Structural Basis for the Inhibition of Host Gene Expression by Porcine Epidemic Diarrhea Virus nsp1
Identifieur interne : 000C36 ( Main/Exploration ); précédent : 000C35; suivant : 000C37Structural Basis for the Inhibition of Host Gene Expression by Porcine Epidemic Diarrhea Virus nsp1
Auteurs : Zhou Shen [République populaire de Chine] ; Gang Ye [République populaire de Chine] ; Feng Deng [République populaire de Chine] ; Gang Wang [République populaire de Chine] ; Min Cui [République populaire de Chine] ; Liurong Fang [République populaire de Chine] ; Shaobo Xiao [République populaire de Chine] ; Zhen F. Fu [République populaire de Chine, États-Unis] ; Guiqing Peng [République populaire de Chine]Source :
- Journal of Virology [ 0022-538X ] ; 2018.
Descripteurs français
- KwdFr :
- Alignement de séquences, Animaux, Cellules HEK293, Coronavirus (génétique), Cristallographie aux rayons X, Humains, Infections à coronavirus (), Infections à coronavirus (virologie), Interactions hôte-pathogène (génétique), Interactions hôte-pathogène (physiologie), Lignée cellulaire, Maladies des porcs (), Maladies des porcs (virologie), Modèles moléculaires, Pliage des protéines, Protéines virales non structurales (), Protéines virales non structurales (génétique), Protéines virales non structurales (métabolisme), RNA replicase, Régulation de l'expression des gènes, Similitude de séquences, Structure tertiaire des protéines, Suidae, Séquence d'acides aminés, Vaccins atténués, Virus de la diarrhée porcine épidémique (), Virus de la diarrhée porcine épidémique (génétique), Virus de la gastroentérite transmissible (), Virus de la gastroentérite transmissible (génétique), Virus du SRAS (), Virus du SRAS (génétique).
- MESH :
- génétique : Coronavirus, Interactions hôte-pathogène, Protéines virales non structurales, Virus de la diarrhée porcine épidémique, Virus de la gastroentérite transmissible, Virus du SRAS.
- métabolisme : Protéines virales non structurales.
- physiologie : Interactions hôte-pathogène.
- virologie : Infections à coronavirus, Maladies des porcs.
- Alignement de séquences, Animaux, Cellules HEK293, Cristallographie aux rayons X, Humains, Infections à coronavirus, Lignée cellulaire, Maladies des porcs, Modèles moléculaires, Pliage des protéines, Protéines virales non structurales, RNA replicase, Régulation de l'expression des gènes, Similitude de séquences, Structure tertiaire des protéines, Suidae, Séquence d'acides aminés, Vaccins atténués, Virus de la diarrhée porcine épidémique, Virus de la gastroentérite transmissible, Virus du SRAS.
English descriptors
- KwdEn :
- Amino Acid Sequence, Animals, Cell Line, Coronavirus (genetics), Coronavirus Infections (prevention & control), Coronavirus Infections (virology), Crystallography, X-Ray, Gene Expression Regulation, HEK293 Cells, Host-Pathogen Interactions (genetics), Host-Pathogen Interactions (physiology), Humans, Models, Molecular, Porcine epidemic diarrhea virus (chemistry), Porcine epidemic diarrhea virus (genetics), Protein Folding, Protein Structure, Tertiary, RNA Replicase, SARS Virus (chemistry), SARS Virus (genetics), Sequence Alignment, Sequence Homology, Swine, Swine Diseases (prevention & control), Swine Diseases (virology), Transmissible gastroenteritis virus (chemistry), Transmissible gastroenteritis virus (genetics), Vaccines, Attenuated, Viral Nonstructural Proteins (chemistry), Viral Nonstructural Proteins (classification), Viral Nonstructural Proteins (genetics), Viral Nonstructural Proteins (metabolism).
- MESH :
- chemical , chemistry : Viral Nonstructural Proteins.
- chemical , classification : Viral Nonstructural Proteins.
- chemical , genetics : Viral Nonstructural Proteins.
- chemical , metabolism : Viral Nonstructural Proteins.
- chemical : RNA Replicase, Vaccines, Attenuated.
- chemistry : Porcine epidemic diarrhea virus, SARS Virus, Transmissible gastroenteritis virus.
- genetics : Coronavirus, Host-Pathogen Interactions, Porcine epidemic diarrhea virus, SARS Virus, Transmissible gastroenteritis virus.
- physiology : Host-Pathogen Interactions.
- prevention & control : Coronavirus Infections, Swine Diseases.
- virology : Coronavirus Infections, Swine Diseases.
- Amino Acid Sequence, Animals, Cell Line, Crystallography, X-Ray, Gene Expression Regulation, HEK293 Cells, Humans, Models, Molecular, Protein Folding, Protein Structure, Tertiary, Sequence Alignment, Sequence Homology, Swine.
Abstract
Porcine epidemic diarrhea virus (PEDV), an enteropathogenic
Url:
DOI: 10.1128/JVI.01896-17
PubMed: 29237834
PubMed Central: 5809747
Affiliations:
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Le document en format XML
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</placeName>
</affiliation>
</author>
<author><name sortKey="Peng, Guiqing" sort="Peng, Guiqing" uniqKey="Peng G" first="Guiqing" last="Peng">Guiqing Peng</name>
<affiliation wicri:level="1"><nlm:aff id="aff1">State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei</wicri:regionArea>
<wicri:noRegion>Hubei</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff2">College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei</wicri:regionArea>
<wicri:noRegion>Hubei</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff4">The Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural University, Wuhan, Hubei, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>The Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural University, Wuhan, Hubei</wicri:regionArea>
<wicri:noRegion>Hubei</wicri:noRegion>
</affiliation>
</author>
</analytic>
<series><title level="j">Journal of Virology</title>
<idno type="ISSN">0022-538X</idno>
<idno type="eISSN">1098-5514</idno>
<imprint><date when="2018">2018</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Amino Acid Sequence</term>
<term>Animals</term>
<term>Cell Line</term>
<term>Coronavirus (genetics)</term>
<term>Coronavirus Infections (prevention & control)</term>
<term>Coronavirus Infections (virology)</term>
<term>Crystallography, X-Ray</term>
<term>Gene Expression Regulation</term>
<term>HEK293 Cells</term>
<term>Host-Pathogen Interactions (genetics)</term>
<term>Host-Pathogen Interactions (physiology)</term>
<term>Humans</term>
<term>Models, Molecular</term>
<term>Porcine epidemic diarrhea virus (chemistry)</term>
<term>Porcine epidemic diarrhea virus (genetics)</term>
<term>Protein Folding</term>
<term>Protein Structure, Tertiary</term>
<term>RNA Replicase</term>
<term>SARS Virus (chemistry)</term>
<term>SARS Virus (genetics)</term>
<term>Sequence Alignment</term>
<term>Sequence Homology</term>
<term>Swine</term>
<term>Swine Diseases (prevention & control)</term>
<term>Swine Diseases (virology)</term>
<term>Transmissible gastroenteritis virus (chemistry)</term>
<term>Transmissible gastroenteritis virus (genetics)</term>
<term>Vaccines, Attenuated</term>
<term>Viral Nonstructural Proteins (chemistry)</term>
<term>Viral Nonstructural Proteins (classification)</term>
<term>Viral Nonstructural Proteins (genetics)</term>
<term>Viral Nonstructural Proteins (metabolism)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Alignement de séquences</term>
<term>Animaux</term>
<term>Cellules HEK293</term>
<term>Coronavirus (génétique)</term>
<term>Cristallographie aux rayons X</term>
<term>Humains</term>
<term>Infections à coronavirus ()</term>
<term>Infections à coronavirus (virologie)</term>
<term>Interactions hôte-pathogène (génétique)</term>
<term>Interactions hôte-pathogène (physiologie)</term>
<term>Lignée cellulaire</term>
<term>Maladies des porcs ()</term>
<term>Maladies des porcs (virologie)</term>
<term>Modèles moléculaires</term>
<term>Pliage des protéines</term>
<term>Protéines virales non structurales ()</term>
<term>Protéines virales non structurales (génétique)</term>
<term>Protéines virales non structurales (métabolisme)</term>
<term>RNA replicase</term>
<term>Régulation de l'expression des gènes</term>
<term>Similitude de séquences</term>
<term>Structure tertiaire des protéines</term>
<term>Suidae</term>
<term>Séquence d'acides aminés</term>
<term>Vaccins atténués</term>
<term>Virus de la diarrhée porcine épidémique ()</term>
<term>Virus de la diarrhée porcine épidémique (génétique)</term>
<term>Virus de la gastroentérite transmissible ()</term>
<term>Virus de la gastroentérite transmissible (génétique)</term>
<term>Virus du SRAS ()</term>
<term>Virus du SRAS (génétique)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Viral Nonstructural Proteins</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="classification" xml:lang="en"><term>Viral Nonstructural Proteins</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Viral Nonstructural Proteins</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Viral Nonstructural Proteins</term>
</keywords>
<keywords scheme="MESH" type="chemical" xml:lang="en"><term>RNA Replicase</term>
<term>Vaccines, Attenuated</term>
</keywords>
<keywords scheme="MESH" qualifier="chemistry" xml:lang="en"><term>Porcine epidemic diarrhea virus</term>
<term>SARS Virus</term>
<term>Transmissible gastroenteritis virus</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Coronavirus</term>
<term>Host-Pathogen Interactions</term>
<term>Porcine epidemic diarrhea virus</term>
<term>SARS Virus</term>
<term>Transmissible gastroenteritis virus</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Coronavirus</term>
<term>Interactions hôte-pathogène</term>
<term>Protéines virales non structurales</term>
<term>Virus de la diarrhée porcine épidémique</term>
<term>Virus de la gastroentérite transmissible</term>
<term>Virus du SRAS</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Protéines virales non structurales</term>
</keywords>
<keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Interactions hôte-pathogène</term>
</keywords>
<keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Host-Pathogen Interactions</term>
</keywords>
<keywords scheme="MESH" qualifier="prevention & control" xml:lang="en"><term>Coronavirus Infections</term>
<term>Swine Diseases</term>
</keywords>
<keywords scheme="MESH" qualifier="virologie" xml:lang="fr"><term>Infections à coronavirus</term>
<term>Maladies des porcs</term>
</keywords>
<keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Coronavirus Infections</term>
<term>Swine Diseases</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Amino Acid Sequence</term>
<term>Animals</term>
<term>Cell Line</term>
<term>Crystallography, X-Ray</term>
<term>Gene Expression Regulation</term>
<term>HEK293 Cells</term>
<term>Humans</term>
<term>Models, Molecular</term>
<term>Protein Folding</term>
<term>Protein Structure, Tertiary</term>
<term>Sequence Alignment</term>
<term>Sequence Homology</term>
<term>Swine</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Alignement de séquences</term>
<term>Animaux</term>
<term>Cellules HEK293</term>
<term>Cristallographie aux rayons X</term>
<term>Humains</term>
<term>Infections à coronavirus</term>
<term>Lignée cellulaire</term>
<term>Maladies des porcs</term>
<term>Modèles moléculaires</term>
<term>Pliage des protéines</term>
<term>Protéines virales non structurales</term>
<term>RNA replicase</term>
<term>Régulation de l'expression des gènes</term>
<term>Similitude de séquences</term>
<term>Structure tertiaire des protéines</term>
<term>Suidae</term>
<term>Séquence d'acides aminés</term>
<term>Vaccins atténués</term>
<term>Virus de la diarrhée porcine épidémique</term>
<term>Virus de la gastroentérite transmissible</term>
<term>Virus du SRAS</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><title>ABSTRACT</title>
<p>Porcine epidemic diarrhea virus (PEDV), an enteropathogenic <named-content content-type="genus-species">Alphacoronavirus</named-content>
, has caused enormous economic losses in the pork industry. Nonstructural protein 1 (nsp1) is a characteristic feature of alpha- and betacoronaviruses, which exhibits both functional conservation and mechanistic diversity in inhibiting host gene expression and antiviral responses. However, the detailed structure and molecular mechanisms underlying the <named-content content-type="genus-species">Alphacoronavirus</named-content>
nsp1 inhibition of host gene expression remain unclear. Here, we report the first full-length crystal structure of <named-content content-type="genus-species">Alphacoronavirus</named-content>
nsp1 from PEDV. The structure displays a six-stranded β-barrel fold in the middle of two α-helices. The core structure of PEDV nsp1 shows high similarity to those of severe acute respiratory syndrome coronavirus (SARS-CoV) nsp1 and transmissible gastroenteritis virus (TGEV) nsp1, despite its low degree of sequence homology. Using ribopuromycylation and <named-content content-type="genus-species">Renilla</named-content>
luciferase reporter assays, we showed that PEDV nsp1 can dramatically inhibit general host gene expression. Furthermore, three motifs (amino acids [aa] 67 to 71, 78 to 85, and 103 to 110) of PEDV nsp1 create a stable functional region for inhibiting protein synthesis, differing considerably from <named-content content-type="genus-species">Betacoronavirus</named-content>
nsp1. These results elucidate the detailed structural basis through which PEDV nsp1 inhibits host gene expression, providing insight into the development of a new attenuated vaccine with nsp1 modifications.</p>
<p><bold>IMPORTANCE</bold>
Porcine epidemic diarrhea virus (PEDV) has led to tremendous economic losses in the global swine industry. PEDV nsp1 plays a crucial role in inhibiting host gene expression, but its functional mechanism remains unclear. Here, we report the full-length structure of PEDV nsp1, the first among coronaviruses to be reported. The 1.25-Å resolution crystal structure of PEDV nsp1 shows high similarity to severe acute respiratory syndrome coronavirus (SARS-CoV) nsp1<sup>13–128</sup>
and transmissible gastroenteritis virus (TGEV) nsp1<sup>1–104</sup>
, despite a lack of sequence homology. Structural and biochemical characterization demonstrated that PEDV nsp1 possesses a stable functional region for inhibition of host protein synthesis, which is formed by loops at residues 67 to 71, 78 to 85, and 103 to 110. The different functional regions in PEDV nsp1 and SARS-CoV nsp1 may explain their distinct mechanisms. Importantly, our structural data are conducive to understanding the mechanism of PEDV nsp1 inhibition of the expression of host genes and may aid in the development of a new attenuated vaccine.</p>
</div>
</front>
</TEI>
<affiliations><list><country><li>République populaire de Chine</li>
<li>États-Unis</li>
</country>
<region><li>Géorgie (États-Unis)</li>
</region>
</list>
<tree><country name="République populaire de Chine"><noRegion><name sortKey="Shen, Zhou" sort="Shen, Zhou" uniqKey="Shen Z" first="Zhou" last="Shen">Zhou Shen</name>
</noRegion>
<name sortKey="Cui, Min" sort="Cui, Min" uniqKey="Cui M" first="Min" last="Cui">Min Cui</name>
<name sortKey="Cui, Min" sort="Cui, Min" uniqKey="Cui M" first="Min" last="Cui">Min Cui</name>
<name sortKey="Deng, Feng" sort="Deng, Feng" uniqKey="Deng F" first="Feng" last="Deng">Feng Deng</name>
<name sortKey="Deng, Feng" sort="Deng, Feng" uniqKey="Deng F" first="Feng" last="Deng">Feng Deng</name>
<name sortKey="Fang, Liurong" sort="Fang, Liurong" uniqKey="Fang L" first="Liurong" last="Fang">Liurong Fang</name>
<name sortKey="Fang, Liurong" sort="Fang, Liurong" uniqKey="Fang L" first="Liurong" last="Fang">Liurong Fang</name>
<name sortKey="Fu, Zhen F" sort="Fu, Zhen F" uniqKey="Fu Z" first="Zhen F." last="Fu">Zhen F. Fu</name>
<name sortKey="Fu, Zhen F" sort="Fu, Zhen F" uniqKey="Fu Z" first="Zhen F." last="Fu">Zhen F. Fu</name>
<name sortKey="Peng, Guiqing" sort="Peng, Guiqing" uniqKey="Peng G" first="Guiqing" last="Peng">Guiqing Peng</name>
<name sortKey="Peng, Guiqing" sort="Peng, Guiqing" uniqKey="Peng G" first="Guiqing" last="Peng">Guiqing Peng</name>
<name sortKey="Peng, Guiqing" sort="Peng, Guiqing" uniqKey="Peng G" first="Guiqing" last="Peng">Guiqing Peng</name>
<name sortKey="Shen, Zhou" sort="Shen, Zhou" uniqKey="Shen Z" first="Zhou" last="Shen">Zhou Shen</name>
<name sortKey="Wang, Gang" sort="Wang, Gang" uniqKey="Wang G" first="Gang" last="Wang">Gang Wang</name>
<name sortKey="Wang, Gang" sort="Wang, Gang" uniqKey="Wang G" first="Gang" last="Wang">Gang Wang</name>
<name sortKey="Xiao, Shaobo" sort="Xiao, Shaobo" uniqKey="Xiao S" first="Shaobo" last="Xiao">Shaobo Xiao</name>
<name sortKey="Xiao, Shaobo" sort="Xiao, Shaobo" uniqKey="Xiao S" first="Shaobo" last="Xiao">Shaobo Xiao</name>
<name sortKey="Ye, Gang" sort="Ye, Gang" uniqKey="Ye G" first="Gang" last="Ye">Gang Ye</name>
<name sortKey="Ye, Gang" sort="Ye, Gang" uniqKey="Ye G" first="Gang" last="Ye">Gang Ye</name>
</country>
<country name="États-Unis"><region name="Géorgie (États-Unis)"><name sortKey="Fu, Zhen F" sort="Fu, Zhen F" uniqKey="Fu Z" first="Zhen F." last="Fu">Zhen F. Fu</name>
</region>
</country>
</tree>
</affiliations>
</record>
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