Key Role of the Influenza A Virus PA Gene Segment in the Emergence of Pandemic Viruses
Influenza A viruses (IAVs) are a significant human pathogen that cause seasonal epidemics and occasional pandemics. Avian waterfowl are the natural reservoir of IAVs, but a wide range of species can serve as hosts. Most IAV strains are adapted to one host species and avian strains of IAV replicate p...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-03-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/12/4/365 |
| _version_ | 1818019473799512064 |
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| author | Michael M. Lutz IV Megan M. Dunagan Yuki Kurebayashi Toru Takimoto |
| author_facet | Michael M. Lutz IV Megan M. Dunagan Yuki Kurebayashi Toru Takimoto |
| author_sort | Michael M. Lutz IV |
| collection | DOAJ |
| description | Influenza A viruses (IAVs) are a significant human pathogen that cause seasonal epidemics and occasional pandemics. Avian waterfowl are the natural reservoir of IAVs, but a wide range of species can serve as hosts. Most IAV strains are adapted to one host species and avian strains of IAV replicate poorly in most mammalian hosts. Importantly, IAV polymerases from avian strains function poorly in mammalian cells but host adaptive mutations can restore activity. The 2009 pandemic H1N1 (H1N1pdm09) virus acquired multiple mutations in the PA gene that activated polymerase activity in mammalian cells, even in the absence of previously identified host adaptive mutations in other polymerase genes. These mutations in PA localize within different regions of the protein suggesting multiple mechanisms exist to activate polymerase activity. Additionally, an immunomodulatory protein, PA-X, is expressed from the PA gene segment. PA-X expression is conserved amongst many IAV strains but activity varies between viruses specific for different hosts, suggesting that PA-X also plays a role in host adaptation. Here, we review the role of PA in the emergence of currently circulating H1N1pdm09 viruses and the most recent studies of host adaptive mutations in the PA gene that modulate polymerase activity and PA-X function. |
| first_indexed | 2024-04-14T07:52:58Z |
| format | Article |
| id | doaj.art-81a8cbbfc87248d28d3d75388b2e7459 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-04-14T07:52:58Z |
| publishDate | 2020-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-81a8cbbfc87248d28d3d75388b2e74592022-12-22T02:05:08ZengMDPI AGViruses1999-49152020-03-0112436510.3390/v12040365v12040365Key Role of the Influenza A Virus PA Gene Segment in the Emergence of Pandemic VirusesMichael M. Lutz IV0Megan M. Dunagan1Yuki Kurebayashi2Toru Takimoto3Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY 14642 USADepartment of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY 14642 USADepartment of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY 14642 USADepartment of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY 14642 USAInfluenza A viruses (IAVs) are a significant human pathogen that cause seasonal epidemics and occasional pandemics. Avian waterfowl are the natural reservoir of IAVs, but a wide range of species can serve as hosts. Most IAV strains are adapted to one host species and avian strains of IAV replicate poorly in most mammalian hosts. Importantly, IAV polymerases from avian strains function poorly in mammalian cells but host adaptive mutations can restore activity. The 2009 pandemic H1N1 (H1N1pdm09) virus acquired multiple mutations in the PA gene that activated polymerase activity in mammalian cells, even in the absence of previously identified host adaptive mutations in other polymerase genes. These mutations in PA localize within different regions of the protein suggesting multiple mechanisms exist to activate polymerase activity. Additionally, an immunomodulatory protein, PA-X, is expressed from the PA gene segment. PA-X expression is conserved amongst many IAV strains but activity varies between viruses specific for different hosts, suggesting that PA-X also plays a role in host adaptation. Here, we review the role of PA in the emergence of currently circulating H1N1pdm09 viruses and the most recent studies of host adaptive mutations in the PA gene that modulate polymerase activity and PA-X function.https://www.mdpi.com/1999-4915/12/4/365host adaptationinfluenza a viruspapa-xrna-dependent rna polymerase |
| spellingShingle | Michael M. Lutz IV Megan M. Dunagan Yuki Kurebayashi Toru Takimoto Key Role of the Influenza A Virus PA Gene Segment in the Emergence of Pandemic Viruses Viruses host adaptation influenza a virus pa pa-x rna-dependent rna polymerase |
| title | Key Role of the Influenza A Virus PA Gene Segment in the Emergence of Pandemic Viruses |
| title_full | Key Role of the Influenza A Virus PA Gene Segment in the Emergence of Pandemic Viruses |
| title_fullStr | Key Role of the Influenza A Virus PA Gene Segment in the Emergence of Pandemic Viruses |
| title_full_unstemmed | Key Role of the Influenza A Virus PA Gene Segment in the Emergence of Pandemic Viruses |
| title_short | Key Role of the Influenza A Virus PA Gene Segment in the Emergence of Pandemic Viruses |
| title_sort | key role of the influenza a virus pa gene segment in the emergence of pandemic viruses |
| topic | host adaptation influenza a virus pa pa-x rna-dependent rna polymerase |
| url | https://www.mdpi.com/1999-4915/12/4/365 |
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