Format

Send to

Choose Destination
Viruses. 2017 Oct 30;9(11). pii: E321. doi: 10.3390/v9110321.

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

Author information

1
Department of Biochemistry and Molecular Biology, University of Florida, Gainesville, FL 32611, USA. nikea@ufl.edu.
2
Center for Structural Biology, The McKnight Brain Institute, University of Florida, Gainesville, FL 32611, USA. nikea@ufl.edu.
3
Department of Biochemistry and Molecular Biology, University of Florida, Gainesville, FL 32611, USA. adammisseldine@ufl.edu.
4
Center for Structural Biology, The McKnight Brain Institute, University of Florida, Gainesville, FL 32611, USA. adammisseldine@ufl.edu.
5
Department of Biochemistry and Molecular Biology, University of Florida, Gainesville, FL 32611, USA. lorenageilen@ufl.edu.
6
Center for Structural Biology, The McKnight Brain Institute, University of Florida, Gainesville, FL 32611, USA. lorenageilen@ufl.edu.
7
Department of Biochemistry and Molecular Biology, University of Florida, Gainesville, FL 32611, USA. halder.sujata@gmail.com.
8
Center for Structural Biology, The McKnight Brain Institute, University of Florida, Gainesville, FL 32611, USA. halder.sujata@gmail.com.
9
Department of Biochemistry and Molecular Biology, University of Florida, Gainesville, FL 32611, USA. jkennonsmith@ufl.edu.
10
Center for Structural Biology, The McKnight Brain Institute, University of Florida, Gainesville, FL 32611, USA. jkennonsmith@ufl.edu.
11
Department of Biochemistry and Molecular Biology, University of Florida, Gainesville, FL 32611, USA. justinkurian@ufl.edu.
12
Center for Structural Biology, The McKnight Brain Institute, University of Florida, Gainesville, FL 32611, USA. justinkurian@ufl.edu.
13
Department of Biochemistry and Molecular Biology, University of Florida, Gainesville, FL 32611, USA. pchipman@ufl.edu.
14
Center for Structural Biology, The McKnight Brain Institute, University of Florida, Gainesville, FL 32611, USA. pchipman@ufl.edu.
15
Department of Chemistry and Biochemistry and Division of Biological Sciences, University of California-San Diego, San Diego, CA 92093, USA. mjanssen@nanoimagingservices.com.
16
Department of Biochemistry and Molecular Biology, University of Florida, Gainesville, FL 32611, USA. rmckenna@ufl.edu.
17
Center for Structural Biology, The McKnight Brain Institute, University of Florida, Gainesville, FL 32611, USA. rmckenna@ufl.edu.
18
Department of Chemistry and Biochemistry and Division of Biological Sciences, University of California-San Diego, San Diego, CA 92093, USA. tsb@ucsd.edu.
19
Department of Laboratory Medicine, Yale University Medical School, New Haven, CT 06520, USA. anthony.dabramo@yale.edu.
20
Department of Laboratory Medicine, Yale University Medical School, New Haven, CT 06520, USA. susan.cotmore@yale.edu.
21
Department of Laboratory Medicine, Yale University Medical School, New Haven, CT 06520, USA. peter.tattersall@yale.edu.
22
Department of Genetics, Yale University Medical School, New Haven, CT 06510, USA. peter.tattersall@yale.edu.
23
Department of Biochemistry and Molecular Biology, University of Florida, Gainesville, FL 32611, USA. mckenna@ufl.edu.
24
Center for Structural Biology, The McKnight Brain Institute, University of Florida, Gainesville, FL 32611, USA. mckenna@ufl.edu.

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.

KEYWORDS:

Parvoviridae; cryo-electron microscopy; oncolytic virotherapy; structural virology

PMID:
29084163
PMCID:
PMC5707528
DOI:
10.3390/v9110321
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Multidisciplinary Digital Publishing Institute (MDPI) Icon for PubMed Central
Loading ...
Support Center