The open reading frame 3a protein of severe acute respiratory syndrome-associated coronavirus promotes membrane rearrangement and cell death.
Identifieur interne : 002420 ( Main/Exploration ); précédent : 002419; suivant : 002421The open reading frame 3a protein of severe acute respiratory syndrome-associated coronavirus promotes membrane rearrangement and cell death.
Auteurs : Eric C. Freundt [États-Unis] ; Li Yu ; Cynthia S. Goldsmith ; Sarah Welsh ; Aaron Cheng ; Boyd Yount ; Wei Liu ; Matthew B. Frieman ; Ursula J. Buchholz ; Gavin R. Screaton ; Jennifer Lippincott-Schwartz ; Sherif R. Zaki ; Xiao-Ning Xu ; Ralph S. Baric ; Kanta Subbarao ; Michael J. LenardoSource :
- Journal of virology [ 1098-5514 ] ; 2010.
Descripteurs français
- KwdFr :
- Animaux, Appareil de Golgi (anatomopathologie), Appareil de Golgi (métabolisme), Cellules Vero (anatomopathologie), Délétion de gène, Facteur-1 de ribosylation de l'ADP (génétique), Facteur-1 de ribosylation de l'ADP (métabolisme), Humains, Interactions hôte-pathogène, Membrane cellulaire (anatomopathologie), Membrane cellulaire (virologie), Mort cellulaire, Protéines virales structurales (métabolisme), Transfection, Virus du SRAS (génétique), Virus du SRAS (métabolisme), Virus du SRAS (pathogénicité), Vésicules cytoplasmiques (métabolisme), Vésicules cytoplasmiques (virologie).
- MESH :
- anatomopathologie : Appareil de Golgi, Cellules Vero, Membrane cellulaire.
- génétique : Facteur-1 de ribosylation de l'ADP, Virus du SRAS.
- métabolisme : Appareil de Golgi, Facteur-1 de ribosylation de l'ADP, Protéines virales structurales, Virus du SRAS, Vésicules cytoplasmiques.
- pathogénicité : Virus du SRAS.
- virologie : Membrane cellulaire, Vésicules cytoplasmiques.
- Animaux, Délétion de gène, Humains, Interactions hôte-pathogène, Mort cellulaire, Transfection.
English descriptors
- KwdEn :
- ADP-Ribosylation Factor 1 (genetics), ADP-Ribosylation Factor 1 (metabolism), Animals, Cell Death, Cell Membrane (pathology), Cell Membrane (virology), Chlorocebus aethiops, Cytoplasmic Vesicles (metabolism), Cytoplasmic Vesicles (virology), Gene Deletion, Golgi Apparatus (metabolism), Golgi Apparatus (pathology), Host-Pathogen Interactions, Humans, SARS Virus (genetics), SARS Virus (metabolism), SARS Virus (pathogenicity), Transfection, Vero Cells (pathology), Viral Structural Proteins (metabolism).
- MESH :
- chemical , genetics : ADP-Ribosylation Factor 1.
- chemical , metabolism : ADP-Ribosylation Factor 1, Viral Structural Proteins.
- genetics : SARS Virus.
- metabolism : Cytoplasmic Vesicles, Golgi Apparatus, SARS Virus.
- pathogenicity : SARS Virus.
- pathology : Cell Membrane, Golgi Apparatus, Vero Cells.
- virology : Cell Membrane, Cytoplasmic Vesicles.
- Animals, Cell Death, Chlorocebus aethiops, Gene Deletion, Host-Pathogen Interactions, Humans, Transfection.
Abstract
The genome of the severe acute respiratory syndrome-associated coronavirus (SARS-CoV) contains eight open reading frames (ORFs) that encode novel proteins. These accessory proteins are dispensable for in vitro and in vivo replication and thus may be important for other aspects of virus-host interactions. We investigated the functions of the largest of the accessory proteins, the ORF 3a protein, using a 3a-deficient strain of SARS-CoV. Cell death of Vero cells after infection with SARS-CoV was reduced upon deletion of ORF 3a. Electron microscopy of infected cells revealed a role for ORF 3a in SARS-CoV induced vesicle formation, a prominent feature of cells from SARS patients. In addition, we report that ORF 3a is both necessary and sufficient for SARS-CoV-induced Golgi fragmentation and that the 3a protein accumulates and localizes to vesicles containing markers for late endosomes. Finally, overexpression of ADP-ribosylation factor 1 (Arf1), a small GTPase essential for the maintenance of the Golgi apparatus, restored Golgi morphology during infection. These results establish an important role for ORF 3a in SARS-CoV-induced cell death, Golgi fragmentation, and the accumulation of intracellular vesicles.
DOI: 10.1128/JVI.01662-09
PubMed: 19889773
Affiliations:
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Freundt</name><affiliation wicri:level="1"><nlm:affiliation>Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892</wicri:regionArea><wicri:noRegion>Maryland 20892</wicri:noRegion></affiliation></author><author><name sortKey="Yu, Li" sort="Yu, Li" uniqKey="Yu L" first="Li" last="Yu">Li Yu</name></author><author><name sortKey="Goldsmith, Cynthia S" sort="Goldsmith, Cynthia S" uniqKey="Goldsmith C" first="Cynthia S" last="Goldsmith">Cynthia S. 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Freundt</name><affiliation wicri:level="1"><nlm:affiliation>Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892</wicri:regionArea><wicri:noRegion>Maryland 20892</wicri:noRegion></affiliation></author><author><name sortKey="Yu, Li" sort="Yu, Li" uniqKey="Yu L" first="Li" last="Yu">Li Yu</name></author><author><name sortKey="Goldsmith, Cynthia S" sort="Goldsmith, Cynthia S" uniqKey="Goldsmith C" first="Cynthia S" last="Goldsmith">Cynthia S. Goldsmith</name></author><author><name sortKey="Welsh, Sarah" sort="Welsh, Sarah" uniqKey="Welsh S" first="Sarah" last="Welsh">Sarah Welsh</name></author><author><name sortKey="Cheng, Aaron" sort="Cheng, Aaron" uniqKey="Cheng A" first="Aaron" last="Cheng">Aaron Cheng</name></author><author><name sortKey="Yount, Boyd" sort="Yount, Boyd" uniqKey="Yount B" first="Boyd" last="Yount">Boyd Yount</name></author><author><name sortKey="Liu, Wei" sort="Liu, Wei" uniqKey="Liu W" first="Wei" last="Liu">Wei Liu</name></author><author><name sortKey="Frieman, Matthew B" sort="Frieman, Matthew B" uniqKey="Frieman M" first="Matthew B" last="Frieman">Matthew B. Frieman</name></author><author><name sortKey="Buchholz, Ursula J" sort="Buchholz, Ursula J" uniqKey="Buchholz U" first="Ursula J" last="Buchholz">Ursula J. Buchholz</name></author><author><name sortKey="Screaton, Gavin R" sort="Screaton, Gavin R" uniqKey="Screaton G" first="Gavin R" last="Screaton">Gavin R. Screaton</name></author><author><name sortKey="Lippincott Schwartz, Jennifer" sort="Lippincott Schwartz, Jennifer" uniqKey="Lippincott Schwartz J" first="Jennifer" last="Lippincott-Schwartz">Jennifer Lippincott-Schwartz</name></author><author><name sortKey="Zaki, Sherif R" sort="Zaki, Sherif R" uniqKey="Zaki S" first="Sherif R" last="Zaki">Sherif R. Zaki</name></author><author><name sortKey="Xu, Xiao Ning" sort="Xu, Xiao Ning" uniqKey="Xu X" first="Xiao-Ning" last="Xu">Xiao-Ning Xu</name></author><author><name sortKey="Baric, Ralph S" sort="Baric, Ralph S" uniqKey="Baric R" first="Ralph S" last="Baric">Ralph S. Baric</name></author><author><name sortKey="Subbarao, Kanta" sort="Subbarao, Kanta" uniqKey="Subbarao K" first="Kanta" last="Subbarao">Kanta Subbarao</name></author><author><name sortKey="Lenardo, Michael J" sort="Lenardo, Michael J" uniqKey="Lenardo M" first="Michael J" last="Lenardo">Michael J. Lenardo</name></author></analytic><series><title level="j">Journal of virology</title><idno type="eISSN">1098-5514</idno><imprint><date when="2010" type="published">2010</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>ADP-Ribosylation Factor 1 (genetics)</term><term>ADP-Ribosylation Factor 1 (metabolism)</term><term>Animals</term><term>Cell Death</term><term>Cell Membrane (pathology)</term><term>Cell Membrane (virology)</term><term>Chlorocebus aethiops</term><term>Cytoplasmic Vesicles (metabolism)</term><term>Cytoplasmic Vesicles (virology)</term><term>Gene Deletion</term><term>Golgi Apparatus (metabolism)</term><term>Golgi Apparatus (pathology)</term><term>Host-Pathogen Interactions</term><term>Humans</term><term>SARS Virus (genetics)</term><term>SARS Virus (metabolism)</term><term>SARS Virus (pathogenicity)</term><term>Transfection</term><term>Vero Cells (pathology)</term><term>Viral Structural Proteins (metabolism)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term><term>Appareil de Golgi (anatomopathologie)</term><term>Appareil de Golgi (métabolisme)</term><term>Cellules Vero (anatomopathologie)</term><term>Délétion de gène</term><term>Facteur-1 de ribosylation de l'ADP (génétique)</term><term>Facteur-1 de ribosylation de l'ADP (métabolisme)</term><term>Humains</term><term>Interactions hôte-pathogène</term><term>Membrane cellulaire (anatomopathologie)</term><term>Membrane cellulaire (virologie)</term><term>Mort cellulaire</term><term>Protéines virales structurales (métabolisme)</term><term>Transfection</term><term>Virus du SRAS (génétique)</term><term>Virus du SRAS (métabolisme)</term><term>Virus du SRAS (pathogénicité)</term><term>Vésicules cytoplasmiques (métabolisme)</term><term>Vésicules cytoplasmiques (virologie)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>ADP-Ribosylation Factor 1</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>ADP-Ribosylation Factor 1</term><term>Viral Structural Proteins</term></keywords><keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Appareil de Golgi</term><term>Cellules Vero</term><term>Membrane cellulaire</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>SARS Virus</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Facteur-1 de ribosylation de l'ADP</term><term>Virus du SRAS</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Cytoplasmic Vesicles</term><term>Golgi Apparatus</term><term>SARS Virus</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Appareil de Golgi</term><term>Facteur-1 de ribosylation de l'ADP</term><term>Protéines virales structurales</term><term>Virus du SRAS</term><term>Vésicules cytoplasmiques</term></keywords><keywords scheme="MESH" qualifier="pathogenicity" xml:lang="en"><term>SARS Virus</term></keywords><keywords scheme="MESH" qualifier="pathogénicité" xml:lang="fr"><term>Virus du SRAS</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Cell Membrane</term><term>Golgi Apparatus</term><term>Vero Cells</term></keywords><keywords scheme="MESH" qualifier="virologie" xml:lang="fr"><term>Membrane cellulaire</term><term>Vésicules cytoplasmiques</term></keywords><keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Cell Membrane</term><term>Cytoplasmic Vesicles</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Cell Death</term><term>Chlorocebus aethiops</term><term>Gene Deletion</term><term>Host-Pathogen Interactions</term><term>Humans</term><term>Transfection</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Délétion de gène</term><term>Humains</term><term>Interactions hôte-pathogène</term><term>Mort cellulaire</term><term>Transfection</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The genome of the severe acute respiratory syndrome-associated coronavirus (SARS-CoV) contains eight open reading frames (ORFs) that encode novel proteins. These accessory proteins are dispensable for in vitro and in vivo replication and thus may be important for other aspects of virus-host interactions. We investigated the functions of the largest of the accessory proteins, the ORF 3a protein, using a 3a-deficient strain of SARS-CoV. Cell death of Vero cells after infection with SARS-CoV was reduced upon deletion of ORF 3a. Electron microscopy of infected cells revealed a role for ORF 3a in SARS-CoV induced vesicle formation, a prominent feature of cells from SARS patients. In addition, we report that ORF 3a is both necessary and sufficient for SARS-CoV-induced Golgi fragmentation and that the 3a protein accumulates and localizes to vesicles containing markers for late endosomes. Finally, overexpression of ADP-ribosylation factor 1 (Arf1), a small GTPase essential for the maintenance of the Golgi apparatus, restored Golgi morphology during infection. These results establish an important role for ORF 3a in SARS-CoV-induced cell death, Golgi fragmentation, and the accumulation of intracellular vesicles.</div></front></TEI><affiliations><list><country><li>États-Unis</li></country></list><tree><noCountry><name sortKey="Baric, Ralph S" sort="Baric, Ralph S" uniqKey="Baric R" first="Ralph S" last="Baric">Ralph S. Baric</name><name sortKey="Buchholz, Ursula J" sort="Buchholz, Ursula J" uniqKey="Buchholz U" first="Ursula J" last="Buchholz">Ursula J. Buchholz</name><name sortKey="Cheng, Aaron" sort="Cheng, Aaron" uniqKey="Cheng A" first="Aaron" last="Cheng">Aaron Cheng</name><name sortKey="Frieman, Matthew B" sort="Frieman, Matthew B" uniqKey="Frieman M" first="Matthew B" last="Frieman">Matthew B. Frieman</name><name sortKey="Goldsmith, Cynthia S" sort="Goldsmith, Cynthia S" uniqKey="Goldsmith C" first="Cynthia S" last="Goldsmith">Cynthia S. Goldsmith</name><name sortKey="Lenardo, Michael J" sort="Lenardo, Michael J" uniqKey="Lenardo M" first="Michael J" last="Lenardo">Michael J. Lenardo</name><name sortKey="Lippincott Schwartz, Jennifer" sort="Lippincott Schwartz, Jennifer" uniqKey="Lippincott Schwartz J" first="Jennifer" last="Lippincott-Schwartz">Jennifer Lippincott-Schwartz</name><name sortKey="Liu, Wei" sort="Liu, Wei" uniqKey="Liu W" first="Wei" last="Liu">Wei Liu</name><name sortKey="Screaton, Gavin R" sort="Screaton, Gavin R" uniqKey="Screaton G" first="Gavin R" last="Screaton">Gavin R. Screaton</name><name sortKey="Subbarao, Kanta" sort="Subbarao, Kanta" uniqKey="Subbarao K" first="Kanta" last="Subbarao">Kanta Subbarao</name><name sortKey="Welsh, Sarah" sort="Welsh, Sarah" uniqKey="Welsh S" first="Sarah" last="Welsh">Sarah Welsh</name><name sortKey="Xu, Xiao Ning" sort="Xu, Xiao Ning" uniqKey="Xu X" first="Xiao-Ning" last="Xu">Xiao-Ning Xu</name><name sortKey="Yount, Boyd" sort="Yount, Boyd" uniqKey="Yount B" first="Boyd" last="Yount">Boyd Yount</name><name sortKey="Yu, Li" sort="Yu, Li" uniqKey="Yu L" first="Li" last="Yu">Li Yu</name><name sortKey="Zaki, Sherif R" sort="Zaki, Sherif R" uniqKey="Zaki S" first="Sherif R" last="Zaki">Sherif R. Zaki</name></noCountry><country name="États-Unis"><noRegion><name sortKey="Freundt, Eric C" sort="Freundt, Eric C" uniqKey="Freundt E" first="Eric C" last="Freundt">Eric C. Freundt</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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