The PB2 mutation with lysine at 627 enhances the pathogenicity of avian influenza (H7N9) virus which belongs to a non-zoonotic lineage

Abstract A novel avian-origin influenza A (H7N9) virus emerged in China in 2013 and has caused zoonotic disease in over 1123 persons with an overall mortality around 30%. Amino acid changes at the residues 591, 627 and 701 of polymerase basic protein 2 (PB2) have been found frequently in the human H...

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Autores principales:	Weixuan Li, Horace Hok Yeung Lee, Run Feng Li, Huachen Maria Zhu, Guan Yi, Joseph Sriyal Malik Peiris, Zi Feng Yang, Chris Ka Pun Mok
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e9b5ef361fee4efdbb2524522a1eafef
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spelling	oai:doaj.org-article:e9b5ef361fee4efdbb2524522a1eafef2021-12-02T16:06:54ZThe PB2 mutation with lysine at 627 enhances the pathogenicity of avian influenza (H7N9) virus which belongs to a non-zoonotic lineage10.1038/s41598-017-02598-z2045-2322https://doaj.org/article/e9b5ef361fee4efdbb2524522a1eafef2017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-02598-zhttps://doaj.org/toc/2045-2322Abstract A novel avian-origin influenza A (H7N9) virus emerged in China in 2013 and has caused zoonotic disease in over 1123 persons with an overall mortality around 30%. Amino acid changes at the residues 591, 627 and 701 of polymerase basic protein 2 (PB2) have been found frequently in the human H7N9 isolates but not in viruses isolated from avian species. We have recently identified a cluster of H7N9 viruses in ducks which circulated in China prior to the first recognition of zoonotic disease in 2013. These duck viruses have genetic background distinct from the zoonotic H7N9 lineage. We found that the introduction of PB2 mutation with K at 627 but not K at 591 or N at 701 to the duck H7N9 virus led to increased pathogenicity in mice. We also found that the induction of pro-inflammatory cytokines including TNF-α, IP-10, MCP-1 and MIP-1α were associated with increased severity of infection. We conclude that introduction of the mammalian adaptation mutations into the PB2 gene of duck H7N9 viruses, which are genetically unrelated to the zoonotic H7N9 lineage, can also enhance pathogenicity in mice.Weixuan LiHorace Hok Yeung LeeRun Feng LiHuachen Maria ZhuGuan YiJoseph Sriyal Malik PeirisZi Feng YangChris Ka Pun MokNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Weixuan Li Horace Hok Yeung Lee Run Feng Li Huachen Maria Zhu Guan Yi Joseph Sriyal Malik Peiris Zi Feng Yang Chris Ka Pun Mok The PB2 mutation with lysine at 627 enhances the pathogenicity of avian influenza (H7N9) virus which belongs to a non-zoonotic lineage
description	Abstract A novel avian-origin influenza A (H7N9) virus emerged in China in 2013 and has caused zoonotic disease in over 1123 persons with an overall mortality around 30%. Amino acid changes at the residues 591, 627 and 701 of polymerase basic protein 2 (PB2) have been found frequently in the human H7N9 isolates but not in viruses isolated from avian species. We have recently identified a cluster of H7N9 viruses in ducks which circulated in China prior to the first recognition of zoonotic disease in 2013. These duck viruses have genetic background distinct from the zoonotic H7N9 lineage. We found that the introduction of PB2 mutation with K at 627 but not K at 591 or N at 701 to the duck H7N9 virus led to increased pathogenicity in mice. We also found that the induction of pro-inflammatory cytokines including TNF-α, IP-10, MCP-1 and MIP-1α were associated with increased severity of infection. We conclude that introduction of the mammalian adaptation mutations into the PB2 gene of duck H7N9 viruses, which are genetically unrelated to the zoonotic H7N9 lineage, can also enhance pathogenicity in mice.
format	article
author	Weixuan Li Horace Hok Yeung Lee Run Feng Li Huachen Maria Zhu Guan Yi Joseph Sriyal Malik Peiris Zi Feng Yang Chris Ka Pun Mok
author_facet	Weixuan Li Horace Hok Yeung Lee Run Feng Li Huachen Maria Zhu Guan Yi Joseph Sriyal Malik Peiris Zi Feng Yang Chris Ka Pun Mok
author_sort	Weixuan Li
title	The PB2 mutation with lysine at 627 enhances the pathogenicity of avian influenza (H7N9) virus which belongs to a non-zoonotic lineage
title_short	The PB2 mutation with lysine at 627 enhances the pathogenicity of avian influenza (H7N9) virus which belongs to a non-zoonotic lineage
title_full	The PB2 mutation with lysine at 627 enhances the pathogenicity of avian influenza (H7N9) virus which belongs to a non-zoonotic lineage
title_fullStr	The PB2 mutation with lysine at 627 enhances the pathogenicity of avian influenza (H7N9) virus which belongs to a non-zoonotic lineage
title_full_unstemmed	The PB2 mutation with lysine at 627 enhances the pathogenicity of avian influenza (H7N9) virus which belongs to a non-zoonotic lineage
title_sort	pb2 mutation with lysine at 627 enhances the pathogenicity of avian influenza (h7n9) virus which belongs to a non-zoonotic lineage
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/e9b5ef361fee4efdbb2524522a1eafef
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The PB2 mutation with lysine at 627 enhances the pathogenicity of avian influenza (H7N9) virus which belongs to a non-zoonotic lineage

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