Probing the functional constraints of influenza A virus NEP by deep mutational scanning
Summary: The influenza A virus nuclear export protein (NEP) is a multifunctional protein that is essential for the viral life cycle and has very high sequence conservation. However, since the open reading frame of NEP largely overlaps with that of another influenza viral protein, non-structural prot...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-01-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S221112472401547X |
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| author | Qi Wen Teo Yiquan Wang Huibin Lv Michael S. Oade Kevin J. Mao Timothy J.C. Tan Yang Wei Huan Joel Rivera-Cardona Evan K. Shao Danbi Choi Chaoyang Wang Zahra Tavakoli Dargani Christopher B. Brooke Aartjan J.W. te Velthuis Nicholas C. Wu |
| author_facet | Qi Wen Teo Yiquan Wang Huibin Lv Michael S. Oade Kevin J. Mao Timothy J.C. Tan Yang Wei Huan Joel Rivera-Cardona Evan K. Shao Danbi Choi Chaoyang Wang Zahra Tavakoli Dargani Christopher B. Brooke Aartjan J.W. te Velthuis Nicholas C. Wu |
| author_sort | Qi Wen Teo |
| collection | DOAJ |
| description | Summary: The influenza A virus nuclear export protein (NEP) is a multifunctional protein that is essential for the viral life cycle and has very high sequence conservation. However, since the open reading frame of NEP largely overlaps with that of another influenza viral protein, non-structural protein 1, it is difficult to infer the functional constraints of NEP based on sequence conservation analysis. In addition, the N-terminal of NEP is structurally disordered, which further complicates the understanding of its function. Here, we systematically measure the replication fitness effects of >1,800 mutations of NEP. Our results show that the N-terminal domain has high mutational tolerance. Additional experiments show that N-terminal domain mutations affect viral transcription and replication dynamics, host cellular responses, and mammalian adaptation of avian influenza virus. Overall, our study not only advances the functional understanding of NEP but also provides insights into its evolutionary constraints. |
| format | Article |
| id | doaj-art-f745484899b9413489ca4d40589a9b80 |
| institution | Kabale University |
| issn | 2211-1247 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj-art-f745484899b9413489ca4d40589a9b802025-01-16T04:28:34ZengElsevierCell Reports2211-12472025-01-01441115196Probing the functional constraints of influenza A virus NEP by deep mutational scanningQi Wen Teo0Yiquan Wang1Huibin Lv2Michael S. Oade3Kevin J. Mao4Timothy J.C. Tan5Yang Wei Huan6Joel Rivera-Cardona7Evan K. Shao8Danbi Choi9Chaoyang Wang10Zahra Tavakoli Dargani11Christopher B. Brooke12Aartjan J.W. te Velthuis13Nicholas C. Wu14Department of Biochemistry, University of Illinois Urbana-Champaign, Urbana, IL 61801, USA; Carl R. Woese Institute for Genomic Biology, University of Illinois Urbana-Champaign, Urbana, IL 61801, USADepartment of Biochemistry, University of Illinois Urbana-Champaign, Urbana, IL 61801, USADepartment of Biochemistry, University of Illinois Urbana-Champaign, Urbana, IL 61801, USA; Carl R. Woese Institute for Genomic Biology, University of Illinois Urbana-Champaign, Urbana, IL 61801, USADepartment of Molecular Biology, Princeton University, Washington Road, Princeton, NJ 08544, USADepartment of Biochemistry, University of Illinois Urbana-Champaign, Urbana, IL 61801, USACenter for Biophysics and Quantitative Biology, University of Illinois Urbana-Champaign, Urbana, IL 61801, USADepartment of Biochemistry, University of Illinois Urbana-Champaign, Urbana, IL 61801, USADepartment of Microbiology, University of Illinois Urbana-Champaign, Urbana, IL 61801, USADepartment of Biochemistry, University of Illinois Urbana-Champaign, Urbana, IL 61801, USADepartment of Biochemistry, University of Illinois Urbana-Champaign, Urbana, IL 61801, USADepartment of Biochemistry, University of Illinois Urbana-Champaign, Urbana, IL 61801, USADepartment of Biochemistry, University of Illinois Urbana-Champaign, Urbana, IL 61801, USACarl R. Woese Institute for Genomic Biology, University of Illinois Urbana-Champaign, Urbana, IL 61801, USA; Department of Microbiology, University of Illinois Urbana-Champaign, Urbana, IL 61801, USADepartment of Molecular Biology, Princeton University, Washington Road, Princeton, NJ 08544, USADepartment of Biochemistry, University of Illinois Urbana-Champaign, Urbana, IL 61801, USA; Carl R. Woese Institute for Genomic Biology, University of Illinois Urbana-Champaign, Urbana, IL 61801, USA; Center for Biophysics and Quantitative Biology, University of Illinois Urbana-Champaign, Urbana, IL 61801, USA; Carle Illinois College of Medicine, University of Illinois Urbana-Champaign, Urbana, IL 61801, USA; Corresponding authorSummary: The influenza A virus nuclear export protein (NEP) is a multifunctional protein that is essential for the viral life cycle and has very high sequence conservation. However, since the open reading frame of NEP largely overlaps with that of another influenza viral protein, non-structural protein 1, it is difficult to infer the functional constraints of NEP based on sequence conservation analysis. In addition, the N-terminal of NEP is structurally disordered, which further complicates the understanding of its function. Here, we systematically measure the replication fitness effects of >1,800 mutations of NEP. Our results show that the N-terminal domain has high mutational tolerance. Additional experiments show that N-terminal domain mutations affect viral transcription and replication dynamics, host cellular responses, and mammalian adaptation of avian influenza virus. Overall, our study not only advances the functional understanding of NEP but also provides insights into its evolutionary constraints.http://www.sciencedirect.com/science/article/pii/S221112472401547XCP: MicrobiologyCP: Molecular biology |
| spellingShingle | Qi Wen Teo Yiquan Wang Huibin Lv Michael S. Oade Kevin J. Mao Timothy J.C. Tan Yang Wei Huan Joel Rivera-Cardona Evan K. Shao Danbi Choi Chaoyang Wang Zahra Tavakoli Dargani Christopher B. Brooke Aartjan J.W. te Velthuis Nicholas C. Wu Probing the functional constraints of influenza A virus NEP by deep mutational scanning Cell Reports CP: Microbiology CP: Molecular biology |
| title | Probing the functional constraints of influenza A virus NEP by deep mutational scanning |
| title_full | Probing the functional constraints of influenza A virus NEP by deep mutational scanning |
| title_fullStr | Probing the functional constraints of influenza A virus NEP by deep mutational scanning |
| title_full_unstemmed | Probing the functional constraints of influenza A virus NEP by deep mutational scanning |
| title_short | Probing the functional constraints of influenza A virus NEP by deep mutational scanning |
| title_sort | probing the functional constraints of influenza a virus nep by deep mutational scanning |
| topic | CP: Microbiology CP: Molecular biology |
| url | http://www.sciencedirect.com/science/article/pii/S221112472401547X |
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