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

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. Thro...

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Autores principales: Bryan S. Kaplan, Marion Russier, Trushar Jeevan, Bindumadhav Marathe, Elena A. Govorkova, Charles J. Russell, Mia Kim-Torchetti, Young Ki Choi, Ian Brown, Takehiko Saito, David E. Stallknecht, Scott Krauss, Richard J. Webby
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Publicado: American Society for Microbiology 2016
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spelling oai:doaj.org-article:3e8a9bf429124b878d0b76ff4e6c4d882021-11-15T15:21:23ZNovel 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 Mammals10.1128/mSphere.00003-162379-5042https://doaj.org/article/3e8a9bf429124b878d0b76ff4e6c4d882016-04-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00003-16https://doaj.org/toc/2379-5042ABSTRACT 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.Bryan S. KaplanMarion RussierTrushar JeevanBindumadhav MaratheElena A. GovorkovaCharles J. RussellMia Kim-TorchettiYoung Ki ChoiIan BrownTakehiko SaitoDavid E. StallknechtScott KraussRichard J. WebbyAmerican Society for Microbiologyarticleavian influenza virusH5N2H5N8mammalsviral replicationMicrobiologyQR1-502ENmSphere, Vol 1, Iss 2 (2016)
institution DOAJ
collection DOAJ
language EN
topic avian influenza virus
H5N2
H5N8
mammals
viral replication
Microbiology
QR1-502
spellingShingle avian influenza virus
H5N2
H5N8
mammals
viral replication
Microbiology
QR1-502
Bryan S. Kaplan
Marion Russier
Trushar Jeevan
Bindumadhav Marathe
Elena A. Govorkova
Charles J. Russell
Mia Kim-Torchetti
Young Ki Choi
Ian Brown
Takehiko Saito
David E. Stallknecht
Scott Krauss
Richard J. Webby
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
description 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.
format article
author Bryan S. Kaplan
Marion Russier
Trushar Jeevan
Bindumadhav Marathe
Elena A. Govorkova
Charles J. Russell
Mia Kim-Torchetti
Young Ki Choi
Ian Brown
Takehiko Saito
David E. Stallknecht
Scott Krauss
Richard J. Webby
author_facet Bryan S. Kaplan
Marion Russier
Trushar Jeevan
Bindumadhav Marathe
Elena A. Govorkova
Charles J. Russell
Mia Kim-Torchetti
Young Ki Choi
Ian Brown
Takehiko Saito
David E. Stallknecht
Scott Krauss
Richard J. Webby
author_sort Bryan S. Kaplan
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_short 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_full 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_fullStr 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_full_unstemmed 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_sort 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
publisher American Society for Microbiology
publishDate 2016
url https://doaj.org/article/3e8a9bf429124b878d0b76ff4e6c4d88
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