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<title xml:lang="en">Structural Basis for the Inhibition of Host Gene Expression by Porcine Epidemic Diarrhea Virus nsp1</title>
<author>
<name sortKey="Shen, Zhou" sort="Shen, Zhou" uniqKey="Shen Z" first="Zhou" last="Shen">Zhou Shen</name>
<affiliation>
<nlm:aff id="aff1">State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei, China</nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="aff2">College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, China</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Ye, Gang" sort="Ye, Gang" uniqKey="Ye G" first="Gang" last="Ye">Gang Ye</name>
<affiliation>
<nlm:aff id="aff1">State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei, China</nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="aff2">College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, China</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Deng, Feng" sort="Deng, Feng" uniqKey="Deng F" first="Feng" last="Deng">Feng Deng</name>
<affiliation>
<nlm:aff id="aff1">State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei, China</nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="aff2">College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, China</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Wang, Gang" sort="Wang, Gang" uniqKey="Wang G" first="Gang" last="Wang">Gang Wang</name>
<affiliation>
<nlm:aff id="aff1">State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei, China</nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="aff2">College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, China</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Cui, Min" sort="Cui, Min" uniqKey="Cui M" first="Min" last="Cui">Min Cui</name>
<affiliation>
<nlm:aff id="aff1">State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei, China</nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="aff2">College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, China</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Fang, Liurong" sort="Fang, Liurong" uniqKey="Fang L" first="Liurong" last="Fang">Liurong Fang</name>
<affiliation>
<nlm:aff id="aff1">State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei, China</nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="aff2">College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, China</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Xiao, Shaobo" sort="Xiao, Shaobo" uniqKey="Xiao S" first="Shaobo" last="Xiao">Shaobo Xiao</name>
<affiliation>
<nlm:aff id="aff1">State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei, China</nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="aff2">College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, China</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Fu, Zhen F" sort="Fu, Zhen F" uniqKey="Fu Z" first="Zhen F." last="Fu">Zhen F. Fu</name>
<affiliation>
<nlm:aff id="aff1">State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei, China</nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="aff2">College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, China</nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="aff3">Department of Pathology, College of Veterinary Medicine, University of Georgia, Athens, Georgia, USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Peng, Guiqing" sort="Peng, Guiqing" uniqKey="Peng G" first="Guiqing" last="Peng">Guiqing Peng</name>
<affiliation>
<nlm:aff id="aff1">State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei, China</nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="aff2">College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, China</nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="aff4">The Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural University, Wuhan, Hubei, China</nlm:aff>
</affiliation>
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<title xml:lang="en" level="a" type="main">Structural Basis for the Inhibition of Host Gene Expression by Porcine Epidemic Diarrhea Virus nsp1</title>
<author>
<name sortKey="Shen, Zhou" sort="Shen, Zhou" uniqKey="Shen Z" first="Zhou" last="Shen">Zhou Shen</name>
<affiliation>
<nlm:aff id="aff1">State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei, China</nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="aff2">College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, China</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Ye, Gang" sort="Ye, Gang" uniqKey="Ye G" first="Gang" last="Ye">Gang Ye</name>
<affiliation>
<nlm:aff id="aff1">State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei, China</nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="aff2">College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, China</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Deng, Feng" sort="Deng, Feng" uniqKey="Deng F" first="Feng" last="Deng">Feng Deng</name>
<affiliation>
<nlm:aff id="aff1">State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei, China</nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="aff2">College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, China</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Wang, Gang" sort="Wang, Gang" uniqKey="Wang G" first="Gang" last="Wang">Gang Wang</name>
<affiliation>
<nlm:aff id="aff1">State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei, China</nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="aff2">College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, China</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Cui, Min" sort="Cui, Min" uniqKey="Cui M" first="Min" last="Cui">Min Cui</name>
<affiliation>
<nlm:aff id="aff1">State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei, China</nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="aff2">College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, China</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Fang, Liurong" sort="Fang, Liurong" uniqKey="Fang L" first="Liurong" last="Fang">Liurong Fang</name>
<affiliation>
<nlm:aff id="aff1">State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei, China</nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="aff2">College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, China</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Xiao, Shaobo" sort="Xiao, Shaobo" uniqKey="Xiao S" first="Shaobo" last="Xiao">Shaobo Xiao</name>
<affiliation>
<nlm:aff id="aff1">State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei, China</nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="aff2">College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, China</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Fu, Zhen F" sort="Fu, Zhen F" uniqKey="Fu Z" first="Zhen F." last="Fu">Zhen F. Fu</name>
<affiliation>
<nlm:aff id="aff1">State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei, China</nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="aff2">College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, China</nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="aff3">Department of Pathology, College of Veterinary Medicine, University of Georgia, Athens, Georgia, USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Peng, Guiqing" sort="Peng, Guiqing" uniqKey="Peng G" first="Guiqing" last="Peng">Guiqing Peng</name>
<affiliation>
<nlm:aff id="aff1">State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei, China</nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="aff2">College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, China</nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="aff4">The Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural University, Wuhan, Hubei, China</nlm:aff>
</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>
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<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>
<pmc article-type="research-article">
<pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front>
<journal-meta>
<journal-id journal-id-type="nlm-ta">J Virol</journal-id>
<journal-id journal-id-type="iso-abbrev">J. Virol</journal-id>
<journal-id journal-id-type="hwp">jvi</journal-id>
<journal-id journal-id-type="pmc">jvi</journal-id>
<journal-id journal-id-type="publisher-id">JVI</journal-id>
<journal-title-group>
<journal-title>Journal of Virology</journal-title>
</journal-title-group>
<issn pub-type="ppub">0022-538X</issn>
<issn pub-type="epub">1098-5514</issn>
<publisher>
<publisher-name>American Society for Microbiology</publisher-name>
<publisher-loc>1752 N St., N.W., Washington, DC</publisher-loc>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="pmid">29237834</article-id>
<article-id pub-id-type="pmc">5809747</article-id>
<article-id pub-id-type="publisher-id">01896-17</article-id>
<article-id pub-id-type="doi">10.1128/JVI.01896-17</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Structure and Assembly</subject>
</subj-group>
</article-categories>
<title-group>
<article-title>Structural Basis for the Inhibition of Host Gene Expression by Porcine Epidemic Diarrhea Virus nsp1</article-title>
<alt-title alt-title-type="running-head">Structure of Porcine Epidemic Diarrhea Virus nsp1</alt-title>
<alt-title alt-title-type="short-authors">Shen et al.</alt-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname>Shen</surname>
<given-names>Zhou</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>a</sup>
</xref>
<xref ref-type="aff" rid="aff2">
<sup>b</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Ye</surname>
<given-names>Gang</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>a</sup>
</xref>
<xref ref-type="aff" rid="aff2">
<sup>b</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Deng</surname>
<given-names>Feng</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>a</sup>
</xref>
<xref ref-type="aff" rid="aff2">
<sup>b</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Wang</surname>
<given-names>Gang</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>a</sup>
</xref>
<xref ref-type="aff" rid="aff2">
<sup>b</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Cui</surname>
<given-names>Min</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>a</sup>
</xref>
<xref ref-type="aff" rid="aff2">
<sup>b</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Fang</surname>
<given-names>Liurong</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>a</sup>
</xref>
<xref ref-type="aff" rid="aff2">
<sup>b</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<contrib-id contrib-id-type="orcid" authenticated="false">https://orcid.org/0000-0003-0023-9188</contrib-id>
<name>
<surname>Xiao</surname>
<given-names>Shaobo</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>a</sup>
</xref>
<xref ref-type="aff" rid="aff2">
<sup>b</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Fu</surname>
<given-names>Zhen F.</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>a</sup>
</xref>
<xref ref-type="aff" rid="aff2">
<sup>b</sup>
</xref>
<xref ref-type="aff" rid="aff3">
<sup>c</sup>
</xref>
</contrib>
<contrib contrib-type="author" corresp="yes">
<name>
<surname>Peng</surname>
<given-names>Guiqing</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>a</sup>
</xref>
<xref ref-type="aff" rid="aff2">
<sup>b</sup>
</xref>
<xref ref-type="aff" rid="aff4">
<sup>d</sup>
</xref>
</contrib>
<aff id="aff1">
<label>a</label>
State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei, China</aff>
<aff id="aff2">
<label>b</label>
College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, China</aff>
<aff id="aff3">
<label>c</label>
Department of Pathology, College of Veterinary Medicine, University of Georgia, Athens, Georgia, USA</aff>
<aff id="aff4">
<label>d</label>
The Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural University, Wuhan, Hubei, China</aff>
</contrib-group>
<contrib-group>
<contrib contrib-type="editor">
<name>
<surname>Gallagher</surname>
<given-names>Tom</given-names>
</name>
<role>Editor</role>
<aff>Loyola University Medical Center</aff>
</contrib>
</contrib-group>
<author-notes>
<corresp id="cor1">Address correspondence to Guiqing Peng,
<email>penggq@mail.hzau.edu.cn</email>
.</corresp>
<fn fn-type="other">
<p>
<bold>Citation</bold>
Shen Z, Ye G, Deng F, Wang G, Cui M, Fang L, Xiao S, Fu ZF, Peng G. 2018. Structural basis for the inhibition of host gene expression by porcine epidemic diarrhea virus nsp1. J Virol 92:e01896-17.
<ext-link ext-link-type="uri" xlink:href="https://doi.org/10.1128/JVI.01896-17">https://doi.org/10.1128/JVI.01896-17</ext-link>
.</p>
</fn>
</author-notes>
<pub-date pub-type="epreprint">
<day>13</day>
<month>12</month>
<year>2017</year>
</pub-date>
<pub-date pub-type="epub">
<day>12</day>
<month>2</month>
<year>2018</year>
</pub-date>
<pub-date pub-type="collection">
<day>1</day>
<month>3</month>
<year>2018</year>
</pub-date>
<volume>92</volume>
<issue>5</issue>
<elocation-id>e01896-17</elocation-id>
<history>
<date date-type="received">
<day>1</day>
<month>11</month>
<year>2017</year>
</date>
<date date-type="accepted">
<day>29</day>
<month>11</month>
<year>2017</year>
</date>
</history>
<permissions>
<copyright-statement>Copyright © 2018 American Society for Microbiology.</copyright-statement>
<copyright-year>2018</copyright-year>
<copyright-holder>American Society for Microbiology</copyright-holder>
<license license-type="asm" xlink:href="https://doi.org/10.1128/ASMCopyrightv2">
<license-p>
<ext-link ext-link-type="uri" xlink:href="https://doi.org/10.1128/ASMCopyrightv2">All Rights Reserved</ext-link>
.</license-p>
</license>
</permissions>
<self-uri content-type="pdf" xlink:href="zjv005183335001.pdf"></self-uri>
<abstract>
<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>
</abstract>
<kwd-group>
<title>KEYWORDS</title>
<kwd>porcine epidemic diarrhea virus</kwd>
<kwd>nonstructural protein 1</kwd>
<kwd>structure</kwd>
<kwd>C terminus</kwd>
<kwd>host gene expression inhibition</kwd>
</kwd-group>
<funding-group>
<award-group id="award1">
<funding-source id="gs1">
<institution-wrap>
<institution>National Key R&D Plan of China</institution>
</institution-wrap>
</funding-source>
<award-id rid="gs1">2016YFD0500103</award-id>
<principal-award-recipient>
<name>
<surname>Fang</surname>
<given-names>Liurong</given-names>
</name>
</principal-award-recipient>
</award-group>
<award-group id="award2">
<funding-source id="gs2">
<institution-wrap>
<institution>Huazhong Agricultural University & Technological Self-Innovation Foundation</institution>
</institution-wrap>
</funding-source>
<award-id rid="gs2">2662015JQ003</award-id>
<award-id rid="gs2">2662017PY028</award-id>
<principal-award-recipient>
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