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Novel Highly Pathogenic Avian A(H5N2) and A(H5N8) Influenza Viruses of Clade 2.3.4.4 from North America Have Limited Capacity for Replication and Transmission in Mammals
Highly pathogenic influenza A(H5N8) viruses from clade 2.3.4.4 were introduced to North America by migratory birds in the fall of 2014. Reassortment of A(H5N8) viruses with avian viruses of North American lineage resulted in the generation of novel A(H5N2) viruses with novel genotypes. Through seque...
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creator | Kaplan, Bryan S Russier, Marion Jeevan, Trushar Marathe, Bindumadhav Govorkova, Elena A Russell, Charles J Kim-Torchetti, Mia Choi, Young Ki Brown, Ian Saito, Takehiko Stallknecht, David E Krauss, Scott Webby, Richard J |
description | Highly pathogenic influenza A(H5N8) viruses from clade 2.3.4.4 were introduced to North America by migratory birds in the fall of 2014. Reassortment of A(H5N8) viruses with avian viruses of North American lineage resulted in the generation of novel A(H5N2) viruses with novel genotypes. Through sequencing of recent avian influenza viruses, we identified PB1 and NP gene segments very similar to those in the viruses isolated from North American waterfowl prior to the introduction of A(H5N8) to North America, highlighting these bird species in the origin of reassortant A(H5N2) viruses. While they were highly virulent and transmissible in poultry, we found A(H5N2) viruses to be low pathogenic in mice and ferrets, and replication was limited in both hosts compared with those of recent highly pathogenic avian influenza (HPAI) H5N1 viruses. Molecular characterization of the hemagglutinin protein from A(H5N2) viruses showed that the receptor binding preference, cleavage, and pH of activation were highly adapted for replication in avian species and similar to those of other 2.3.4.4 viruses. In addition, North American and Eurasian clade 2.3.4.4 H5NX viruses replicated to significantly lower titers in differentiated normal human bronchial epithelial cells than did seasonal human A(H1N1) and highly pathogenic A(H5N1) viruses isolated from a human case. Thus, despite their having a high impact on poultry, our findings suggest that the recently emerging North American A(H5N2) viruses are not expected to pose a substantial threat to humans and other mammals without further reassortment and/or adaptation and that reassortment with North American viruses has not had a major impact on viral phenotype. IMPORTANCE Highly pathogenic H5 influenza viruses have been introduced into North America from Asia, causing extensive morbidity and mortality in domestic poultry. The introduced viruses have reassorted with North American avian influenza viruses, generating viral genotypes not seen on other continents. The experiments and analyses presented here were designed to assess the impact of this genetic diversification on viral phenotypes, particularly as regards mammalian hosts, by comparing the North American viruses with their Eurasian precursor viruses. |
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Reassortment of A(H5N8) viruses with avian viruses of North American lineage resulted in the generation of novel A(H5N2) viruses with novel genotypes. Through sequencing of recent avian influenza viruses, we identified PB1 and NP gene segments very similar to those in the viruses isolated from North American waterfowl prior to the introduction of A(H5N8) to North America, highlighting these bird species in the origin of reassortant A(H5N2) viruses. While they were highly virulent and transmissible in poultry, we found A(H5N2) viruses to be low pathogenic in mice and ferrets, and replication was limited in both hosts compared with those of recent highly pathogenic avian influenza (HPAI) H5N1 viruses. Molecular characterization of the hemagglutinin protein from A(H5N2) viruses showed that the receptor binding preference, cleavage, and pH of activation were highly adapted for replication in avian species and similar to those of other 2.3.4.4 viruses. In addition, North American and Eurasian clade 2.3.4.4 H5NX viruses replicated to significantly lower titers in differentiated normal human bronchial epithelial cells than did seasonal human A(H1N1) and highly pathogenic A(H5N1) viruses isolated from a human case. Thus, despite their having a high impact on poultry, our findings suggest that the recently emerging North American A(H5N2) viruses are not expected to pose a substantial threat to humans and other mammals without further reassortment and/or adaptation and that reassortment with North American viruses has not had a major impact on viral phenotype. IMPORTANCE Highly pathogenic H5 influenza viruses have been introduced into North America from Asia, causing extensive morbidity and mortality in domestic poultry. The introduced viruses have reassorted with North American avian influenza viruses, generating viral genotypes not seen on other continents. The experiments and analyses presented here were designed to assess the impact of this genetic diversification on viral phenotypes, particularly as regards mammalian hosts, by comparing the North American viruses with their Eurasian precursor viruses.</description><identifier>ISSN: 2379-5042</identifier><identifier>EISSN: 2379-5042</identifier><identifier>DOI: 10.1128/mSphere.00003-16</identifier><identifier>PMID: 27303732</identifier><language>eng</language><publisher>United States: American Society for Microbiology</publisher><subject>avian influenza virus ; H5N2 ; H5N8 ; Hemagglutinins ; Influenza A ; mammals ; Migratory birds ; viral replication</subject><ispartof>mSphere, 2016-03, Vol.1 (2)</ispartof><rights>Copyright © 2016 Kaplan et al. This work is licensed under the Creative Commons Attribution License (https://creativecommons.org/licenses/by/3.0/) (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>Copyright © 2016 Kaplan et al. 2016 Kaplan et al.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c556t-7d2069bd477a71379c81b3f91bd83e8179161c1f2576b08eed9ed09dff3744473</citedby><cites>FETCH-LOGICAL-c556t-7d2069bd477a71379c81b3f91bd83e8179161c1f2576b08eed9ed09dff3744473</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/1953486460/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/1953486460?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,3175,25731,27901,27902,36989,36990,44566,53766,53768,74869</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27303732$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kaplan, Bryan S</creatorcontrib><creatorcontrib>Russier, Marion</creatorcontrib><creatorcontrib>Jeevan, Trushar</creatorcontrib><creatorcontrib>Marathe, Bindumadhav</creatorcontrib><creatorcontrib>Govorkova, Elena A</creatorcontrib><creatorcontrib>Russell, Charles J</creatorcontrib><creatorcontrib>Kim-Torchetti, Mia</creatorcontrib><creatorcontrib>Choi, Young Ki</creatorcontrib><creatorcontrib>Brown, Ian</creatorcontrib><creatorcontrib>Saito, Takehiko</creatorcontrib><creatorcontrib>Stallknecht, David E</creatorcontrib><creatorcontrib>Krauss, Scott</creatorcontrib><creatorcontrib>Webby, Richard J</creatorcontrib><title>Novel Highly Pathogenic Avian A(H5N2) and A(H5N8) Influenza Viruses of Clade 2.3.4.4 from North America Have Limited Capacity for Replication and Transmission in Mammals</title><title>mSphere</title><addtitle>mSphere</addtitle><description>Highly pathogenic influenza A(H5N8) viruses from clade 2.3.4.4 were introduced to North America by migratory birds in the fall of 2014. 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In addition, North American and Eurasian clade 2.3.4.4 H5NX viruses replicated to significantly lower titers in differentiated normal human bronchial epithelial cells than did seasonal human A(H1N1) and highly pathogenic A(H5N1) viruses isolated from a human case. Thus, despite their having a high impact on poultry, our findings suggest that the recently emerging North American A(H5N2) viruses are not expected to pose a substantial threat to humans and other mammals without further reassortment and/or adaptation and that reassortment with North American viruses has not had a major impact on viral phenotype. IMPORTANCE Highly pathogenic H5 influenza viruses have been introduced into North America from Asia, causing extensive morbidity and mortality in domestic poultry. The introduced viruses have reassorted with North American avian influenza viruses, generating viral genotypes not seen on other continents. The experiments and analyses presented here were designed to assess the impact of this genetic diversification on viral phenotypes, particularly as regards mammalian hosts, by comparing the North American viruses with their Eurasian precursor viruses.</description><subject>avian influenza virus</subject><subject>H5N2</subject><subject>H5N8</subject><subject>Hemagglutinins</subject><subject>Influenza A</subject><subject>mammals</subject><subject>Migratory birds</subject><subject>viral replication</subject><issn>2379-5042</issn><issn>2379-5042</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNpdkk1vEzEQhlcIRKvSOydkiUt7SFh_rL2-IEURkEghIChcLe96nLjatYO9iRT-Ef8S54OqxZcZjd957Bm9RfEal2OMSf2u_75ZQ4RxmQ8dYf6suCRUyFFVMvL8UX5RXKd0n0WYE84Ff1lcEEFLKii5LP4sww46NHOrdbdHX_WwDivwrkWTndMeTW5m1ZLcIu3NKa9v0dzbbgv-t0Y_XdwmSChYNO20AUTGdMzGDNkYerQMcVijSQ_RtRrN9A7QwvVuAIOmeqNbN-yRDRF9g02XFYML_vjOXdQ-9S6lQ8F59Fn3ve7Sq-KFzQGuz_Gq-PHxw910Nlp8-TSfThajtqr4MBKGlFw2hgmhBc47aGvcUCtxY2oKNRYSc9xiSyrBm7IGMBJMKY21VDDGBL0q5ieuCfpebaLrddyroJ06FkJcKR0H13agMk_LxjIiMWFNLWpTNoJby4C3zNR1Zr0_sTbbpgfTgh-i7p5An954t1arsFOslozLMgNuzoAYfm0hDSovpoWu0x7CNqk8jqgYFZXM0rf_Se_DNvq8KoVlRVnNGT8Ay5OqjSGlCPbhM7hUB1ups63U0VYK89zy5vEQDw3_TET_AjO-yCM</recordid><startdate>20160301</startdate><enddate>20160301</enddate><creator>Kaplan, Bryan S</creator><creator>Russier, Marion</creator><creator>Jeevan, Trushar</creator><creator>Marathe, Bindumadhav</creator><creator>Govorkova, Elena A</creator><creator>Russell, Charles J</creator><creator>Kim-Torchetti, Mia</creator><creator>Choi, Young Ki</creator><creator>Brown, Ian</creator><creator>Saito, Takehiko</creator><creator>Stallknecht, David E</creator><creator>Krauss, Scott</creator><creator>Webby, Richard J</creator><general>American Society for Microbiology</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20160301</creationdate><title>Novel Highly Pathogenic Avian A(H5N2) and A(H5N8) Influenza Viruses of Clade 2.3.4.4 from North America Have Limited Capacity for Replication and Transmission in Mammals</title><author>Kaplan, Bryan S ; Russier, Marion ; Jeevan, Trushar ; Marathe, Bindumadhav ; Govorkova, Elena A ; Russell, Charles J ; Kim-Torchetti, Mia ; Choi, Young Ki ; Brown, Ian ; Saito, Takehiko ; Stallknecht, David E ; Krauss, Scott ; Webby, Richard J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c556t-7d2069bd477a71379c81b3f91bd83e8179161c1f2576b08eed9ed09dff3744473</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>avian influenza virus</topic><topic>H5N2</topic><topic>H5N8</topic><topic>Hemagglutinins</topic><topic>Influenza A</topic><topic>mammals</topic><topic>Migratory birds</topic><topic>viral replication</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kaplan, Bryan S</creatorcontrib><creatorcontrib>Russier, Marion</creatorcontrib><creatorcontrib>Jeevan, Trushar</creatorcontrib><creatorcontrib>Marathe, Bindumadhav</creatorcontrib><creatorcontrib>Govorkova, Elena A</creatorcontrib><creatorcontrib>Russell, Charles J</creatorcontrib><creatorcontrib>Kim-Torchetti, Mia</creatorcontrib><creatorcontrib>Choi, Young Ki</creatorcontrib><creatorcontrib>Brown, Ian</creatorcontrib><creatorcontrib>Saito, Takehiko</creatorcontrib><creatorcontrib>Stallknecht, David E</creatorcontrib><creatorcontrib>Krauss, Scott</creatorcontrib><creatorcontrib>Webby, Richard J</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection (Proquest)</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>AUTh Library subscriptions: ProQuest Central</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biological Sciences</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Biological Science Database</collection><collection>Publicly Available Content (ProQuest)</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>mSphere</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kaplan, Bryan S</au><au>Russier, Marion</au><au>Jeevan, Trushar</au><au>Marathe, Bindumadhav</au><au>Govorkova, Elena A</au><au>Russell, Charles J</au><au>Kim-Torchetti, Mia</au><au>Choi, Young Ki</au><au>Brown, Ian</au><au>Saito, Takehiko</au><au>Stallknecht, David E</au><au>Krauss, Scott</au><au>Webby, Richard J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Novel Highly Pathogenic Avian A(H5N2) and A(H5N8) Influenza Viruses of Clade 2.3.4.4 from North America Have Limited Capacity for Replication and Transmission in Mammals</atitle><jtitle>mSphere</jtitle><addtitle>mSphere</addtitle><date>2016-03-01</date><risdate>2016</risdate><volume>1</volume><issue>2</issue><issn>2379-5042</issn><eissn>2379-5042</eissn><abstract>Highly pathogenic influenza A(H5N8) viruses from clade 2.3.4.4 were introduced to North America by migratory birds in the fall of 2014. Reassortment of A(H5N8) viruses with avian viruses of North American lineage resulted in the generation of novel A(H5N2) viruses with novel genotypes. Through sequencing of recent avian influenza viruses, we identified PB1 and NP gene segments very similar to those in the viruses isolated from North American waterfowl prior to the introduction of A(H5N8) to North America, highlighting these bird species in the origin of reassortant A(H5N2) viruses. While they were highly virulent and transmissible in poultry, we found A(H5N2) viruses to be low pathogenic in mice and ferrets, and replication was limited in both hosts compared with those of recent highly pathogenic avian influenza (HPAI) H5N1 viruses. Molecular characterization of the hemagglutinin protein from A(H5N2) viruses showed that the receptor binding preference, cleavage, and pH of activation were highly adapted for replication in avian species and similar to those of other 2.3.4.4 viruses. In addition, North American and Eurasian clade 2.3.4.4 H5NX viruses replicated to significantly lower titers in differentiated normal human bronchial epithelial cells than did seasonal human A(H1N1) and highly pathogenic A(H5N1) viruses isolated from a human case. Thus, despite their having a high impact on poultry, our findings suggest that the recently emerging North American A(H5N2) viruses are not expected to pose a substantial threat to humans and other mammals without further reassortment and/or adaptation and that reassortment with North American viruses has not had a major impact on viral phenotype. IMPORTANCE Highly pathogenic H5 influenza viruses have been introduced into North America from Asia, causing extensive morbidity and mortality in domestic poultry. The introduced viruses have reassorted with North American avian influenza viruses, generating viral genotypes not seen on other continents. The experiments and analyses presented here were designed to assess the impact of this genetic diversification on viral phenotypes, particularly as regards mammalian hosts, by comparing the North American viruses with their Eurasian precursor viruses.</abstract><cop>United States</cop><pub>American Society for Microbiology</pub><pmid>27303732</pmid><doi>10.1128/mSphere.00003-16</doi><oa>free_for_read</oa></addata></record> |
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subjects | avian influenza virus H5N2 H5N8 Hemagglutinins Influenza A mammals Migratory birds viral replication |
title | Novel Highly Pathogenic Avian A(H5N2) and A(H5N8) Influenza Viruses of Clade 2.3.4.4 from North America Have Limited Capacity for Replication and Transmission in Mammals |
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