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Co-degradation of interferon signaling factor DDX3 by PB1-F2 as a basis for high virulence of 1918 pandemic influenza.

Identifieur interne : 000159 ( PubMed/Corpus ); précédent : 000158; suivant : 000160

Co-degradation of interferon signaling factor DDX3 by PB1-F2 as a basis for high virulence of 1918 pandemic influenza.

Auteurs : Eun-Sook Park ; Young Ho Byun ; Soree Park ; Yo Han Jang ; Woo-Ry Han ; Juhee Won ; Kyung Cho Cho ; Doo Hyun Kim ; Ah Ram Lee ; Gu-Choul Shin ; Yong Kwang Park ; Hong Seok Kang ; Heewoo Sim ; Yea Na Ha ; Byeongjune Jae ; Ahyun Son ; Paul Kim ; Jieun Yu ; Hye-Min Lee ; Sun-Bin Kwon ; Kwang Pyo Kim ; Seung-Hyun Lee ; Yeong-Min Park ; Baik L. Seong ; Kyun-Hwan Kim

Source :

RBID : pubmed:30979777

English descriptors

Abstract

The multifunctional influenza virus protein PB1-F2 plays several roles in deregulation of host innate immune responses and is a known immunopathology enhancer of the 1918 influenza pandemic. Here, we show that the 1918 PB1-F2 protein not only interferes with the mitochondria-dependent pathway of type I interferon (IFN) signaling, but also acquired a novel IFN antagonist function by targeting the DEAD-box helicase DDX3, a key downstream mediator in antiviral interferon signaling, toward proteasome-dependent degradation. Interactome analysis revealed that 1918 PB1-F2, but not PR8 PB1-F2, binds to DDX3 and causes its co-degradation. Consistent with intrinsic protein instability as basis for this gain-of-function, internal structural disorder is associated with the unique cytotoxic sequences of the 1918 PB1-F2 protein. Infusing mice with recombinant DDX3 protein completely rescued them from lethal infection with the 1918 PB1-F2-producing virus. Alongside NS1 protein, 1918 PB1-F2 therefore constitutes a potent IFN antagonist causative for the severe pathogenicity of the 1918 influenza strain. Our identification of molecular determinants of pathogenesis should be useful for the future design of new antiviral strategies against influenza pandemics.

DOI: 10.15252/embj.201899475
PubMed: 30979777

Links to Exploration step

pubmed:30979777

Le document en format XML

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<nlm:affiliation>Department of Pharmacology, Center for Cancer Research and Diagnostic Medicine, IBST, School of Medicine, Konkuk University, Seoul, Korea.</nlm:affiliation>
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<name sortKey="Jang, Yo Han" sort="Jang, Yo Han" uniqKey="Jang Y" first="Yo Han" last="Jang">Yo Han Jang</name>
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<name sortKey="Han, Woo Ry" sort="Han, Woo Ry" uniqKey="Han W" first="Woo-Ry" last="Han">Woo-Ry Han</name>
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<name sortKey="Won, Juhee" sort="Won, Juhee" uniqKey="Won J" first="Juhee" last="Won">Juhee Won</name>
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<name sortKey="Cho, Kyung Cho" sort="Cho, Kyung Cho" uniqKey="Cho K" first="Kyung Cho" last="Cho">Kyung Cho Cho</name>
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<name sortKey="Lee, Ah Ram" sort="Lee, Ah Ram" uniqKey="Lee A" first="Ah Ram" last="Lee">Ah Ram Lee</name>
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<name sortKey="Shin, Gu Choul" sort="Shin, Gu Choul" uniqKey="Shin G" first="Gu-Choul" last="Shin">Gu-Choul Shin</name>
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<name sortKey="Sim, Heewoo" sort="Sim, Heewoo" uniqKey="Sim H" first="Heewoo" last="Sim">Heewoo Sim</name>
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<name sortKey="Ha, Yea Na" sort="Ha, Yea Na" uniqKey="Ha Y" first="Yea Na" last="Ha">Yea Na Ha</name>
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<name sortKey="Son, Ahyun" sort="Son, Ahyun" uniqKey="Son A" first="Ahyun" last="Son">Ahyun Son</name>
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<name sortKey="Kim, Paul" sort="Kim, Paul" uniqKey="Kim P" first="Paul" last="Kim">Paul Kim</name>
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<name sortKey="Yu, Jieun" sort="Yu, Jieun" uniqKey="Yu J" first="Jieun" last="Yu">Jieun Yu</name>
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<name sortKey="Lee, Hye Min" sort="Lee, Hye Min" uniqKey="Lee H" first="Hye-Min" last="Lee">Hye-Min Lee</name>
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<name sortKey="Kwon, Sun Bin" sort="Kwon, Sun Bin" uniqKey="Kwon S" first="Sun-Bin" last="Kwon">Sun-Bin Kwon</name>
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<nlm:affiliation>Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, Korea.</nlm:affiliation>
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<name sortKey="Kim, Kwang Pyo" sort="Kim, Kwang Pyo" uniqKey="Kim K" first="Kwang Pyo" last="Kim">Kwang Pyo Kim</name>
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<nlm:affiliation>Department of Applied Chemistry, Kyung Hee University, Yongin, Korea.</nlm:affiliation>
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<name sortKey="Lee, Seung Hyun" sort="Lee, Seung Hyun" uniqKey="Lee S" first="Seung-Hyun" last="Lee">Seung-Hyun Lee</name>
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<nlm:affiliation>Department of Microbiology, School of Medicine, Konkuk University, Seoul, Korea.</nlm:affiliation>
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<name sortKey="Park, Yeong Min" sort="Park, Yeong Min" uniqKey="Park Y" first="Yeong-Min" last="Park">Yeong-Min Park</name>
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<name sortKey="Seong, Baik L" sort="Seong, Baik L" uniqKey="Seong B" first="Baik L" last="Seong">Baik L. Seong</name>
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<name sortKey="Jang, Yo Han" sort="Jang, Yo Han" uniqKey="Jang Y" first="Yo Han" last="Jang">Yo Han Jang</name>
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<name sortKey="Han, Woo Ry" sort="Han, Woo Ry" uniqKey="Han W" first="Woo-Ry" last="Han">Woo-Ry Han</name>
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<name sortKey="Won, Juhee" sort="Won, Juhee" uniqKey="Won J" first="Juhee" last="Won">Juhee Won</name>
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<name sortKey="Cho, Kyung Cho" sort="Cho, Kyung Cho" uniqKey="Cho K" first="Kyung Cho" last="Cho">Kyung Cho Cho</name>
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<name sortKey="Lee, Ah Ram" sort="Lee, Ah Ram" uniqKey="Lee A" first="Ah Ram" last="Lee">Ah Ram Lee</name>
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<nlm:affiliation>Department of Pharmacology, Center for Cancer Research and Diagnostic Medicine, IBST, School of Medicine, Konkuk University, Seoul, Korea.</nlm:affiliation>
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<name sortKey="Shin, Gu Choul" sort="Shin, Gu Choul" uniqKey="Shin G" first="Gu-Choul" last="Shin">Gu-Choul Shin</name>
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<name sortKey="Kang, Hong Seok" sort="Kang, Hong Seok" uniqKey="Kang H" first="Hong Seok" last="Kang">Hong Seok Kang</name>
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<nlm:affiliation>Department of Pharmacology, Center for Cancer Research and Diagnostic Medicine, IBST, School of Medicine, Konkuk University, Seoul, Korea.</nlm:affiliation>
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<name sortKey="Sim, Heewoo" sort="Sim, Heewoo" uniqKey="Sim H" first="Heewoo" last="Sim">Heewoo Sim</name>
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<nlm:affiliation>Department of Pharmacology, Center for Cancer Research and Diagnostic Medicine, IBST, School of Medicine, Konkuk University, Seoul, Korea.</nlm:affiliation>
</affiliation>
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<name sortKey="Ha, Yea Na" sort="Ha, Yea Na" uniqKey="Ha Y" first="Yea Na" last="Ha">Yea Na Ha</name>
<affiliation>
<nlm:affiliation>Department of Pharmacology, Center for Cancer Research and Diagnostic Medicine, IBST, School of Medicine, Konkuk University, Seoul, Korea.</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Jae, Byeongjune" sort="Jae, Byeongjune" uniqKey="Jae B" first="Byeongjune" last="Jae">Byeongjune Jae</name>
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<nlm:affiliation>Department of Pharmacology, Center for Cancer Research and Diagnostic Medicine, IBST, School of Medicine, Konkuk University, Seoul, Korea.</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Son, Ahyun" sort="Son, Ahyun" uniqKey="Son A" first="Ahyun" last="Son">Ahyun Son</name>
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<nlm:affiliation>Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, Korea.</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Kim, Paul" sort="Kim, Paul" uniqKey="Kim P" first="Paul" last="Kim">Paul Kim</name>
<affiliation>
<nlm:affiliation>Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, Korea.</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Yu, Jieun" sort="Yu, Jieun" uniqKey="Yu J" first="Jieun" last="Yu">Jieun Yu</name>
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<nlm:affiliation>Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, Korea.</nlm:affiliation>
</affiliation>
</author>
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<name sortKey="Lee, Hye Min" sort="Lee, Hye Min" uniqKey="Lee H" first="Hye-Min" last="Lee">Hye-Min Lee</name>
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<nlm:affiliation>Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, Korea.</nlm:affiliation>
</affiliation>
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<name sortKey="Kwon, Sun Bin" sort="Kwon, Sun Bin" uniqKey="Kwon S" first="Sun-Bin" last="Kwon">Sun-Bin Kwon</name>
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<nlm:affiliation>Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, Korea.</nlm:affiliation>
</affiliation>
</author>
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<name sortKey="Kim, Kwang Pyo" sort="Kim, Kwang Pyo" uniqKey="Kim K" first="Kwang Pyo" last="Kim">Kwang Pyo Kim</name>
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<nlm:affiliation>Department of Applied Chemistry, Kyung Hee University, Yongin, Korea.</nlm:affiliation>
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<name sortKey="Lee, Seung Hyun" sort="Lee, Seung Hyun" uniqKey="Lee S" first="Seung-Hyun" last="Lee">Seung-Hyun Lee</name>
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<nlm:affiliation>Department of Microbiology, School of Medicine, Konkuk University, Seoul, Korea.</nlm:affiliation>
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<name sortKey="Park, Yeong Min" sort="Park, Yeong Min" uniqKey="Park Y" first="Yeong-Min" last="Park">Yeong-Min Park</name>
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<name sortKey="Seong, Baik L" sort="Seong, Baik L" uniqKey="Seong B" first="Baik L" last="Seong">Baik L. Seong</name>
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<name sortKey="Kim, Kyun Hwan" sort="Kim, Kyun Hwan" uniqKey="Kim K" first="Kyun-Hwan" last="Kim">Kyun-Hwan Kim</name>
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<nlm:affiliation>Department of Pharmacology, Center for Cancer Research and Diagnostic Medicine, IBST, School of Medicine, Konkuk University, Seoul, Korea blseong@yonsei.ac.kr khkim10@kku.ac.kr.</nlm:affiliation>
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<front>
<div type="abstract" xml:lang="en">The multifunctional influenza virus protein PB1-F2 plays several roles in deregulation of host innate immune responses and is a known immunopathology enhancer of the 1918 influenza pandemic. Here, we show that the 1918 PB1-F2 protein not only interferes with the mitochondria-dependent pathway of type I interferon (IFN) signaling, but also acquired a novel IFN antagonist function by targeting the DEAD-box helicase DDX3, a key downstream mediator in antiviral interferon signaling, toward proteasome-dependent degradation. Interactome analysis revealed that 1918 PB1-F2, but not PR8 PB1-F2, binds to DDX3 and causes its co-degradation. Consistent with intrinsic protein instability as basis for this gain-of-function, internal structural disorder is associated with the unique cytotoxic sequences of the 1918 PB1-F2 protein. Infusing mice with recombinant DDX3 protein completely rescued them from lethal infection with the 1918 PB1-F2-producing virus. Alongside NS1 protein, 1918 PB1-F2 therefore constitutes a potent IFN antagonist causative for the severe pathogenicity of the 1918 influenza strain. Our identification of molecular determinants of pathogenesis should be useful for the future design of new antiviral strategies against influenza pandemics.</div>
</front>
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<Year>2020</Year>
<Month>01</Month>
<Day>06</Day>
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<Month>05</Month>
<Day>16</Day>
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<ISSN IssnType="Electronic">1460-2075</ISSN>
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<Issue>10</Issue>
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<Year>2019</Year>
<Month>05</Month>
<Day>15</Day>
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<Title>The EMBO journal</Title>
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<ArticleTitle>Co-degradation of interferon signaling factor DDX3 by PB1-F2 as a basis for high virulence of 1918 pandemic influenza.</ArticleTitle>
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<ELocationID EIdType="doi" ValidYN="Y">10.15252/embj.201899475</ELocationID>
<Abstract>
<AbstractText>The multifunctional influenza virus protein PB1-F2 plays several roles in deregulation of host innate immune responses and is a known immunopathology enhancer of the 1918 influenza pandemic. Here, we show that the 1918 PB1-F2 protein not only interferes with the mitochondria-dependent pathway of type I interferon (IFN) signaling, but also acquired a novel IFN antagonist function by targeting the DEAD-box helicase DDX3, a key downstream mediator in antiviral interferon signaling, toward proteasome-dependent degradation. Interactome analysis revealed that 1918 PB1-F2, but not PR8 PB1-F2, binds to DDX3 and causes its co-degradation. Consistent with intrinsic protein instability as basis for this gain-of-function, internal structural disorder is associated with the unique cytotoxic sequences of the 1918 PB1-F2 protein. Infusing mice with recombinant DDX3 protein completely rescued them from lethal infection with the 1918 PB1-F2-producing virus. Alongside NS1 protein, 1918 PB1-F2 therefore constitutes a potent IFN antagonist causative for the severe pathogenicity of the 1918 influenza strain. Our identification of molecular determinants of pathogenesis should be useful for the future design of new antiviral strategies against influenza pandemics.</AbstractText>
<CopyrightInformation>© 2019 The Authors.</CopyrightInformation>
</Abstract>
<AuthorList CompleteYN="Y">
<Author ValidYN="Y">
<LastName>Park</LastName>
<ForeName>Eun-Sook</ForeName>
<Initials>ES</Initials>
<AffiliationInfo>
<Affiliation>Department of Pharmacology, Center for Cancer Research and Diagnostic Medicine, IBST, School of Medicine, Konkuk University, Seoul, Korea.</Affiliation>
</AffiliationInfo>
<AffiliationInfo>
<Affiliation>KU Open Innovation Center, Konkuk University, Seoul, Korea.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Byun</LastName>
<ForeName>Young Ho</ForeName>
<Initials>YH</Initials>
<Identifier Source="ORCID">0000-0001-9306-9485</Identifier>
<AffiliationInfo>
<Affiliation>Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, Korea.</Affiliation>
</AffiliationInfo>
<AffiliationInfo>
<Affiliation>Vaccine Translational Research Center, Yonsei University, Seoul, Korea.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Park</LastName>
<ForeName>Soree</ForeName>
<Initials>S</Initials>
<AffiliationInfo>
<Affiliation>Department of Pharmacology, Center for Cancer Research and Diagnostic Medicine, IBST, School of Medicine, Konkuk University, Seoul, Korea.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Jang</LastName>
<ForeName>Yo Han</ForeName>
<Initials>YH</Initials>
<AffiliationInfo>
<Affiliation>Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, Korea.</Affiliation>
</AffiliationInfo>
<AffiliationInfo>
<Affiliation>Vaccine Translational Research Center, Yonsei University, Seoul, Korea.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Han</LastName>
<ForeName>Woo-Ry</ForeName>
<Initials>WR</Initials>
<AffiliationInfo>
<Affiliation>Department of Pharmacology, Center for Cancer Research and Diagnostic Medicine, IBST, School of Medicine, Konkuk University, Seoul, Korea.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Won</LastName>
<ForeName>Juhee</ForeName>
<Initials>J</Initials>
<Identifier Source="ORCID">0000-0002-5757-3745</Identifier>
<AffiliationInfo>
<Affiliation>Department of Pharmacology, Center for Cancer Research and Diagnostic Medicine, IBST, School of Medicine, Konkuk University, Seoul, Korea.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Cho</LastName>
<ForeName>Kyung Cho</ForeName>
<Initials>KC</Initials>
<Identifier Source="ORCID">0000-0003-0483-9543</Identifier>
<AffiliationInfo>
<Affiliation>Department of Applied Chemistry, Kyung Hee University, Yongin, Korea.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Kim</LastName>
<ForeName>Doo Hyun</ForeName>
<Initials>DH</Initials>
<AffiliationInfo>
<Affiliation>Department of Pharmacology, Center for Cancer Research and Diagnostic Medicine, IBST, School of Medicine, Konkuk University, Seoul, Korea.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Lee</LastName>
<ForeName>Ah Ram</ForeName>
<Initials>AR</Initials>
<AffiliationInfo>
<Affiliation>Department of Pharmacology, Center for Cancer Research and Diagnostic Medicine, IBST, School of Medicine, Konkuk University, Seoul, Korea.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Shin</LastName>
<ForeName>Gu-Choul</ForeName>
<Initials>GC</Initials>
<Identifier Source="ORCID">0000-0001-8200-9700</Identifier>
<AffiliationInfo>
<Affiliation>Department of Pharmacology, Center for Cancer Research and Diagnostic Medicine, IBST, School of Medicine, Konkuk University, Seoul, Korea.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Park</LastName>
<ForeName>Yong Kwang</ForeName>
<Initials>YK</Initials>
<AffiliationInfo>
<Affiliation>Department of Pharmacology, Center for Cancer Research and Diagnostic Medicine, IBST, School of Medicine, Konkuk University, Seoul, Korea.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Kang</LastName>
<ForeName>Hong Seok</ForeName>
<Initials>HS</Initials>
<AffiliationInfo>
<Affiliation>Department of Pharmacology, Center for Cancer Research and Diagnostic Medicine, IBST, School of Medicine, Konkuk University, Seoul, Korea.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Sim</LastName>
<ForeName>Heewoo</ForeName>
<Initials>H</Initials>
<AffiliationInfo>
<Affiliation>Department of Pharmacology, Center for Cancer Research and Diagnostic Medicine, IBST, School of Medicine, Konkuk University, Seoul, Korea.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Ha</LastName>
<ForeName>Yea Na</ForeName>
<Initials>YN</Initials>
<AffiliationInfo>
<Affiliation>Department of Pharmacology, Center for Cancer Research and Diagnostic Medicine, IBST, School of Medicine, Konkuk University, Seoul, Korea.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Jae</LastName>
<ForeName>Byeongjune</ForeName>
<Initials>B</Initials>
<AffiliationInfo>
<Affiliation>Department of Pharmacology, Center for Cancer Research and Diagnostic Medicine, IBST, School of Medicine, Konkuk University, Seoul, Korea.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Son</LastName>
<ForeName>Ahyun</ForeName>
<Initials>A</Initials>
<AffiliationInfo>
<Affiliation>Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, Korea.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Kim</LastName>
<ForeName>Paul</ForeName>
<Initials>P</Initials>
<AffiliationInfo>
<Affiliation>Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, Korea.</Affiliation>
</AffiliationInfo>
<AffiliationInfo>
<Affiliation>Vaccine Translational Research Center, Yonsei University, Seoul, Korea.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Yu</LastName>
<ForeName>Jieun</ForeName>
<Initials>J</Initials>
<AffiliationInfo>
<Affiliation>Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, Korea.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Lee</LastName>
<ForeName>Hye-Min</ForeName>
<Initials>HM</Initials>
<AffiliationInfo>
<Affiliation>Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, Korea.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Kwon</LastName>
<ForeName>Sun-Bin</ForeName>
<Initials>SB</Initials>
<AffiliationInfo>
<Affiliation>Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, Korea.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Kim</LastName>
<ForeName>Kwang Pyo</ForeName>
<Initials>KP</Initials>
<AffiliationInfo>
<Affiliation>Department of Applied Chemistry, Kyung Hee University, Yongin, Korea.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Lee</LastName>
<ForeName>Seung-Hyun</ForeName>
<Initials>SH</Initials>
<AffiliationInfo>
<Affiliation>Department of Microbiology, School of Medicine, Konkuk University, Seoul, Korea.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Park</LastName>
<ForeName>Yeong-Min</ForeName>
<Initials>YM</Initials>
<AffiliationInfo>
<Affiliation>Laboratory of Dendritic Cell Differentiation and Regulation, Department of Immunology, School of Medicine, Konkuk University, Seoul, Korea.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Seong</LastName>
<ForeName>Baik L</ForeName>
<Initials>BL</Initials>
<Identifier Source="ORCID">0000-0002-7301-082X</Identifier>
<AffiliationInfo>
<Affiliation>Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, Korea blseong@yonsei.ac.kr khkim10@kku.ac.kr.</Affiliation>
</AffiliationInfo>
<AffiliationInfo>
<Affiliation>Vaccine Translational Research Center, Yonsei University, Seoul, Korea.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Kim</LastName>
<ForeName>Kyun-Hwan</ForeName>
<Initials>KH</Initials>
<Identifier Source="ORCID">0000-0001-5266-072X</Identifier>
<AffiliationInfo>
<Affiliation>Department of Pharmacology, Center for Cancer Research and Diagnostic Medicine, IBST, School of Medicine, Konkuk University, Seoul, Korea blseong@yonsei.ac.kr khkim10@kku.ac.kr.</Affiliation>
</AffiliationInfo>
<AffiliationInfo>
<Affiliation>KU Open Innovation Center, Konkuk University, Seoul, Korea.</Affiliation>
</AffiliationInfo>
<AffiliationInfo>
<Affiliation>Research Institute of Medical Science, Konkuk University, Seoul, Korea.</Affiliation>
</AffiliationInfo>
</Author>
</AuthorList>
<Language>eng</Language>
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<ArticleDate DateType="Electronic">
<Year>2019</Year>
<Month>04</Month>
<Day>12</Day>
</ArticleDate>
</Article>
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<Country>England</Country>
<MedlineTA>EMBO J</MedlineTA>
<NlmUniqueID>8208664</NlmUniqueID>
<ISSNLinking>0261-4189</ISSNLinking>
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<NameOfSubstance UI="C442816">PB1-F2 protein, Influenza A virus</NameOfSubstance>
</Chemical>
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<RegistryNumber>9008-11-1</RegistryNumber>
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</Chemical>
<Chemical>
<RegistryNumber>EC 3.6.1.-</RegistryNumber>
<NameOfSubstance UI="C119332">DDX3X protein, human</NameOfSubstance>
</Chemical>
<Chemical>
<RegistryNumber>EC 3.6.4.13</RegistryNumber>
<NameOfSubstance UI="D053487">DEAD-box RNA Helicases</NameOfSubstance>
</Chemical>
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<DescriptorName UI="D053487" MajorTopicYN="N">DEAD-box RNA Helicases</DescriptorName>
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</ArticleIdList>
<ReferenceList>
<Reference>
<Citation>PLoS Pathog. 2008 Aug 01;4(8):e1000115</Citation>
<ArticleIdList>
<ArticleId IdType="pubmed">18670648</ArticleId>
</ArticleIdList>
</Reference>
<Reference>
<Citation>J Gen Virol. 2008 Oct;89(Pt 10):2359-2376</Citation>
<ArticleIdList>
<ArticleId IdType="pubmed">18796704</ArticleId>
</ArticleIdList>
</Reference>
<Reference>
<Citation>Nat Med. 2001 Dec;7(12):1306-12</Citation>
<ArticleIdList>
<ArticleId IdType="pubmed">11726970</ArticleId>
</ArticleIdList>
</Reference>
<Reference>
<Citation>J Virol. 2014 Jan;88(1):503-15</Citation>
<ArticleIdList>
<ArticleId IdType="pubmed">24173220</ArticleId>
</ArticleIdList>
</Reference>
<Reference>
<Citation>J Virol. 2011 Jan;85(2):652-62</Citation>
<ArticleIdList>
<ArticleId IdType="pubmed">21084483</ArticleId>
</ArticleIdList>
</Reference>
<Reference>
<Citation>Euro Surveill. 2016 Dec 1;21(48):</Citation>
<ArticleIdList>
<ArticleId IdType="pubmed">27934581</ArticleId>
</ArticleIdList>
</Reference>
<Reference>
<Citation>J Virol. 2003 Jul;77(13):7214-24</Citation>
<ArticleIdList>
<ArticleId IdType="pubmed">12805420</ArticleId>
</ArticleIdList>
</Reference>
<Reference>
<Citation>J Biol Chem. 2010 Apr 23;285(17):13233-43</Citation>
<ArticleIdList>
<ArticleId IdType="pubmed">20172856</ArticleId>
</ArticleIdList>
</Reference>
<Reference>
<Citation>Science. 2007 Feb 2;315(5812):655-9</Citation>
<ArticleIdList>
<ArticleId IdType="pubmed">17272724</ArticleId>
</ArticleIdList>
</Reference>
<Reference>
<Citation>Cell Host Microbe. 2007 Oct 11;2(4):207-9</Citation>
<ArticleIdList>
<ArticleId IdType="pubmed">18005736</ArticleId>
</ArticleIdList>
</Reference>
<Reference>
<Citation>J Virol. 2012 Aug;86(16):8359-66</Citation>
<ArticleIdList>
<ArticleId IdType="pubmed">22674996</ArticleId>
</ArticleIdList>
</Reference>
<Reference>
<Citation>Mol Cell Biol. 2013 May;33(10):2004-15</Citation>
<ArticleIdList>
<ArticleId IdType="pubmed">23478265</ArticleId>
</ArticleIdList>
</Reference>
<Reference>
<Citation>Biochim Biophys Acta. 2013 Aug;1829(8):854-65</Citation>
<ArticleIdList>
<ArticleId IdType="pubmed">23567047</ArticleId>
</ArticleIdList>
</Reference>
<Reference>
<Citation>Front Immunol. 2015 Aug 19;6:419</Citation>
<ArticleIdList>
<ArticleId IdType="pubmed">26347742</ArticleId>
</ArticleIdList>
</Reference>
<Reference>
<Citation>J Mol Biol. 2014 Mar 20;426(6):1322-50</Citation>
<ArticleIdList>
<ArticleId IdType="pubmed">24184279</ArticleId>
</ArticleIdList>
</Reference>
<Reference>
<Citation>Cell. 2010 Mar 19;140(6):805-20</Citation>
<ArticleIdList>
<ArticleId IdType="pubmed">20303872</ArticleId>
</ArticleIdList>
</Reference>
<Reference>
<Citation>Science. 2006 May 12;312(5775):879-82</Citation>
<ArticleIdList>
<ArticleId IdType="pubmed">16690858</ArticleId>
</ArticleIdList>
</Reference>
<Reference>
<Citation>Front Microbiol. 2017 Apr 21;8:692</Citation>
<ArticleIdList>
<ArticleId IdType="pubmed">28484439</ArticleId>
</ArticleIdList>
</Reference>
<Reference>
<Citation>Virology. 2013 Jun 5;440(2):97-104</Citation>
<ArticleIdList>
<ArticleId IdType="pubmed">23545143</ArticleId>
</ArticleIdList>
</Reference>
<Reference>
<Citation>J Virol. 2006 Aug;80(16):7976-83</Citation>
<ArticleIdList>
<ArticleId IdType="pubmed">16873254</ArticleId>
</ArticleIdList>
</Reference>
<Reference>
<Citation>Biochim Biophys Acta. 2010 Apr;1804(4):996-1010</Citation>
<ArticleIdList>
<ArticleId IdType="pubmed">20100603</ArticleId>
</ArticleIdList>
</Reference>
<Reference>
<Citation>Nat Biotechnol. 2007 Apr;25(4):433-4</Citation>
<ArticleIdList>
<ArticleId IdType="pubmed">17420751</ArticleId>
</ArticleIdList>
</Reference>
<Reference>
<Citation>J Virol. 2016 Jan 20;90(7):3661-75</Citation>
<ArticleIdList>
<ArticleId IdType="pubmed">26792746</ArticleId>
</ArticleIdList>
</Reference>
<Reference>
<Citation>PLoS One. 2008 Jul 16;3(7):e2677</Citation>
<ArticleIdList>
<ArticleId IdType="pubmed">18628952</ArticleId>
</ArticleIdList>
</Reference>
<Reference>
<Citation>Nat Med. 2002 Sep;8(9):950-4</Citation>
<ArticleIdList>
<ArticleId IdType="pubmed">12195436</ArticleId>
</ArticleIdList>
</Reference>
<Reference>
<Citation>PLoS Pathog. 2011 Jun;7(6):e1002067</Citation>
<ArticleIdList>
<ArticleId IdType="pubmed">21695240</ArticleId>
</ArticleIdList>
</Reference>
<Reference>
<Citation>Proteins. 2005;61 Suppl 7:176-82</Citation>
<ArticleIdList>
<ArticleId IdType="pubmed">16187360</ArticleId>
</ArticleIdList>
</Reference>
<Reference>
<Citation>Hist Philos Life Sci. 1991;13(2):223-34</Citation>
<ArticleIdList>
<ArticleId IdType="pubmed">1724803</ArticleId>
</ArticleIdList>
</Reference>
<Reference>
<Citation>PLoS Pathog. 2010 Jul 22;6(7):e1001014</Citation>
<ArticleIdList>
<ArticleId IdType="pubmed">20661425</ArticleId>
</ArticleIdList>
</Reference>
<Reference>
<Citation>PLoS One. 2013 Oct 02;8(10):e75043</Citation>
<ArticleIdList>
<ArticleId IdType="pubmed">24098364</ArticleId>
</ArticleIdList>
</Reference>
<Reference>
<Citation>Int J Mol Sci. 2018 Oct 03;19(10):</Citation>
<ArticleIdList>
<ArticleId IdType="pubmed">30282926</ArticleId>
</ArticleIdList>
</Reference>
<Reference>
<Citation>Nat Rev Microbiol. 2004 Nov;2(11):909-14</Citation>
<ArticleIdList>
<ArticleId IdType="pubmed">15494747</ArticleId>
</ArticleIdList>
</Reference>
<Reference>
<Citation>Cell Host Microbe. 2007 Oct 11;2(4):240-9</Citation>
<ArticleIdList>
<ArticleId IdType="pubmed">18005742</ArticleId>
</ArticleIdList>
</Reference>
<Reference>
<Citation>Nature. 2007 Jan 18;445(7125):319-23</Citation>
<ArticleIdList>
<ArticleId IdType="pubmed">17230189</ArticleId>
</ArticleIdList>
</Reference>
<Reference>
<Citation>Nat Protoc. 2006;1(6):2856-60</Citation>
<ArticleIdList>
<ArticleId IdType="pubmed">17406544</ArticleId>
</ArticleIdList>
</Reference>
<Reference>
<Citation>J Biol Chem. 2016 Jan 8;291(2):739-51</Citation>
<ArticleIdList>
<ArticleId IdType="pubmed">26601953</ArticleId>
</ArticleIdList>
</Reference>
<Reference>
<Citation>Nat Med. 2001 Dec;7(12):1286-8</Citation>
<ArticleIdList>
<ArticleId IdType="pubmed">11726965</ArticleId>
</ArticleIdList>
</Reference>
<Reference>
<Citation>mBio. 2018 Jan 16;9(1):</Citation>
<ArticleIdList>
<ArticleId IdType="pubmed">29339427</ArticleId>
</ArticleIdList>
</Reference>
<Reference>
<Citation>RNA Biol. 2009 Jan-Mar;6(1):21-4</Citation>
<ArticleIdList>
<ArticleId IdType="pubmed">19106620</ArticleId>
</ArticleIdList>
</Reference>
<Reference>
<Citation>PLoS Pathog. 2009 Oct;5(10):e1000604</Citation>
<ArticleIdList>
<ArticleId IdType="pubmed">19798428</ArticleId>
</ArticleIdList>
</Reference>
<Reference>
<Citation>Science. 2005 Oct 7;310(5745):77-80</Citation>
<ArticleIdList>
<ArticleId IdType="pubmed">16210530</ArticleId>
</ArticleIdList>
</Reference>
<Reference>
<Citation>Proc Natl Acad Sci U S A. 2002 Aug 6;99(16):10736-41</Citation>
<ArticleIdList>
<ArticleId IdType="pubmed">12149435</ArticleId>
</ArticleIdList>
</Reference>
</ReferenceList>
</PubmedData>
</pubmed>
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   |texte=   Co-degradation of interferon signaling factor DDX3 by PB1-F2 as a basis for high virulence of 1918 pandemic influenza.
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