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

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 map...

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Autores principales: Pittman, Nikéa, Misseldine, Adam, Geilen, Lorena, Halder, Sujata, Smith, J. Kennon, Kurian, Justin, Chipman, Paul, Janssen, Mandy, Mckenna, Robert, Baker, Timothy S., D’Abramo, Anthony, Cotmore, Susan, Tattersall, Peter, Agbandje-McKenna, Mavis
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5707528/
https://www.ncbi.nlm.nih.gov/pubmed/29084163
http://dx.doi.org/10.3390/v9110321
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author Pittman, Nikéa
Misseldine, Adam
Geilen, Lorena
Halder, Sujata
Smith, J. Kennon
Kurian, Justin
Chipman, Paul
Janssen, Mandy
Mckenna, Robert
Baker, Timothy S.
D’Abramo, Anthony
Cotmore, Susan
Tattersall, Peter
Agbandje-McKenna, Mavis
author_facet Pittman, Nikéa
Misseldine, Adam
Geilen, Lorena
Halder, Sujata
Smith, J. Kennon
Kurian, Justin
Chipman, Paul
Janssen, Mandy
Mckenna, Robert
Baker, Timothy S.
D’Abramo, Anthony
Cotmore, Susan
Tattersall, Peter
Agbandje-McKenna, Mavis
author_sort Pittman, Nikéa
collection PubMed
description 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.
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spelling pubmed-57075282017-12-05 Atomic Resolution Structure of the Oncolytic Parvovirus LuIII by Electron Microscopy and 3D Image Reconstruction Pittman, Nikéa Misseldine, Adam Geilen, Lorena Halder, Sujata Smith, J. Kennon Kurian, Justin Chipman, Paul Janssen, Mandy Mckenna, Robert Baker, Timothy S. D’Abramo, Anthony Cotmore, Susan Tattersall, Peter Agbandje-McKenna, Mavis Viruses Article 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. MDPI 2017-10-30 /pmc/articles/PMC5707528/ /pubmed/29084163 http://dx.doi.org/10.3390/v9110321 Text en © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Pittman, Nikéa
Misseldine, Adam
Geilen, Lorena
Halder, Sujata
Smith, J. Kennon
Kurian, Justin
Chipman, Paul
Janssen, Mandy
Mckenna, Robert
Baker, Timothy S.
D’Abramo, Anthony
Cotmore, Susan
Tattersall, Peter
Agbandje-McKenna, Mavis
Atomic Resolution Structure of the Oncolytic Parvovirus LuIII by Electron Microscopy and 3D Image Reconstruction
title Atomic Resolution Structure of the Oncolytic Parvovirus LuIII by Electron Microscopy and 3D Image Reconstruction
title_full Atomic Resolution Structure of the Oncolytic Parvovirus LuIII by Electron Microscopy and 3D Image Reconstruction
title_fullStr Atomic Resolution Structure of the Oncolytic Parvovirus LuIII by Electron Microscopy and 3D Image Reconstruction
title_full_unstemmed Atomic Resolution Structure of the Oncolytic Parvovirus LuIII by Electron Microscopy and 3D Image Reconstruction
title_short Atomic Resolution Structure of the Oncolytic Parvovirus LuIII by Electron Microscopy and 3D Image Reconstruction
title_sort atomic resolution structure of the oncolytic parvovirus luiii by electron microscopy and 3d image reconstruction
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5707528/
https://www.ncbi.nlm.nih.gov/pubmed/29084163
http://dx.doi.org/10.3390/v9110321
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