Cryo EM Analysis Reveals Inherent Flexibility of Authentic Murine Papillomavirus Capsids
Human papillomavirus (HPV) is a significant health burden and leading cause of virus-induced cancers. However, studies have been hampered due to restricted tropism that makes production and purification of high titer virus problematic. This issue has been overcome by developing alternative HPV produ...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-10-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/13/10/2023 |
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| author | Samantha R. Hartmann Daniel J. Goetschius Jiafen Hu Joshua J. Graff Carol M. Bator Neil D. Christensen Susan L. Hafenstein |
| author_facet | Samantha R. Hartmann Daniel J. Goetschius Jiafen Hu Joshua J. Graff Carol M. Bator Neil D. Christensen Susan L. Hafenstein |
| author_sort | Samantha R. Hartmann |
| collection | DOAJ |
| description | Human papillomavirus (HPV) is a significant health burden and leading cause of virus-induced cancers. However, studies have been hampered due to restricted tropism that makes production and purification of high titer virus problematic. This issue has been overcome by developing alternative HPV production methods such as virus-like particles (VLPs), which are devoid of a native viral genome. Structural studies have been limited in resolution due to the heterogeneity, fragility, and stability of the VLP capsids. The mouse papillomavirus (MmuPV1) presented here has provided the opportunity to study a native papillomavirus in the context of a common laboratory animal. Using cryo EM to solve the structure of MmuPV1, we achieved 3.3 Å resolution with a local symmetry refinement method that defined smaller, symmetry related subparticles. The resulting high-resolution structure allowed us to build the MmuPV1 asymmetric unit for the first time and identify putative L2 density. We also used our program ISECC to quantify capsid flexibility, which revealed that capsomers move as rigid bodies connected by flexible linkers. The MmuPV1 flexibility was comparable to that of a HPV VLP previously characterized. The resulting MmuPV1 structure is a promising step forward in the study of papillomavirus and will provide a framework for continuing biochemical, genetic, and biophysical research for papillomaviruses. |
| first_indexed | 2024-03-10T06:09:03Z |
| format | Article |
| id | doaj.art-fc77a8772a78492a91c40dfcca533a5e |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-10T06:09:03Z |
| publishDate | 2021-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-fc77a8772a78492a91c40dfcca533a5e2023-11-22T20:19:35ZengMDPI AGViruses1999-49152021-10-011310202310.3390/v13102023Cryo EM Analysis Reveals Inherent Flexibility of Authentic Murine Papillomavirus CapsidsSamantha R. Hartmann0Daniel J. Goetschius1Jiafen Hu2Joshua J. Graff3Carol M. Bator4Neil D. Christensen5Susan L. Hafenstein6Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA 16802, USADepartment of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA 16802, USADepartment of Pathology, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USADepartment of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA 16802, USAHuck Institutes of the Life Sciences, The Pennsylvania State University, University Park, PA 16802, USADepartment of Pathology, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USADepartment of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA 16802, USAHuman papillomavirus (HPV) is a significant health burden and leading cause of virus-induced cancers. However, studies have been hampered due to restricted tropism that makes production and purification of high titer virus problematic. This issue has been overcome by developing alternative HPV production methods such as virus-like particles (VLPs), which are devoid of a native viral genome. Structural studies have been limited in resolution due to the heterogeneity, fragility, and stability of the VLP capsids. The mouse papillomavirus (MmuPV1) presented here has provided the opportunity to study a native papillomavirus in the context of a common laboratory animal. Using cryo EM to solve the structure of MmuPV1, we achieved 3.3 Å resolution with a local symmetry refinement method that defined smaller, symmetry related subparticles. The resulting high-resolution structure allowed us to build the MmuPV1 asymmetric unit for the first time and identify putative L2 density. We also used our program ISECC to quantify capsid flexibility, which revealed that capsomers move as rigid bodies connected by flexible linkers. The MmuPV1 flexibility was comparable to that of a HPV VLP previously characterized. The resulting MmuPV1 structure is a promising step forward in the study of papillomavirus and will provide a framework for continuing biochemical, genetic, and biophysical research for papillomaviruses.https://www.mdpi.com/1999-4915/13/10/2023mouse papillomaviruscryo EMHPV16 |
| spellingShingle | Samantha R. Hartmann Daniel J. Goetschius Jiafen Hu Joshua J. Graff Carol M. Bator Neil D. Christensen Susan L. Hafenstein Cryo EM Analysis Reveals Inherent Flexibility of Authentic Murine Papillomavirus Capsids Viruses mouse papillomavirus cryo EM HPV16 |
| title | Cryo EM Analysis Reveals Inherent Flexibility of Authentic Murine Papillomavirus Capsids |
| title_full | Cryo EM Analysis Reveals Inherent Flexibility of Authentic Murine Papillomavirus Capsids |
| title_fullStr | Cryo EM Analysis Reveals Inherent Flexibility of Authentic Murine Papillomavirus Capsids |
| title_full_unstemmed | Cryo EM Analysis Reveals Inherent Flexibility of Authentic Murine Papillomavirus Capsids |
| title_short | Cryo EM Analysis Reveals Inherent Flexibility of Authentic Murine Papillomavirus Capsids |
| title_sort | cryo em analysis reveals inherent flexibility of authentic murine papillomavirus capsids |
| topic | mouse papillomavirus cryo EM HPV16 |
| url | https://www.mdpi.com/1999-4915/13/10/2023 |
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