Atomic Resolution Structure of the Oncolytic Parvovirus LuIII by Electron Microscopy and 3D Image Reconstruction
AbstractLuIII, 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
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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.
Pittman N, Misseldine A, Geilen L, Halder S, Smith JK, Kurian J, Chipman P, Janssen M, Mckenna R, Baker TS, 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(11):321.Chicago/Turabian Style
Pittman, Nikéa; Misseldine, Adam; Geilen, Lorena; Halder, Sujata; Smith, J. K.; Kurian, Justin; Chipman, Paul; Janssen, Mandy; Mckenna, Robert; Baker, Timothy S.; D’Abramo Jr., Anthony; Cotmore, Susan; Tattersall, Peter; Agbandje-McKenna, Mavis. 2017. "Atomic Resolution Structure of the Oncolytic Parvovirus LuIII by Electron Microscopy and 3D Image Reconstruction." Viruses 9, no. 11: 321.
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