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H5N1 Hybrid Viruses Bearing 2009/H1N1 Virus Genes Transmit in Guinea Pigs by Respiratory Droplet
In the past, avian influenza viruses have crossed species barriers to trigger human pandemics by reassorting with mammal-infective viruses in intermediate livestock hosts. H5N1 viruses are able to infect pigs, and some of them have affinity for the mammalian type α-2,6-linked sialic acid airway rece...
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Published in: | Science (American Association for the Advancement of Science) 2013-06, Vol.340 (6139), p.1459-1463 |
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creator | Zhang, Ying Zhang, Qianyi Kong, Huihui Jiang, Yongping Gao, Yuwei Deng, Guohua Shi, Jianzhong Tian, Guobin Liu, Liling Liu, Jinxiong Guan, Yuntao Bu, Zhigao Chen, Hualan |
description | In the past, avian influenza viruses have crossed species barriers to trigger human pandemics by reassorting with mammal-infective viruses in intermediate livestock hosts. H5N1 viruses are able to infect pigs, and some of them have affinity for the mammalian type α-2,6-linked sialic acid airway receptor. Using reverse genetics, we systematically created 127 reassortant viruses between a duck isolate of H5N1, specifically retaining its hemagglutinin (HA) gene throughout, and a highly transmissible, human-infective H1N1 virus. We tested the virulence of the reassortants in mice as a correlate for virulence in humans and tested transmissibility in guinea pigs, which have both avian and mammalian types of airway receptor. Transmission studies snowed that the H1N1 virus genes encoding acidic polymerase and nonstructural protein made the H5N1 virus transmissible by respiratory droplet between guinea pigs without killing them. Further experiments implicated other H1N1 genes in the enhancement of mammal-to-mammal transmission, including those that encode nucleoprotein, neuraminidase, and matrix, as well as mutations in H5 HA that improve affinity for humanlike airway receptors. Hence, avian H5N1 subtype viruses do have the potential to acquire mammalian transmissibility by reassortment in current agricultural scenarios. |
doi_str_mv | 10.1126/science.1229455 |
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H5N1 viruses are able to infect pigs, and some of them have affinity for the mammalian type α-2,6-linked sialic acid airway receptor. Using reverse genetics, we systematically created 127 reassortant viruses between a duck isolate of H5N1, specifically retaining its hemagglutinin (HA) gene throughout, and a highly transmissible, human-infective H1N1 virus. We tested the virulence of the reassortants in mice as a correlate for virulence in humans and tested transmissibility in guinea pigs, which have both avian and mammalian types of airway receptor. Transmission studies snowed that the H1N1 virus genes encoding acidic polymerase and nonstructural protein made the H5N1 virus transmissible by respiratory droplet between guinea pigs without killing them. Further experiments implicated other H1N1 genes in the enhancement of mammal-to-mammal transmission, including those that encode nucleoprotein, neuraminidase, and matrix, as well as mutations in H5 HA that improve affinity for humanlike airway receptors. Hence, avian H5N1 subtype viruses do have the potential to acquire mammalian transmissibility by reassortment in current agricultural scenarios.</description><identifier>ISSN: 0036-8075</identifier><identifier>EISSN: 1095-9203</identifier><identifier>DOI: 10.1126/science.1229455</identifier><identifier>PMID: 23641061</identifier><identifier>CODEN: SCIEAS</identifier><language>eng</language><publisher>United States: American Association for the Advancement of Science</publisher><subject>Amino Acid Sequence ; Animals ; Avian flu ; Brain - virology ; Cell Line ; Data transmission ; Disease transmission ; Epidemics ; Ferrets ; Genes ; Genes, Viral ; Guinea Pigs ; H5N1 subtype influenza A virus ; Hemagglutinin Glycoproteins, Influenza Virus - chemistry ; Hemagglutinin Glycoproteins, Influenza Virus - genetics ; Humans ; Influenza A Virus, H1N1 Subtype - genetics ; Influenza A Virus, H1N1 Subtype - pathogenicity ; Influenza A Virus, H5N1 Subtype - genetics ; Influenza A Virus, H5N1 Subtype - pathogenicity ; Influenza virus ; Influenza, Human - transmission ; Influenza, Human - virology ; Mice ; Mice, Inbred BALB C ; Molecular Sequence Data ; Mutation ; Neurons ; Orthomyxoviridae ; Orthomyxoviridae Infections - transmission ; Orthomyxoviridae Infections - virology ; Reassortant Viruses - genetics ; Reassortant Viruses - pathogenicity ; Receptors, Cell Surface - metabolism ; Receptors, Virus - metabolism ; Respiratory diseases ; Respiratory System - virology ; Reverse Genetics ; Ribonucleoproteins - metabolism ; Transmission efficiency ; Viral Proteins - genetics ; Viral Proteins - metabolism ; Virulence ; Virus Replication ; Viruses</subject><ispartof>Science (American Association for the Advancement of Science), 2013-06, Vol.340 (6139), p.1459-1463</ispartof><rights>Copyright © 2013 American Association for the Advancement of Science</rights><rights>Copyright © 2013, American Association for the Advancement of Science</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c487t-7f6ab8e1f570f9a4cf9b8ef1aca86eade743f9dea2159f6e28fe4c3be825da113</citedby><cites>FETCH-LOGICAL-c487t-7f6ab8e1f570f9a4cf9b8ef1aca86eade743f9dea2159f6e28fe4c3be825da113</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/41988744$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/41988744$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>315,786,790,2902,2903,27957,27958,58593,58826</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23641061$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhang, Ying</creatorcontrib><creatorcontrib>Zhang, Qianyi</creatorcontrib><creatorcontrib>Kong, Huihui</creatorcontrib><creatorcontrib>Jiang, Yongping</creatorcontrib><creatorcontrib>Gao, Yuwei</creatorcontrib><creatorcontrib>Deng, Guohua</creatorcontrib><creatorcontrib>Shi, Jianzhong</creatorcontrib><creatorcontrib>Tian, Guobin</creatorcontrib><creatorcontrib>Liu, Liling</creatorcontrib><creatorcontrib>Liu, Jinxiong</creatorcontrib><creatorcontrib>Guan, Yuntao</creatorcontrib><creatorcontrib>Bu, Zhigao</creatorcontrib><creatorcontrib>Chen, Hualan</creatorcontrib><title>H5N1 Hybrid Viruses Bearing 2009/H1N1 Virus Genes Transmit in Guinea Pigs by Respiratory Droplet</title><title>Science (American Association for the Advancement of Science)</title><addtitle>Science</addtitle><description>In the past, avian influenza viruses have crossed species barriers to trigger human pandemics by reassorting with mammal-infective viruses in intermediate livestock hosts. H5N1 viruses are able to infect pigs, and some of them have affinity for the mammalian type α-2,6-linked sialic acid airway receptor. Using reverse genetics, we systematically created 127 reassortant viruses between a duck isolate of H5N1, specifically retaining its hemagglutinin (HA) gene throughout, and a highly transmissible, human-infective H1N1 virus. We tested the virulence of the reassortants in mice as a correlate for virulence in humans and tested transmissibility in guinea pigs, which have both avian and mammalian types of airway receptor. Transmission studies snowed that the H1N1 virus genes encoding acidic polymerase and nonstructural protein made the H5N1 virus transmissible by respiratory droplet between guinea pigs without killing them. Further experiments implicated other H1N1 genes in the enhancement of mammal-to-mammal transmission, including those that encode nucleoprotein, neuraminidase, and matrix, as well as mutations in H5 HA that improve affinity for humanlike airway receptors. Hence, avian H5N1 subtype viruses do have the potential to acquire mammalian transmissibility by reassortment in current agricultural scenarios.</description><subject>Amino Acid Sequence</subject><subject>Animals</subject><subject>Avian flu</subject><subject>Brain - virology</subject><subject>Cell Line</subject><subject>Data transmission</subject><subject>Disease transmission</subject><subject>Epidemics</subject><subject>Ferrets</subject><subject>Genes</subject><subject>Genes, Viral</subject><subject>Guinea Pigs</subject><subject>H5N1 subtype influenza A virus</subject><subject>Hemagglutinin Glycoproteins, Influenza Virus - chemistry</subject><subject>Hemagglutinin Glycoproteins, Influenza Virus - genetics</subject><subject>Humans</subject><subject>Influenza A Virus, H1N1 Subtype - genetics</subject><subject>Influenza A Virus, H1N1 Subtype - pathogenicity</subject><subject>Influenza A Virus, H5N1 Subtype - genetics</subject><subject>Influenza A Virus, H5N1 Subtype - pathogenicity</subject><subject>Influenza virus</subject><subject>Influenza, Human - transmission</subject><subject>Influenza, Human - virology</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Molecular Sequence Data</subject><subject>Mutation</subject><subject>Neurons</subject><subject>Orthomyxoviridae</subject><subject>Orthomyxoviridae Infections - transmission</subject><subject>Orthomyxoviridae Infections - virology</subject><subject>Reassortant Viruses - genetics</subject><subject>Reassortant Viruses - pathogenicity</subject><subject>Receptors, Cell Surface - metabolism</subject><subject>Receptors, Virus - metabolism</subject><subject>Respiratory diseases</subject><subject>Respiratory System - virology</subject><subject>Reverse Genetics</subject><subject>Ribonucleoproteins - metabolism</subject><subject>Transmission efficiency</subject><subject>Viral Proteins - genetics</subject><subject>Viral Proteins - metabolism</subject><subject>Virulence</subject><subject>Virus Replication</subject><subject>Viruses</subject><issn>0036-8075</issn><issn>1095-9203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><recordid>eNqFkc1PGzEQxa2qqIS0555Alrj0ssTjz_WxQEmQEFRV2uvWuztGjpLdYO8e8t9jSMqhF06j0fvNk-Y9Qr4CuwDgepaagF2DF8C5lUp9IBNgVhWWM_GRTBgTuiiZUcfkJKUVY1mz4hM55kJLYBom5O9C3QNd7OoYWvonxDFhopfoYugeKc8HswVk4FWhc-yyuoyuS5sw0NDR-Rg6dPRneEy03tFfmLYhuqGPO3od--0ah8_kyLt1wi-HOSW_b34srxbF3cP89ur7XdHI0gyF8drVJYJXhnnrZONtXj24xpUaXYtGCm9bdByU9Rp56VE2osaSq9YBiCn5tvfdxv5pxDRUm5AaXK9dh_2YKlAKtADJ9PuoMJnKeb64nv-HrvoxdvmRVwq0AWsyNdtTTexTiuirbQwbF3cVsOqlp-rQU3XoKV-cHXzHeoPtG_-vmAyc7oFVymm-6RJsWRopxTMmnJcr</recordid><startdate>20130621</startdate><enddate>20130621</enddate><creator>Zhang, Ying</creator><creator>Zhang, Qianyi</creator><creator>Kong, Huihui</creator><creator>Jiang, Yongping</creator><creator>Gao, Yuwei</creator><creator>Deng, Guohua</creator><creator>Shi, Jianzhong</creator><creator>Tian, Guobin</creator><creator>Liu, Liling</creator><creator>Liu, Jinxiong</creator><creator>Guan, Yuntao</creator><creator>Bu, Zhigao</creator><creator>Chen, Hualan</creator><general>American Association for the Advancement of Science</general><general>The American Association for the Advancement of Science</general><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>7QF</scope><scope>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QQ</scope><scope>7QR</scope><scope>7SC</scope><scope>7SE</scope><scope>7SN</scope><scope>7SP</scope><scope>7SR</scope><scope>7SS</scope><scope>7T7</scope><scope>7TA</scope><scope>7TB</scope><scope>7TK</scope><scope>7TM</scope><scope>7U5</scope><scope>7U9</scope><scope>8BQ</scope><scope>8FD</scope><scope>C1K</scope><scope>F28</scope><scope>FR3</scope><scope>H8D</scope><scope>H8G</scope><scope>H94</scope><scope>JG9</scope><scope>JQ2</scope><scope>K9.</scope><scope>KR7</scope><scope>L7M</scope><scope>L~C</scope><scope>L~D</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20130621</creationdate><title>H5N1 Hybrid Viruses Bearing 2009/H1N1 Virus Genes Transmit in Guinea Pigs by Respiratory Droplet</title><author>Zhang, Ying ; Zhang, Qianyi ; Kong, Huihui ; Jiang, Yongping ; Gao, Yuwei ; Deng, Guohua ; Shi, Jianzhong ; Tian, Guobin ; Liu, Liling ; Liu, Jinxiong ; Guan, Yuntao ; Bu, Zhigao ; Chen, Hualan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c487t-7f6ab8e1f570f9a4cf9b8ef1aca86eade743f9dea2159f6e28fe4c3be825da113</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Amino Acid Sequence</topic><topic>Animals</topic><topic>Avian flu</topic><topic>Brain - virology</topic><topic>Cell Line</topic><topic>Data transmission</topic><topic>Disease transmission</topic><topic>Epidemics</topic><topic>Ferrets</topic><topic>Genes</topic><topic>Genes, Viral</topic><topic>Guinea Pigs</topic><topic>H5N1 subtype influenza A virus</topic><topic>Hemagglutinin Glycoproteins, Influenza Virus - chemistry</topic><topic>Hemagglutinin Glycoproteins, Influenza Virus - genetics</topic><topic>Humans</topic><topic>Influenza A Virus, H1N1 Subtype - genetics</topic><topic>Influenza A Virus, H1N1 Subtype - pathogenicity</topic><topic>Influenza A Virus, H5N1 Subtype - genetics</topic><topic>Influenza A Virus, H5N1 Subtype - pathogenicity</topic><topic>Influenza virus</topic><topic>Influenza, Human - transmission</topic><topic>Influenza, Human - virology</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Molecular Sequence Data</topic><topic>Mutation</topic><topic>Neurons</topic><topic>Orthomyxoviridae</topic><topic>Orthomyxoviridae Infections - transmission</topic><topic>Orthomyxoviridae Infections - 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Academic</collection><jtitle>Science (American Association for the Advancement of Science)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhang, Ying</au><au>Zhang, Qianyi</au><au>Kong, Huihui</au><au>Jiang, Yongping</au><au>Gao, Yuwei</au><au>Deng, Guohua</au><au>Shi, Jianzhong</au><au>Tian, Guobin</au><au>Liu, Liling</au><au>Liu, Jinxiong</au><au>Guan, Yuntao</au><au>Bu, Zhigao</au><au>Chen, Hualan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>H5N1 Hybrid Viruses Bearing 2009/H1N1 Virus Genes Transmit in Guinea Pigs by Respiratory Droplet</atitle><jtitle>Science (American Association for the Advancement of Science)</jtitle><addtitle>Science</addtitle><date>2013-06-21</date><risdate>2013</risdate><volume>340</volume><issue>6139</issue><spage>1459</spage><epage>1463</epage><pages>1459-1463</pages><issn>0036-8075</issn><eissn>1095-9203</eissn><coden>SCIEAS</coden><notes>ObjectType-Article-1</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-2</notes><notes>content type line 23</notes><abstract>In the past, avian influenza viruses have crossed species barriers to trigger human pandemics by reassorting with mammal-infective viruses in intermediate livestock hosts. H5N1 viruses are able to infect pigs, and some of them have affinity for the mammalian type α-2,6-linked sialic acid airway receptor. Using reverse genetics, we systematically created 127 reassortant viruses between a duck isolate of H5N1, specifically retaining its hemagglutinin (HA) gene throughout, and a highly transmissible, human-infective H1N1 virus. We tested the virulence of the reassortants in mice as a correlate for virulence in humans and tested transmissibility in guinea pigs, which have both avian and mammalian types of airway receptor. Transmission studies snowed that the H1N1 virus genes encoding acidic polymerase and nonstructural protein made the H5N1 virus transmissible by respiratory droplet between guinea pigs without killing them. Further experiments implicated other H1N1 genes in the enhancement of mammal-to-mammal transmission, including those that encode nucleoprotein, neuraminidase, and matrix, as well as mutations in H5 HA that improve affinity for humanlike airway receptors. Hence, avian H5N1 subtype viruses do have the potential to acquire mammalian transmissibility by reassortment in current agricultural scenarios.</abstract><cop>United States</cop><pub>American Association for the Advancement of Science</pub><pmid>23641061</pmid><doi>10.1126/science.1229455</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Amino Acid Sequence Animals Avian flu Brain - virology Cell Line Data transmission Disease transmission Epidemics Ferrets Genes Genes, Viral Guinea Pigs H5N1 subtype influenza A virus Hemagglutinin Glycoproteins, Influenza Virus - chemistry Hemagglutinin Glycoproteins, Influenza Virus - genetics Humans Influenza A Virus, H1N1 Subtype - genetics Influenza A Virus, H1N1 Subtype - pathogenicity Influenza A Virus, H5N1 Subtype - genetics Influenza A Virus, H5N1 Subtype - pathogenicity Influenza virus Influenza, Human - transmission Influenza, Human - virology Mice Mice, Inbred BALB C Molecular Sequence Data Mutation Neurons Orthomyxoviridae Orthomyxoviridae Infections - transmission Orthomyxoviridae Infections - virology Reassortant Viruses - genetics Reassortant Viruses - pathogenicity Receptors, Cell Surface - metabolism Receptors, Virus - metabolism Respiratory diseases Respiratory System - virology Reverse Genetics Ribonucleoproteins - metabolism Transmission efficiency Viral Proteins - genetics Viral Proteins - metabolism Virulence Virus Replication Viruses |
title | H5N1 Hybrid Viruses Bearing 2009/H1N1 Virus Genes Transmit in Guinea Pigs by Respiratory Droplet |
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