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. 2020 Mar 9;10:4307. doi: 10.1038/s41598-020-61275-w

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© The Author(s) 2020

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Schematic representation of the genome of the replication conditional, ERBB2-retargeted SurE_oHSV virus. (a) The region of the gD glycoprotein (6–38 aa) in the Survivin_oHSV backbone was substituted by a ERBB2 scFv sequence for general detargeting from cellular receptors mediating viral entry and retargeting to ERBB2⁺ cells. The new oncolytic virus was named SurE_oHSV (SurvivinErbb2_oncolyticHSV). (b) Replicative potential and spread (c) of double regulated SurE_oHSV were evaluated in comparison to single regulated viruses (Survivin_oHSV and R-LM113) and wild type R-LM55 virus in tumour SKOV3 and normal MRC5 cells infected with 0.03 PFU/cell. Viral genome copies were titrated 48 h post infection. Statistical significance was calculated comparing SurE_oHSV to all the other viruses (d). Cytotoxicity induced by wild type, single and double regulated viruses in normal MRC5 and tumour SKOV3 cells was evaluated according to Lactic Acid Dehydrogenase (LDH) release in cell supernatant in time course of infection from 24 to 96 hours post infection with 0.1 PFU/cell. The asterisks in the Panels b and d indicate the P values: *P < 0.05; **P < 0.005; ***P < 0.0005.