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Viruses 2017, 9(11), 321; doi:10.3390/v9110321

Atomic Resolution Structure of the Oncolytic Parvovirus LuIII by Electron Microscopy and 3D Image Reconstruction

1
Department of Biochemistry and Molecular Biology, University of Florida, Gainesville, FL 32611, USA
2
Center for Structural Biology, The McKnight Brain Institute, University of Florida, Gainesville, FL 32611, USA
3
Department of Chemistry and Biochemistry and Division of Biological Sciences, University of California-San Diego, San Diego, CA 92093, USA
4
Department of Laboratory Medicine, Yale University Medical School, New Haven, CT 06520, USA
5
Department of Genetics, Yale University Medical School, New Haven, CT 06510, USA
Current address: Zydus Research Centre, Biotech Division, Cadila Healthcare Ltd., The Zydus Group, Ahmedabad, Gujarat 380015, India.
Current address: NanoImaging Services, Inc., 4940 Carroll Canyon Road, Suite 115, San Diego, CA 92121, USA.
*
Author to whom correspondence should be addressed.
Received: 16 October 2017 / Revised: 27 October 2017 / Accepted: 27 October 2017 / Published: 30 October 2017
(This article belongs to the Special Issue Protoparvoviruses: Friends or Foes?)
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Abstract

LuIII, a protoparvovirus pathogenic to rodents, replicates in human mitotic cells, making it applicable for use to kill cancer cells. This virus group includes H-1 parvovirus (H-1PV) and minute virus of mice (MVM). However, LuIII displays enhanced oncolysis compared to H-1PV and MVM, a phenotype mapped to the major capsid viral protein 2 (VP2). This suggests that within LuIII VP2 are determinants for improved tumor lysis. To investigate this, the structure of the LuIII virus-like-particle was determined using single particle cryo-electron microscopy and image reconstruction to 3.17 Å resolution, and compared to the H-1PV and MVM structures. The LuIII VP2 structure, ordered from residue 37 to 587 (C-terminal), had the conserved VP topology and capsid morphology previously reported for other protoparvoviruses. This includes a core β-barrel and α-helix A, a depression at the icosahedral 2-fold and surrounding the 5-fold axes, and a single protrusion at the 3-fold axes. Comparative analysis identified surface loop differences among LuIII, H-1PV, and MVM at or close to the capsid 2- and 5-fold symmetry axes, and the shoulder of the 3-fold protrusions. The 2-fold differences cluster near the previously identified MVM sialic acid receptor binding pocket, and revealed potential determinants of protoparvovirus tumor tropism. View Full-Text
Keywords: cryo-electron microscopy; oncolytic virotherapy; Parvoviridae; structural virology cryo-electron microscopy; oncolytic virotherapy; Parvoviridae; structural virology
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MDPI and ACS Style

Pittman, N.; Misseldine, A.; Geilen, L.; Halder, S.; Smith, J.K.; Kurian, J.; Chipman, P.; Janssen, M.; Mckenna, R.; Baker, T.S.; D’Abramo Jr., A.; Cotmore, S.; Tattersall, P.; Agbandje-McKenna, M. Atomic Resolution Structure of the Oncolytic Parvovirus LuIII by Electron Microscopy and 3D Image Reconstruction. Viruses 2017, 9, 321.

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