (virologie)</term><term>Lignée cellulaire</term><term>Microvaisseaux (cytologie)</term><term>Petit ARN interférent (génétique)</term><term>Réaction de polymérisation en chaine en temps réel</term><term>Souris</term><term>Souris de lignée C57BL</term><term>Test ELISA</term><term>Tropisme viral (physiologie)</term><term>Virulence</term><term>Virus de l'hépatite murine (pathogénicité)</term><term>Virus de l'hépatite murine (physiologie)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>DNA Primers</term><term>RNA, Small Interfering</term></keywords><keywords scheme="MESH" qualifier="cytologie" xml:lang="fr"><term>Microvaisseaux</term></keywords><keywords scheme="MESH" qualifier="cytology" xml:lang="en"><term>Microvessels</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Amorces ADN</term><term>Petit ARN interférent</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Endothelial Cells</term><term>Interferon-beta</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Cellules endothéliales</term><term>Interféron bêta</term></keywords><keywords scheme="MESH" qualifier="pathogenicity" xml:lang="en"><term>Murine hepatitis virus</term></keywords><keywords scheme="MESH" qualifier="pathogénicité" xml:lang="fr"><term>Virus de l'hépatite murine</term></keywords><keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Tropisme viral</term><term>Virus de l'hépatite murine</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Murine hepatitis virus</term><term>Viral Tropism</term></keywords><keywords scheme="MESH" qualifier="virologie" xml:lang="fr"><term>Barrière hémato-encéphalique</term><term>Encéphale</term><term>Foie</term><term>Jonctions serrées</term></keywords><keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Blood-Brain Barrier</term><term>Brain</term><term>Liver</term><term>Tight Junctions</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Cell Line</term><term>Electric Impedance</term><term>Enzyme-Linked Immunosorbent Assay</term><term>Female</term><term>Immunohistochemistry</term><term>Mice</term><term>Mice, Inbred C57BL</term><term>Real-Time Polymerase Chain Reaction</term><term>Virulence</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Femelle</term><term>Immunohistochimie</term><term>Impédance électrique</term><term>Lignée cellulaire</term><term>Réaction de polymérisation en chaine en temps réel</term><term>Souris</term><term>Souris de lignée C57BL</term><term>Test ELISA</term><term>Virulence</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Coronaviruses (CoVs) have shown neuroinvasive properties in humans and animals secondary to replication in peripheral organs, but the mechanism of neuroinvasion is unknown. The major aim of our work was to evaluate the ability of CoVs to enter the central nervous system (CNS) through the blood-brain barrier (BBB). Using the highly hepatotropic mouse hepatitis virus type 3 (MHV3), its attenuated variant, 51.6-MHV3, which shows low tropism for endothelial cells, and the weakly hepatotropic MHV-A59 strain from the murine coronavirus group, we investigated the virus-induced dysfunctions of BBB in vivo and in brain microvascular endothelial cells (BMECs) in vitro. We report here a MHV strain-specific ability to cross the BBB during acute infection according to their virulence for liver. Brain invasion was observed only in MHV3-infected mice and correlated with enhanced BBB permeability associated with decreased expression of zona occludens protein 1 (ZO-1), VE-cadherin, and occludin, but not claudin-5, in the brain or in cultured BMECs. BBB breakdown in MHV3 infection was not related to production of barrier-dysregulating inflammatory cytokines or chemokines by infected BMECs but rather to a downregulation of barrier protective beta interferon (IFN-β) production. Our findings highlight the importance of IFN-β production by infected BMECs in preserving BBB function and preventing access of blood-borne infectious viruses to the brain.</div></front></TEI></PubMed></double></record>Pour manipuler ce document sous Unix (Dilib)
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