Effect on Virulence and Pathogenicity of H5N1 Influenza A Virus through Truncations of NS1 eIF4GI Binding Domain
To study the effect of NS1 eIF4GI binding domain on virulence and pathogenicity of H5N1 influenza A virus, 5 recombinant H5N1 viruses encoding eIF4GI binding domain—truncated NS1 proteins and parental NS1 (NS1-wt) were generated by an 8-plasmid—based reverse genetics system. The results indicated th...
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| Veröffentlicht in: | The Journal of infectious diseases 2010-11, Vol.202 (9), p.1338-1346 |
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| container_title | The Journal of infectious diseases |
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| creator | Zhou, Hongbo Zhu, Jiping Tu, Jiagang Zou, Wei Hu, Yong Yu, Zhengjun Yin, Wensi Li, Yongtao Zhang, Anding Wu, Yurong Yu, Ziniu Chen, Huanchun Jin, Meilin |
| description | To study the effect of NS1 eIF4GI binding domain on virulence and pathogenicity of H5N1 influenza A virus, 5 recombinant H5N1 viruses encoding eIF4GI binding domain—truncated NS1 proteins and parental NS1 (NS1-wt) were generated by an 8-plasmid—based reverse genetics system. The results indicated that the recombinants with the addition of 5-amino acid and the deletion position of 85–89 in NS1-wt were attenuated in replication in vitro and in vivo, compared with the recombinant wild-type virus rNS1-wt, whereas the deletion position 85–94 or the entire eIF4GI binding domain in NS1-wt displayed a significantly attenuated phenotype in chicken and mice. We also showed that the eIF4GI binding domain—truncated mutants were impaired in their ability to inhibit interferon production in vitro, and they did not replicate as efficiently as the parental recombinant strain in embryonated hen eggs, in Madin-Darby Canine Kidney cells, or in vivo in chickens and in a mouse model. Therefore, these attenuated NS1-truncated viruses may have a great potential as live attenuated vaccine candidates against H5N1 influenza A virus. |
| doi_str_mv | 10.1086/656536 |
| format | Article |
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The results indicated that the recombinants with the addition of 5-amino acid and the deletion position of 85–89 in NS1-wt were attenuated in replication in vitro and in vivo, compared with the recombinant wild-type virus rNS1-wt, whereas the deletion position 85–94 or the entire eIF4GI binding domain in NS1-wt displayed a significantly attenuated phenotype in chicken and mice. We also showed that the eIF4GI binding domain—truncated mutants were impaired in their ability to inhibit interferon production in vitro, and they did not replicate as efficiently as the parental recombinant strain in embryonated hen eggs, in Madin-Darby Canine Kidney cells, or in vivo in chickens and in a mouse model. Therefore, these attenuated NS1-truncated viruses may have a great potential as live attenuated vaccine candidates against H5N1 influenza A virus.</description><identifier>ISSN: 0022-1899</identifier><identifier>EISSN: 1537-6613</identifier><identifier>DOI: 10.1086/656536</identifier><identifier>PMID: 20854176</identifier><identifier>CODEN: JIDIAQ</identifier><language>eng</language><publisher>Oxford: The University of Chicago Press</publisher><subject>Animals ; Biological and medical sciences ; Cell Line ; Chick Embryo ; Chickens ; Dogs ; Eukaryotic Initiation Factor-4G - metabolism ; Female ; Fundamental and applied biological sciences. Psychology ; H5N1 subtype influenza A virus ; Infections ; Infectious diseases ; Influenza A virus ; Influenza A Virus, H5N1 Subtype - genetics ; Influenza A Virus, H5N1 Subtype - pathogenicity ; Influenza in Birds - pathology ; Influenza in Birds - virology ; Interferons - antagonists & inhibitors ; Interferons - immunology ; Medical sciences ; Messenger RNA ; Mice ; Mice, Inbred BALB C ; Microbiology ; Orthomyxoviridae ; Orthomyxoviridae Infections - pathology ; Orthomyxoviridae Infections - virology ; Protein Binding ; Sequence Deletion ; Transcriptional regulatory elements ; Vero cells ; Viral Nonstructural Proteins - genetics ; Viral Nonstructural Proteins - metabolism ; Virulence ; Virulence Factors - genetics ; Virulence Factors - metabolism ; Virus Replication ; Viruses</subject><ispartof>The Journal of infectious diseases, 2010-11, Vol.202 (9), p.1338-1346</ispartof><rights>2010 Infectious Diseases Society of America</rights><rights>2010 by the Infectious Diseases Society of America 2010</rights><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c459t-9d1cb745c67650026e799f67794873f365cf3907500dc04ce0beb3a06dfcc27c3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/20790067$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/20790067$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>314,780,784,803,27924,27925,58017,58250</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=23324773$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20854176$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhou, Hongbo</creatorcontrib><creatorcontrib>Zhu, Jiping</creatorcontrib><creatorcontrib>Tu, Jiagang</creatorcontrib><creatorcontrib>Zou, Wei</creatorcontrib><creatorcontrib>Hu, Yong</creatorcontrib><creatorcontrib>Yu, Zhengjun</creatorcontrib><creatorcontrib>Yin, Wensi</creatorcontrib><creatorcontrib>Li, Yongtao</creatorcontrib><creatorcontrib>Zhang, Anding</creatorcontrib><creatorcontrib>Wu, Yurong</creatorcontrib><creatorcontrib>Yu, Ziniu</creatorcontrib><creatorcontrib>Chen, Huanchun</creatorcontrib><creatorcontrib>Jin, Meilin</creatorcontrib><title>Effect on Virulence and Pathogenicity of H5N1 Influenza A Virus through Truncations of NS1 eIF4GI Binding Domain</title><title>The Journal of infectious diseases</title><addtitle>J Infect Dis</addtitle><addtitle>J Infect Dis</addtitle><description>To study the effect of NS1 eIF4GI binding domain on virulence and pathogenicity of H5N1 influenza A virus, 5 recombinant H5N1 viruses encoding eIF4GI binding domain—truncated NS1 proteins and parental NS1 (NS1-wt) were generated by an 8-plasmid—based reverse genetics system. The results indicated that the recombinants with the addition of 5-amino acid and the deletion position of 85–89 in NS1-wt were attenuated in replication in vitro and in vivo, compared with the recombinant wild-type virus rNS1-wt, whereas the deletion position 85–94 or the entire eIF4GI binding domain in NS1-wt displayed a significantly attenuated phenotype in chicken and mice. We also showed that the eIF4GI binding domain—truncated mutants were impaired in their ability to inhibit interferon production in vitro, and they did not replicate as efficiently as the parental recombinant strain in embryonated hen eggs, in Madin-Darby Canine Kidney cells, or in vivo in chickens and in a mouse model. Therefore, these attenuated NS1-truncated viruses may have a great potential as live attenuated vaccine candidates against H5N1 influenza A virus.</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Cell Line</subject><subject>Chick Embryo</subject><subject>Chickens</subject><subject>Dogs</subject><subject>Eukaryotic Initiation Factor-4G - metabolism</subject><subject>Female</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>H5N1 subtype influenza A virus</subject><subject>Infections</subject><subject>Infectious diseases</subject><subject>Influenza A virus</subject><subject>Influenza A Virus, H5N1 Subtype - genetics</subject><subject>Influenza A Virus, H5N1 Subtype - pathogenicity</subject><subject>Influenza in Birds - pathology</subject><subject>Influenza in Birds - virology</subject><subject>Interferons - antagonists & inhibitors</subject><subject>Interferons - immunology</subject><subject>Medical sciences</subject><subject>Messenger RNA</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Microbiology</subject><subject>Orthomyxoviridae</subject><subject>Orthomyxoviridae Infections - pathology</subject><subject>Orthomyxoviridae Infections - virology</subject><subject>Protein Binding</subject><subject>Sequence Deletion</subject><subject>Transcriptional regulatory elements</subject><subject>Vero cells</subject><subject>Viral Nonstructural Proteins - genetics</subject><subject>Viral Nonstructural Proteins - metabolism</subject><subject>Virulence</subject><subject>Virulence Factors - genetics</subject><subject>Virulence Factors - metabolism</subject><subject>Virus Replication</subject><subject>Viruses</subject><issn>0022-1899</issn><issn>1537-6613</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp90UtvEzEQB3ALgWho4RuAzIHHZcFev9bHUtokalVeBaFeVo7XTtxu7GB7Jcqnx2XTlguc5vD_aUYzA8ATjN5g1PC3nHFG-D0wwYyIinNM7oMJQnVd4UbKHfAopQuEECVcPAQ7NWoYxYJPwObQWqMzDB5-c3HojdcGKt_BjyqvwtJ4p12-gsHCGTvFcO5tPxj_S8H9Pz7BvIphWK7gWRy8VtkFn6716RcMzfyITufwnfOd80v4PqyV83vggVV9Mo-3dRd8PTo8O5hVJx-m84P9k0pTJnMlO6wXgjLNBWdlD26ElJYLIWkjiCWcaUskEiXrNKLaoIVZEIV4Z7WuhSa74NXYdxPDj8Gk3K5d0qbvlTdhSK1gvFwJI1bk6_9KjDBFsiG4KfTlSHUMKUVj2010axWvCmqv_9COfyjw2bbnsFib7pbdHL6AF1ugkla9jcprl-4cITUVghT3fHRh2Px72NPRXKQc4l-zhESIi5JXY-5SNj9vcxUv25IK1s6-n7fH9Jx_-jzFbUN-A-y6rws</recordid><startdate>20101101</startdate><enddate>20101101</enddate><creator>Zhou, Hongbo</creator><creator>Zhu, Jiping</creator><creator>Tu, Jiagang</creator><creator>Zou, Wei</creator><creator>Hu, Yong</creator><creator>Yu, Zhengjun</creator><creator>Yin, Wensi</creator><creator>Li, Yongtao</creator><creator>Zhang, Anding</creator><creator>Wu, Yurong</creator><creator>Yu, Ziniu</creator><creator>Chen, Huanchun</creator><creator>Jin, Meilin</creator><general>The University of Chicago Press</general><general>University of Chicago Press</general><general>Oxford University Press</general><scope>BSCLL</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7U9</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>20101101</creationdate><title>Effect on Virulence and Pathogenicity of H5N1 Influenza A Virus through Truncations of NS1 eIF4GI Binding Domain</title><author>Zhou, Hongbo ; Zhu, Jiping ; Tu, Jiagang ; Zou, Wei ; Hu, Yong ; Yu, Zhengjun ; Yin, Wensi ; Li, Yongtao ; Zhang, Anding ; Wu, Yurong ; Yu, Ziniu ; Chen, Huanchun ; Jin, Meilin</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c459t-9d1cb745c67650026e799f67794873f365cf3907500dc04ce0beb3a06dfcc27c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Cell Line</topic><topic>Chick Embryo</topic><topic>Chickens</topic><topic>Dogs</topic><topic>Eukaryotic Initiation Factor-4G - metabolism</topic><topic>Female</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>H5N1 subtype influenza A virus</topic><topic>Infections</topic><topic>Infectious diseases</topic><topic>Influenza A virus</topic><topic>Influenza A Virus, H5N1 Subtype - genetics</topic><topic>Influenza A Virus, H5N1 Subtype - pathogenicity</topic><topic>Influenza in Birds - pathology</topic><topic>Influenza in Birds - virology</topic><topic>Interferons - antagonists & inhibitors</topic><topic>Interferons - immunology</topic><topic>Medical sciences</topic><topic>Messenger RNA</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Microbiology</topic><topic>Orthomyxoviridae</topic><topic>Orthomyxoviridae Infections - pathology</topic><topic>Orthomyxoviridae Infections - virology</topic><topic>Protein Binding</topic><topic>Sequence Deletion</topic><topic>Transcriptional regulatory elements</topic><topic>Vero cells</topic><topic>Viral Nonstructural Proteins - genetics</topic><topic>Viral Nonstructural Proteins - metabolism</topic><topic>Virulence</topic><topic>Virulence Factors - genetics</topic><topic>Virulence Factors - metabolism</topic><topic>Virus Replication</topic><topic>Viruses</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhou, Hongbo</creatorcontrib><creatorcontrib>Zhu, Jiping</creatorcontrib><creatorcontrib>Tu, Jiagang</creatorcontrib><creatorcontrib>Zou, Wei</creatorcontrib><creatorcontrib>Hu, Yong</creatorcontrib><creatorcontrib>Yu, Zhengjun</creatorcontrib><creatorcontrib>Yin, Wensi</creatorcontrib><creatorcontrib>Li, Yongtao</creatorcontrib><creatorcontrib>Zhang, Anding</creatorcontrib><creatorcontrib>Wu, Yurong</creatorcontrib><creatorcontrib>Yu, Ziniu</creatorcontrib><creatorcontrib>Chen, Huanchun</creatorcontrib><creatorcontrib>Jin, Meilin</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>The Journal of infectious diseases</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhou, Hongbo</au><au>Zhu, Jiping</au><au>Tu, Jiagang</au><au>Zou, Wei</au><au>Hu, Yong</au><au>Yu, Zhengjun</au><au>Yin, Wensi</au><au>Li, Yongtao</au><au>Zhang, Anding</au><au>Wu, Yurong</au><au>Yu, Ziniu</au><au>Chen, Huanchun</au><au>Jin, Meilin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effect on Virulence and Pathogenicity of H5N1 Influenza A Virus through Truncations of NS1 eIF4GI Binding Domain</atitle><jtitle>The Journal of infectious diseases</jtitle><stitle>J Infect Dis</stitle><addtitle>J Infect Dis</addtitle><date>2010-11-01</date><risdate>2010</risdate><volume>202</volume><issue>9</issue><spage>1338</spage><epage>1346</epage><pages>1338-1346</pages><issn>0022-1899</issn><eissn>1537-6613</eissn><coden>JIDIAQ</coden><abstract>To study the effect of NS1 eIF4GI binding domain on virulence and pathogenicity of H5N1 influenza A virus, 5 recombinant H5N1 viruses encoding eIF4GI binding domain—truncated NS1 proteins and parental NS1 (NS1-wt) were generated by an 8-plasmid—based reverse genetics system. The results indicated that the recombinants with the addition of 5-amino acid and the deletion position of 85–89 in NS1-wt were attenuated in replication in vitro and in vivo, compared with the recombinant wild-type virus rNS1-wt, whereas the deletion position 85–94 or the entire eIF4GI binding domain in NS1-wt displayed a significantly attenuated phenotype in chicken and mice. We also showed that the eIF4GI binding domain—truncated mutants were impaired in their ability to inhibit interferon production in vitro, and they did not replicate as efficiently as the parental recombinant strain in embryonated hen eggs, in Madin-Darby Canine Kidney cells, or in vivo in chickens and in a mouse model. Therefore, these attenuated NS1-truncated viruses may have a great potential as live attenuated vaccine candidates against H5N1 influenza A virus.</abstract><cop>Oxford</cop><pub>The University of Chicago Press</pub><pmid>20854176</pmid><doi>10.1086/656536</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Biological and medical sciences Cell Line Chick Embryo Chickens Dogs Eukaryotic Initiation Factor-4G - metabolism Female Fundamental and applied biological sciences. Psychology H5N1 subtype influenza A virus Infections Infectious diseases Influenza A virus Influenza A Virus, H5N1 Subtype - genetics Influenza A Virus, H5N1 Subtype - pathogenicity Influenza in Birds - pathology Influenza in Birds - virology Interferons - antagonists & inhibitors Interferons - immunology Medical sciences Messenger RNA Mice Mice, Inbred BALB C Microbiology Orthomyxoviridae Orthomyxoviridae Infections - pathology Orthomyxoviridae Infections - virology Protein Binding Sequence Deletion Transcriptional regulatory elements Vero cells Viral Nonstructural Proteins - genetics Viral Nonstructural Proteins - metabolism Virulence Virulence Factors - genetics Virulence Factors - metabolism Virus Replication Viruses |
| title | Effect on Virulence and Pathogenicity of H5N1 Influenza A Virus through Truncations of NS1 eIF4GI Binding Domain |
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