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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| Format: | Article |
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Nature Portfolio
2017-05-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-017-02598-z |
| _version_ | 1818994905323667456 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-20T21:05:22Z |
| format | Article |
| id | doaj.art-e9b5ef361fee4efdbb2524522a1eafef |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-20T21:05:22Z |
| publishDate | 2017-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-e9b5ef361fee4efdbb2524522a1eafef2022-12-21T19:26:36ZengNature PortfolioScientific Reports2045-23222017-05-017111110.1038/s41598-017-02598-zThe PB2 mutation with lysine at 627 enhances the pathogenicity of avian influenza (H7N9) virus which belongs to a non-zoonotic lineageWeixuan Li0Horace Hok Yeung Lee1Run Feng Li2Huachen Maria Zhu3Guan Yi4Joseph Sriyal Malik Peiris5Zi Feng Yang6Chris Ka Pun Mok7Department of clinical laboratory, First people’s hospital of FoshanHKU-Pasteur Research Pole, School of Public Health, HKU Li Ka Shing Faculty of Medicine, The University of Hong KongState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, First Affiliated Hospital of Guangzhou Medical UniversityCentre of Influenza Research, School of Public Health, HKU Li Ka Shing Faculty of Medicine, The University of Hong KongCentre of Influenza Research, School of Public Health, HKU Li Ka Shing Faculty of Medicine, The University of Hong KongHKU-Pasteur Research Pole, School of Public Health, HKU Li Ka Shing Faculty of Medicine, The University of Hong KongState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, First Affiliated Hospital of Guangzhou Medical UniversityHKU-Pasteur Research Pole, School of Public Health, HKU Li Ka Shing Faculty of Medicine, The University of Hong KongAbstract 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.https://doi.org/10.1038/s41598-017-02598-z |
| spellingShingle | 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 Scientific Reports |
| title | 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_short | 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 |
| url | https://doi.org/10.1038/s41598-017-02598-z |
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