Cryo EM Analysis Reveals Inherent Flexibility of Authentic Murine Papillomavirus Capsids.

Publisher: MDPI Country of Publication: Switzerland NLM ID: 101509722 Publication Model: Electronic Cited Medium: Internet ISSN: 1999-4915 (Electronic) Linking ISSN: 19994915 NLM ISO Abbreviation: Viruses Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI

Cryoelectron Microscopy*; Capsid/*chemistry ; Capsid/*ultrastructure ; Papillomaviridae/*ultrastructure; Animals ; Capsid Proteins ; Genome, Viral ; Mice ; Models, Molecular ; Oncogene Proteins, Viral ; Papillomaviridae/genetics ; Papillomavirus Infections/virology ; Viruses, Unclassified/classification ; Viruses, Unclassified/genetics

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.

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R01 AI134910 United States AI NIAID NIH HHS; S10 OD026822 United States OD NIH HHS; S10 OD026822-01 NIH Office of the Director; Al134910-01A1 NIH Office of the Director

Keywords: HPV16; cryo EM; mouse papillomavirus

0 (Capsid Proteins)
0 (Oncogene Proteins, Viral)

Date Created: 20211026 Date Completed: 20220207 Latest Revision: 20220716

20221213

PMC8537154

10.3390/v13102023

34696452