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Open AccessArticle

Mutations in the Non-Structural Protein-Coding Sequence of Protoparvovirus H-1PV Enhance the Fitness of the Virus and Show Key Benefits Regarding the Transduction Efficiency of Derived Vectors

1
Infection, Inflammation and Cancer Program, Tumor Virology Division (F010), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 242, 69120 Heidelberg, Germany
2
Institut National de la Santé et de la Recherche Médicale U701, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
3
INSERM U1109, UDS Institut de Virologie, 3 rue Koeberle, 67091 Strasbourg CEDEX, France
*
Authors to whom correspondence should be addressed.
Viruses 2018, 10(4), 150; https://doi.org/10.3390/v10040150
Received: 26 January 2018 / Revised: 23 March 2018 / Accepted: 26 March 2018 / Published: 27 March 2018
(This article belongs to the Special Issue Protoparvoviruses: Friends or Foes?)
Single nucleotide changes were introduced into the non-structural (NS) coding sequence of the H-1 parvovirus (PV) infectious molecular clone and the corresponding virus stocks produced, thereby generating H1-PM-I, H1-PM-II, H1-PM-III, and H1-DM. The effects of the mutations on viral fitness were analyzed. Because of the overlapping sequences of NS1 and NS2, the mutations affected either NS2 (H1-PM-II, -III) or both NS1 and NS2 proteins (H1-PM-I, H1-DM). Our results show key benefits of PM-I, PM-II, and DM mutations with regard to the fitness of the virus stocks produced. Indeed, these mutants displayed a higher production of infectious virus in different cell cultures and better spreading capacity than the wild-type virus. This correlated with a decreased particle-to-infectivity (P/I) ratio and stimulation of an early step(s) of the viral cycle prior to viral DNA replication, namely, cell binding and internalization. These mutations also enhance the transduction efficiency of H-1PV-based vectors. In contrast, the PM-III mutation, which affects NS2 at a position downstream of the sequence deleted in Del H-1PV, impaired virus replication and spreading. We hypothesize that the NS2 protein—modified in H1-PM-I, H1-PM-II, and H1-DM—may result in the stimulation of some maturation step(s) of the capsid and facilitate virus entry into subsequently infected cells. View Full-Text
Keywords: protoparvovirus H-1PV; fitness mutants; parvoviral vectors protoparvovirus H-1PV; fitness mutants; parvoviral vectors
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MDPI and ACS Style

Hashemi, H.; Condurat, A.-L.; Stroh-Dege, A.; Weiss, N.; Geiss, C.; Pilet, J.; Cornet Bartolomé, C.; Rommelaere, J.; Salomé, N.; Dinsart, C. Mutations in the Non-Structural Protein-Coding Sequence of Protoparvovirus H-1PV Enhance the Fitness of the Virus and Show Key Benefits Regarding the Transduction Efficiency of Derived Vectors. Viruses 2018, 10, 150. https://doi.org/10.3390/v10040150

AMA Style

Hashemi H, Condurat A-L, Stroh-Dege A, Weiss N, Geiss C, Pilet J, Cornet Bartolomé C, Rommelaere J, Salomé N, Dinsart C. Mutations in the Non-Structural Protein-Coding Sequence of Protoparvovirus H-1PV Enhance the Fitness of the Virus and Show Key Benefits Regarding the Transduction Efficiency of Derived Vectors. Viruses. 2018; 10(4):150. https://doi.org/10.3390/v10040150

Chicago/Turabian Style

Hashemi, Hamidreza; Condurat, Alexandra-Larisa; Stroh-Dege, Alexandra; Weiss, Nadine; Geiss, Carsten; Pilet, Jill; Cornet Bartolomé, Carles; Rommelaere, Jean; Salomé, Nathalie; Dinsart, Christiane. 2018. "Mutations in the Non-Structural Protein-Coding Sequence of Protoparvovirus H-1PV Enhance the Fitness of the Virus and Show Key Benefits Regarding the Transduction Efficiency of Derived Vectors" Viruses 10, no. 4: 150. https://doi.org/10.3390/v10040150

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