The Leader Proteinase of Foot-and-Mouth Disease Virus Negatively Regulates the Type I Interferon Pathway by Acting as a Viral Deubiquitinase
Identifieur interne : 002354 ( Main/Exploration ); précédent : 002353; suivant : 002355The Leader Proteinase of Foot-and-Mouth Disease Virus Negatively Regulates the Type I Interferon Pathway by Acting as a Viral Deubiquitinase
Auteurs : DANG WANG [République populaire de Chine] ; LIURONG FANG [République populaire de Chine] ; PING LI [République populaire de Chine] ; LI SUN [République populaire de Chine] ; JINXIU FAN [République populaire de Chine] ; QINGYE ZHANG [République populaire de Chine] ; RUI LUO [République populaire de Chine] ; XIANGTAO LIU [République populaire de Chine] ; KUI LI [États-Unis] ; HUANCHUN CHEN [République populaire de Chine] ; ZHONGBIN CHEN [République populaire de Chine] ; SHAOBO XIAO [République populaire de Chine]Source :
- Journal of virology [ 0022-538X ] ; 2011.
Descripteurs français
- Pascal (Inist)
- Wicri :
- topic : Vétérinaire.
English descriptors
- KwdEn :
Abstract
The leader proteinase (Lpro) of foot-and-mouth disease virus (FMDV) is a papain-like proteinase that plays an important role in FMDV pathogenesis. Previously, it has been shown that Lpro is involved in the inhibition of the type I interferon (IFN) response by FMDV. However, the underlying mechanisms remain unclear. Here we demonstrate that FMDV Lbpro, a shorter form of Lpro, has deubiquitinating activity. Sequence alignment and structural bioinformatics analyses revealed that the catalytic residues (Cys51 and His148) are highly conserved in FMDV Lbpro of all seven serotypes and that the topology of FMDV Lbpro is remarkably similar to that of ubiquitin-specific protease 14 (USP14), a cellular deubiquitylation enzyme (DUB), and to that of severe acute respiratory syndrome coronavirus (SARS-CoV) papain-like protease (PLpro), a coronaviral DUB. Both purified Lbpro protein and in vivo ectopically expressed Lbpro removed ubiquitin (Ub) moieties from cellular substrates, acting on both lysine-48- and lysine-63-linked polyubiquitin chains. Furthermore, Lbpro significantly inhibited ubiquitination of retinoic acid-inducible gene I (RIG-I), TANK-binding kinase 1 (TBK1), TNF receptor-associated factor 6 (TRAF6), and TRAF3, key signaling molecules in activation of type I IFN response. Mutations in Lbpro that ablate the catalytic activity (C51A or D163N/D164N) or disrupt the SAP (for SAF-A/B, Acinus, and PIAS) domain (I83A/L86A) abrogated the DUB activity of Lbpro as well as its ability to block signaling to the IFN-β promoter. Collectively, these results demonstrate that FMDV Lbpro possesses DUB activity in addition to serving as a viral proteinase and describe a novel mechanism evolved by FMDV to counteract host innate antiviral responses.
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University</s1><s2>Wuhan 430070</s2><s3>CHN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>5 aut.</sZ><sZ>7 aut.</sZ><sZ>10 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>République populaire de Chine</country><placeName><settlement type="city">Wuhan</settlement><region type="région">Hubei</region></placeName></affiliation></author><author><name sortKey="Qingye Zhang" sort="Qingye Zhang" uniqKey="Qingye Zhang" last="Qingye Zhang">QINGYE ZHANG</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>National Engineering Research Centre of Microbial Pesticides, Huazhong Agricultural University</s1><s2>Wuhan, 430070</s2><s3>CHN</s3><sZ>6 aut.</sZ></inist:fA14><country>République populaire de Chine</country><wicri:noRegion>Wuhan, 430070</wicri:noRegion></affiliation></author><author><name sortKey="Rui Luo" sort="Rui Luo" uniqKey="Rui Luo" last="Rui Luo">RUI LUO</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Division of Animal Infectious Diseases, State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University</s1><s2>Wuhan 430070</s2><s3>CHN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>5 aut.</sZ><sZ>7 aut.</sZ><sZ>10 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>République populaire de Chine</country><placeName><settlement type="city">Wuhan</settlement><region type="région">Hubei</region></placeName></affiliation></author><author><name sortKey="Xiangtao Liu" sort="Xiangtao Liu" uniqKey="Xiangtao Liu" last="Xiangtao Liu">XIANGTAO LIU</name><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>State Key Laboratory of Veterinary Etiologic Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences</s1><s2>Lanzhou, Gansu 730046</s2><s3>CHN</s3><sZ>8 aut.</sZ></inist:fA14><country>République populaire de Chine</country><wicri:noRegion>Lanzhou, Gansu 730046</wicri:noRegion></affiliation></author><author><name sortKey="Kui Li" sort="Kui Li" uniqKey="Kui Li" last="Kui Li">KUI LI</name><affiliation wicri:level="1"><inist:fA14 i1="05"><s1>Department of Microbiology, Immunology and Biochemistry, University of Tennessee Health Science Center</s1><s2>Memphis, Tennessee 38163</s2><s3>USA</s3><sZ>9 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Memphis, Tennessee 38163</wicri:noRegion></affiliation></author><author><name sortKey="Huanchun Chen" sort="Huanchun Chen" uniqKey="Huanchun Chen" last="Huanchun Chen">HUANCHUN CHEN</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Division of Animal Infectious Diseases, State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University</s1><s2>Wuhan 430070</s2><s3>CHN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>5 aut.</sZ><sZ>7 aut.</sZ><sZ>10 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>République populaire de Chine</country><placeName><settlement type="city">Wuhan</settlement><region type="région">Hubei</region></placeName></affiliation></author><author><name sortKey="Zhongbin Chen" sort="Zhongbin Chen" uniqKey="Zhongbin Chen" last="Zhongbin Chen">ZHONGBIN CHEN</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Division of Infection and Immunity, Department of Electromagnetic and Laser Biology, Beijing Institute of Radiation Medicine</s1><s2>Beijing 100850</s2><s3>CHN</s3><sZ>4 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>République populaire de Chine</country><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Shaobo Xiao" sort="Shaobo Xiao" uniqKey="Shaobo Xiao" last="Shaobo Xiao">SHAOBO XIAO</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Division of Animal Infectious Diseases, State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University</s1><s2>Wuhan 430070</s2><s3>CHN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>5 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type="wicri:Area/Main/Exploration">002354</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">The Leader Proteinase of Foot-and-Mouth Disease Virus Negatively Regulates the Type I Interferon Pathway by Acting as a Viral Deubiquitinase</title><author><name sortKey="Dang Wang" sort="Dang Wang" uniqKey="Dang Wang" last="Dang Wang">DANG WANG</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Division of Animal Infectious Diseases, State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University</s1><s2>Wuhan 430070</s2><s3>CHN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>5 aut.</sZ><sZ>7 aut.</sZ><sZ>10 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>République populaire de Chine</country><placeName><settlement type="city">Wuhan</settlement><region type="région">Hubei</region></placeName></affiliation></author><author><name sortKey="Liurong Fang" sort="Liurong Fang" uniqKey="Liurong Fang" last="Liurong Fang">LIURONG FANG</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Division of Animal Infectious Diseases, State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University</s1><s2>Wuhan 430070</s2><s3>CHN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>5 aut.</sZ><sZ>7 aut.</sZ><sZ>10 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>République populaire de Chine</country><placeName><settlement type="city">Wuhan</settlement><region type="région">Hubei</region></placeName></affiliation></author><author><name sortKey="Ping Li" sort="Ping Li" uniqKey="Ping Li" last="Ping Li">PING LI</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Division of Animal Infectious Diseases, State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University</s1><s2>Wuhan 430070</s2><s3>CHN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>5 aut.</sZ><sZ>7 aut.</sZ><sZ>10 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>République populaire de Chine</country><placeName><settlement type="city">Wuhan</settlement><region type="région">Hubei</region></placeName></affiliation></author><author><name sortKey="Li Sun" sort="Li Sun" uniqKey="Li Sun" last="Li Sun">LI SUN</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Division of Infection and Immunity, Department of Electromagnetic and Laser Biology, Beijing Institute of Radiation Medicine</s1><s2>Beijing 100850</s2><s3>CHN</s3><sZ>4 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>République populaire de Chine</country><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Jinxiu Fan" sort="Jinxiu Fan" uniqKey="Jinxiu Fan" last="Jinxiu Fan">JINXIU FAN</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Division of Animal Infectious Diseases, State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University</s1><s2>Wuhan 430070</s2><s3>CHN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>5 aut.</sZ><sZ>7 aut.</sZ><sZ>10 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>République populaire de Chine</country><placeName><settlement type="city">Wuhan</settlement><region type="région">Hubei</region></placeName></affiliation></author><author><name sortKey="Qingye Zhang" sort="Qingye Zhang" uniqKey="Qingye Zhang" last="Qingye Zhang">QINGYE ZHANG</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>National Engineering Research Centre of Microbial Pesticides, Huazhong Agricultural University</s1><s2>Wuhan, 430070</s2><s3>CHN</s3><sZ>6 aut.</sZ></inist:fA14><country>République populaire de Chine</country><wicri:noRegion>Wuhan, 430070</wicri:noRegion></affiliation></author><author><name sortKey="Rui Luo" sort="Rui Luo" uniqKey="Rui Luo" last="Rui Luo">RUI LUO</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Division of Animal Infectious Diseases, State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University</s1><s2>Wuhan 430070</s2><s3>CHN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>5 aut.</sZ><sZ>7 aut.</sZ><sZ>10 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>République populaire de Chine</country><placeName><settlement type="city">Wuhan</settlement><region type="région">Hubei</region></placeName></affiliation></author><author><name sortKey="Xiangtao Liu" sort="Xiangtao Liu" uniqKey="Xiangtao Liu" last="Xiangtao Liu">XIANGTAO LIU</name><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>State Key Laboratory of Veterinary Etiologic Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences</s1><s2>Lanzhou, Gansu 730046</s2><s3>CHN</s3><sZ>8 aut.</sZ></inist:fA14><country>République populaire de Chine</country><wicri:noRegion>Lanzhou, Gansu 730046</wicri:noRegion></affiliation></author><author><name sortKey="Kui Li" sort="Kui Li" uniqKey="Kui Li" last="Kui Li">KUI LI</name><affiliation wicri:level="1"><inist:fA14 i1="05"><s1>Department of Microbiology, Immunology and Biochemistry, University of Tennessee Health Science Center</s1><s2>Memphis, Tennessee 38163</s2><s3>USA</s3><sZ>9 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Memphis, Tennessee 38163</wicri:noRegion></affiliation></author><author><name sortKey="Huanchun Chen" sort="Huanchun Chen" uniqKey="Huanchun Chen" last="Huanchun Chen">HUANCHUN CHEN</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Division of Animal Infectious Diseases, State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University</s1><s2>Wuhan 430070</s2><s3>CHN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>5 aut.</sZ><sZ>7 aut.</sZ><sZ>10 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>République populaire de Chine</country><placeName><settlement type="city">Wuhan</settlement><region type="région">Hubei</region></placeName></affiliation></author><author><name sortKey="Zhongbin Chen" sort="Zhongbin Chen" uniqKey="Zhongbin Chen" last="Zhongbin Chen">ZHONGBIN CHEN</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Division of Infection and Immunity, Department of Electromagnetic and Laser Biology, Beijing Institute of Radiation Medicine</s1><s2>Beijing 100850</s2><s3>CHN</s3><sZ>4 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>République populaire de Chine</country><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Shaobo Xiao" sort="Shaobo Xiao" uniqKey="Shaobo Xiao" last="Shaobo Xiao">SHAOBO XIAO</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Division of Animal Infectious Diseases, State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University</s1><s2>Wuhan 430070</s2><s3>CHN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>5 aut.</sZ><sZ>7 aut.</sZ><sZ>10 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>République populaire de Chine</country><placeName><settlement type="city">Wuhan</settlement><region type="région">Hubei</region></placeName></affiliation></author></analytic><series><title level="j" type="main">Journal of virology</title><title level="j" type="abbreviated">J. virol.</title><idno type="ISSN">0022-538X</idno><imprint><date when="2011">2011</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Journal of virology</title><title level="j" type="abbreviated">J. virol.</title><idno type="ISSN">0022-538X</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Aphthovirus</term><term>Interferon</term><term>Regulation(control)</term><term>Veterinary</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Aphthovirus</term><term>Régulation</term><term>Interféron</term><term>Vétérinaire</term></keywords><keywords scheme="Wicri" type="topic" xml:lang="fr"><term>Vétérinaire</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The leader proteinase (L<sup>pro</sup>) of foot-and-mouth disease virus (FMDV) is a papain-like proteinase that plays an important role in FMDV pathogenesis. Previously, it has been shown that L<sup>pro</sup> is involved in the inhibition of the type I interferon (IFN) response by FMDV. However, the underlying mechanisms remain unclear. Here we demonstrate that FMDV Lb<sup>pro</sup>, a shorter form of L<sup>pro</sup>, has deubiquitinating activity. Sequence alignment and structural bioinformatics analyses revealed that the catalytic residues (Cys51 and His148) are highly conserved in FMDV Lb<sup>pro</sup> of all seven serotypes and that the topology of FMDV Lb<sup>pro</sup> is remarkably similar to that of ubiquitin-specific protease 14 (USP14), a cellular deubiquitylation enzyme (DUB), and to that of severe acute respiratory syndrome coronavirus (SARS-CoV) papain-like protease (PLpro), a coronaviral DUB. Both purified Lb<sup>pro</sup> protein and in vivo ectopically expressed Lb<sup>pro</sup> removed ubiquitin (Ub) moieties from cellular substrates, acting on both lysine-48- and lysine-63-linked polyubiquitin chains. Furthermore, Lb<sup>pro</sup> significantly inhibited ubiquitination of retinoic acid-inducible gene I (RIG-I), TANK-binding kinase 1 (TBK1), TNF receptor-associated factor 6 (TRAF6), and TRAF3, key signaling molecules in activation of type I IFN response. Mutations in Lb<sup>pro</sup> that ablate the catalytic activity (C51A or D163N/D164N) or disrupt the SAP (for SAF-A/B, Acinus, and PIAS) domain (I83A/L86A) abrogated the DUB activity of Lb<sup>pro</sup> as well as its ability to block signaling to the IFN-β promoter. Collectively, these results demonstrate that FMDV Lb<sup>pro</sup> possesses DUB activity in addition to serving as a viral proteinase and describe a novel mechanism evolved by FMDV to counteract host innate antiviral responses.</div></front></TEI><affiliations><list><country><li>République populaire de Chine</li><li>États-Unis</li></country><region><li>Hubei</li></region><settlement><li>Pékin</li><li>Wuhan</li></settlement></list><tree><country name="République populaire de Chine"><region name="Hubei"><name sortKey="Dang Wang" sort="Dang Wang" uniqKey="Dang Wang" last="Dang Wang">DANG WANG</name></region><name sortKey="Huanchun Chen" sort="Huanchun Chen" uniqKey="Huanchun Chen" last="Huanchun Chen">HUANCHUN CHEN</name><name sortKey="Jinxiu Fan" sort="Jinxiu Fan" uniqKey="Jinxiu Fan" last="Jinxiu Fan">JINXIU FAN</name><name sortKey="Li Sun" sort="Li Sun" uniqKey="Li Sun" last="Li Sun">LI SUN</name><name sortKey="Liurong Fang" sort="Liurong Fang" uniqKey="Liurong Fang" last="Liurong Fang">LIURONG FANG</name><name sortKey="Ping Li" sort="Ping Li" uniqKey="Ping Li" last="Ping Li">PING LI</name><name sortKey="Qingye Zhang" sort="Qingye Zhang" uniqKey="Qingye Zhang" last="Qingye Zhang">QINGYE ZHANG</name><name sortKey="Rui Luo" sort="Rui Luo" uniqKey="Rui Luo" last="Rui Luo">RUI LUO</name><name sortKey="Shaobo Xiao" sort="Shaobo Xiao" uniqKey="Shaobo Xiao" last="Shaobo Xiao">SHAOBO XIAO</name><name sortKey="Xiangtao Liu" sort="Xiangtao Liu" uniqKey="Xiangtao Liu" last="Xiangtao Liu">XIANGTAO LIU</name><name sortKey="Zhongbin Chen" sort="Zhongbin Chen" uniqKey="Zhongbin Chen" last="Zhongbin Chen">ZHONGBIN CHEN</name></country><country name="États-Unis"><noRegion><name sortKey="Kui Li" sort="Kui Li" uniqKey="Kui Li" last="Kui Li">KUI LI</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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