Zika virus degrades the ω-3 fatty acid transporter Mfsd2a in brain microvascular endothelial cells and impairs lipid homeostasis
Identifieur interne : 000808 ( Pmc/Curation ); précédent : 000807; suivant : 000809Zika virus degrades the ω-3 fatty acid transporter Mfsd2a in brain microvascular endothelial cells and impairs lipid homeostasis
Auteurs : Jia Zhou [République populaire de Chine] ; Xiaojing Chi [République populaire de Chine] ; Min Cheng [République populaire de Chine] ; Xingyao Huang [République populaire de Chine] ; Xiuying Liu [République populaire de Chine] ; Jingjing Fan [République populaire de Chine] ; Hua Xu [République populaire de Chine] ; Tianli Lin [République populaire de Chine] ; Lei Shi [République populaire de Chine] ; Chengfeng Qin [République populaire de Chine] ; Wei Yang [République populaire de Chine]Source :
- Science Advances [ 2375-2548 ] ; 2019.
Abstract
Both the endothelial transporter Mfsd2a and docosahexaenoic acid uptake are disrupted in Zika virus–induced microcephaly models.
Url:
DOI: 10.1126/sciadv.aax7142
PubMed: 31681849
PubMed Central: 6810275
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id="aff1">NHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.</nlm:aff><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>NHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing</wicri:regionArea></affiliation></author><author><name sortKey="Cheng, Min" sort="Cheng, Min" uniqKey="Cheng M" first="Min" last="Cheng">Min Cheng</name><affiliation wicri:level="1"><nlm:aff id="aff1">NHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.</nlm:aff><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>NHC Key Laboratory of Systems Biology of Pathogens, Institute of 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sortKey="Xu, Hua" sort="Xu, Hua" uniqKey="Xu H" first="Hua" last="Xu">Hua Xu</name><affiliation wicri:level="1"><nlm:aff id="aff1">NHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.</nlm:aff><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>NHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing</wicri:regionArea></affiliation></author><author><name sortKey="Lin, Tianli" sort="Lin, Tianli" uniqKey="Lin T" first="Tianli" last="Lin">Tianli Lin</name><affiliation wicri:level="1"><nlm:aff id="aff1">NHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.</nlm:aff><country xml:lang="fr" 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C" first="Chengfeng" last="Qin">Chengfeng Qin</name><affiliation wicri:level="1"><nlm:aff id="aff2">State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.</nlm:aff><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing</wicri:regionArea></affiliation></author><author><name sortKey="Yang, Wei" sort="Yang, Wei" uniqKey="Yang W" first="Wei" last="Yang">Wei Yang</name><affiliation wicri:level="1"><nlm:aff id="aff1">NHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.</nlm:aff><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>NHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, 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uniqKey="Zhou J" first="Jia" last="Zhou">Jia Zhou</name><affiliation wicri:level="1"><nlm:aff id="aff1">NHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.</nlm:aff><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>NHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing</wicri:regionArea></affiliation></author><author><name sortKey="Chi, Xiaojing" sort="Chi, Xiaojing" uniqKey="Chi X" first="Xiaojing" last="Chi">Xiaojing Chi</name><affiliation wicri:level="1"><nlm:aff id="aff1">NHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.</nlm:aff><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>NHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing</wicri:regionArea></affiliation></author><author><name sortKey="Cheng, Min" sort="Cheng, Min" uniqKey="Cheng M" first="Min" last="Cheng">Min Cheng</name><affiliation wicri:level="1"><nlm:aff id="aff1">NHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.</nlm:aff><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>NHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing</wicri:regionArea></affiliation></author><author><name sortKey="Huang, Xingyao" sort="Huang, Xingyao" uniqKey="Huang X" first="Xingyao" last="Huang">Xingyao Huang</name><affiliation wicri:level="1"><nlm:aff id="aff2">State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.</nlm:aff><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing</wicri:regionArea></affiliation></author><author><name sortKey="Liu, Xiuying" sort="Liu, Xiuying" uniqKey="Liu X" first="Xiuying" last="Liu">Xiuying Liu</name><affiliation wicri:level="1"><nlm:aff id="aff1">NHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.</nlm:aff><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>NHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing</wicri:regionArea></affiliation></author><author><name sortKey="Fan, Jingjing" sort="Fan, Jingjing" uniqKey="Fan J" first="Jingjing" last="Fan">Jingjing Fan</name><affiliation wicri:level="1"><nlm:aff id="aff1">NHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.</nlm:aff><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>NHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing</wicri:regionArea></affiliation></author><author><name sortKey="Xu, Hua" sort="Xu, Hua" uniqKey="Xu H" first="Hua" last="Xu">Hua Xu</name><affiliation wicri:level="1"><nlm:aff id="aff1">NHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.</nlm:aff><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>NHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing</wicri:regionArea></affiliation></author><author><name sortKey="Lin, Tianli" sort="Lin, Tianli" uniqKey="Lin T" first="Tianli" last="Lin">Tianli Lin</name><affiliation wicri:level="1"><nlm:aff id="aff1">NHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.</nlm:aff><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>NHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing</wicri:regionArea></affiliation></author><author><name sortKey="Shi, Lei" sort="Shi, Lei" uniqKey="Shi L" first="Lei" last="Shi">Lei Shi</name><affiliation wicri:level="1"><nlm:aff id="aff3">The State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.</nlm:aff><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>The State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing</wicri:regionArea></affiliation></author><author><name sortKey="Qin, Chengfeng" sort="Qin, Chengfeng" uniqKey="Qin C" first="Chengfeng" last="Qin">Chengfeng Qin</name><affiliation wicri:level="1"><nlm:aff id="aff2">State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, 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<front><journal-meta><journal-id journal-id-type="nlm-ta">Sci Adv</journal-id><journal-id journal-id-type="iso-abbrev">Sci Adv</journal-id><journal-id journal-id-type="publisher-id">SciAdv</journal-id><journal-id journal-id-type="hwp">advances</journal-id><journal-title-group><journal-title>Science Advances</journal-title></journal-title-group><issn pub-type="epub">2375-2548</issn><publisher><publisher-name>American Association for the Advancement of Science</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">31681849</article-id><article-id pub-id-type="pmc">6810275</article-id><article-id pub-id-type="publisher-id">aax7142</article-id><article-id pub-id-type="doi">10.1126/sciadv.aax7142</article-id><article-categories><subj-group subj-group-type="article-type"><subject>Research Article</subject></subj-group><subj-group subj-group-type="heading"><subject>Research Articles</subject></subj-group><subj-group subj-group-type="legacy-article-type"><subject>SciAdv r-articles</subject></subj-group><subj-group subj-group-type="field"><subject>Microbiology</subject><subject>Virology</subject></subj-group><subj-group subj-group-type="overline"><subject>Virology</subject></subj-group></article-categories><title-group><article-title>Zika virus degrades the ω-3 fatty acid transporter Mfsd2a in brain microvascular endothelial cells and impairs lipid homeostasis</article-title></title-group><contrib-group><contrib contrib-type="author"><contrib-id contrib-id-type="orcid" authenticated="true">http://orcid.org/0000-0001-9029-7642</contrib-id><name><surname>Zhou</surname><given-names>Jia</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref><xref ref-type="author-notes" rid="afn1">*</xref></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid" authenticated="true">http://orcid.org/0000-0002-1298-0611</contrib-id><name><surname>Chi</surname><given-names>Xiaojing</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref><xref ref-type="author-notes" rid="afn1">*</xref></contrib><contrib contrib-type="author"><name><surname>Cheng</surname><given-names>Min</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid" authenticated="true">http://orcid.org/0000-0002-3917-8100</contrib-id><name><surname>Huang</surname><given-names>Xingyao</given-names></name><xref ref-type="aff" rid="aff2"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>Liu</surname><given-names>Xiuying</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Fan</surname><given-names>Jingjing</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Xu</surname><given-names>Hua</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Lin</surname><given-names>Tianli</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Shi</surname><given-names>Lei</given-names></name><xref ref-type="aff" rid="aff3"><sup>3</sup></xref></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid" authenticated="true">http://orcid.org/0000-0002-0632-2807</contrib-id><name><surname>Qin</surname><given-names>Chengfeng</given-names></name><xref ref-type="aff" rid="aff2"><sup>2</sup></xref></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid" authenticated="true">http://orcid.org/0000-0003-0162-4221</contrib-id><name><surname>Yang</surname><given-names>Wei</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref><xref rid="cor1" ref-type="corresp">†</xref></contrib><aff id="aff1"><label>1</label>NHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.</aff><aff id="aff2"><label>2</label>State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.</aff><aff id="aff3"><label>3</label>The State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.</aff></contrib-group><author-notes><fn id="afn1" fn-type="equal"><label>*</label><p>These authors contributed equally to this work.</p></fn><corresp id="cor1"><label>†</label>Corresponding author. Email: <email xlink:href="wyang@ipb.pumc.edu.cn">wyang@ipb.pumc.edu.cn</email></corresp></author-notes><pub-date pub-type="collection"><month>10</month><year>2019</year></pub-date><pub-date pub-type="epub"><day>23</day><month>10</month><year>2019</year></pub-date><volume>5</volume><issue>10</issue><elocation-id>eaax7142</elocation-id><history><date date-type="received"><day>16</day><month>4</month><year>2019</year></date><date date-type="accepted"><day>13</day><month>9</month><year>2019</year></date></history><permissions><copyright-statement>Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).</copyright-statement><copyright-year>2019</copyright-year><copyright-holder>The Authors</copyright-holder><license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by-nc/4.0/" id="p-2"><license-p>This is an open-access article distributed under the terms of the <ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by-nc/4.0/">Creative Commons Attribution-NonCommercial license</ext-link>, which permits use, distribution, and reproduction in any medium, so long as the resultant use is <bold>not</bold> for commercial advantage and provided the original work is properly cited.</license-p></license></permissions><abstract abstract-type="teaser"><p>Both the endothelial transporter Mfsd2a and docosahexaenoic acid uptake are disrupted in Zika virus–induced microcephaly models.</p></abstract><abstract><p>Zika virus (ZIKV) infection during pregnancy increases the risk of postnatal microcephaly. Neurovascular function provides a homeostatic environment for proper brain development. The major facilitator superfamily domain-containing protein 2 (Mfsd2a) is selectively expressed in human brain microvascular endothelial cells (hBMECs) and is the major transporter mediating the brain uptake of docosahexaenoic acid (DHA). We have discovered a pivotal role for Mfsd2a in the pathogenesis of ZIKV. ZIKV disrupted Mfsd2a both in cultured primary hBMECs and in the neonatal mouse brain. ZIKV envelope (E) protein specifically interacted with Mfsd2a and promoted Mfsd2a polyubiquitination for proteasome-dependent degradation. Infection with ZIKV or ectopic expression of ZIKV E impaired Mfsd2a-mediated DHA uptake. Lipidomic analysis revealed obvious differences in DHA-containing lipids after ZIKV infection. Supplementation with DHA rescued ZIKV-caused growth restriction and microcephaly. Our findings suggest endothelial Mfsd2a as an important pathogenic mediator and supplementation with DHA as a potential therapeutic option for ZIKV infection.</p></abstract><funding-group><award-group id="award485035"><funding-source><institution-wrap><institution>National Science and Technology Major Project</institution></institution-wrap></funding-source><award-id>2017ZX10304402-001-013</award-id></award-group><award-group id="award485034"><funding-source><institution-wrap><institution>National Natural Science Foundation of China grants</institution></institution-wrap></funding-source><award-id>81871667 and 81672030</award-id></award-group><award-group id="award485032"><funding-source><institution-wrap><institution>CAMS Initiative for Innovative Medicine Grant</institution></institution-wrap></funding-source><award-id>2016-I2M-3-020</award-id></award-group><award-group id="award485033"><funding-source><institution-wrap><institution>National Basic Research Program of China Grant</institution></institution-wrap></funding-source><award-id>2015CB554301</award-id></award-group></funding-group><custom-meta-group><custom-meta><meta-name>Copyeditor</meta-name><meta-value>Fritzie Benzon</meta-value></custom-meta></custom-meta-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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