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The In Vitro Replication, Spread, and Oncolytic Potential of Finnish Circulating Strains of Herpes Simplex Virus Type 1

Herpes simplex virus type 1 (HSV-1) is the only FDA- and EMA- approved oncolytic virus, and accordingly, many potential oncolytic HSVs (oHSV) are in clinical development. The utilized oHSV parental strains are, however, mostly based on laboratory reference strains, which may possess a compromised cy...

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Autores principales: Kalke, Kiira, Orpana, Julius, Lasanen, Tuomas, Esparta, Olaya, Lund, Liisa M., Frejborg, Fanny, Vuorinen, Tytti, Paavilainen, Henrik, Hukkanen, Veijo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9230972/
https://www.ncbi.nlm.nih.gov/pubmed/35746761
http://dx.doi.org/10.3390/v14061290
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author Kalke, Kiira
Orpana, Julius
Lasanen, Tuomas
Esparta, Olaya
Lund, Liisa M.
Frejborg, Fanny
Vuorinen, Tytti
Paavilainen, Henrik
Hukkanen, Veijo
author_facet Kalke, Kiira
Orpana, Julius
Lasanen, Tuomas
Esparta, Olaya
Lund, Liisa M.
Frejborg, Fanny
Vuorinen, Tytti
Paavilainen, Henrik
Hukkanen, Veijo
author_sort Kalke, Kiira
collection PubMed
description Herpes simplex virus type 1 (HSV-1) is the only FDA- and EMA- approved oncolytic virus, and accordingly, many potential oncolytic HSVs (oHSV) are in clinical development. The utilized oHSV parental strains are, however, mostly based on laboratory reference strains, which may possess a compromised cytolytic capacity in contrast to circulating strains of HSV-1. Here, we assess the phenotype of thirty-six circulating HSV-1 strains from Finland to uncover their potential as oHSV backbones. First, we determined their capacity for cell-to-cell versus extracellular spread, to find strains with replication profiles favorable for each application. Second, to unfold the differences, we studied the genetic diversity of two relevant viral glycoproteins (gB/UL27, gI/US7). Third, we examined the oncolytic potential of the strains in cells representing glioma, lymphoma, and colorectal adenocarcinoma. Our results suggest that the phenotype of a circulating isolate, including the oncolytic potential, is highly related to the host cell type. Nevertheless, we identified isolates with increased oncolytic potential in comparison with the reference viruses across many or all of the studied cancer cell types. Our research emphasizes the need for careful selection of the backbone virus in early vector design, and it highlights the potential of clinical isolates as backbones in oHSV development.
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spelling pubmed-92309722022-06-25 The In Vitro Replication, Spread, and Oncolytic Potential of Finnish Circulating Strains of Herpes Simplex Virus Type 1 Kalke, Kiira Orpana, Julius Lasanen, Tuomas Esparta, Olaya Lund, Liisa M. Frejborg, Fanny Vuorinen, Tytti Paavilainen, Henrik Hukkanen, Veijo Viruses Article Herpes simplex virus type 1 (HSV-1) is the only FDA- and EMA- approved oncolytic virus, and accordingly, many potential oncolytic HSVs (oHSV) are in clinical development. The utilized oHSV parental strains are, however, mostly based on laboratory reference strains, which may possess a compromised cytolytic capacity in contrast to circulating strains of HSV-1. Here, we assess the phenotype of thirty-six circulating HSV-1 strains from Finland to uncover their potential as oHSV backbones. First, we determined their capacity for cell-to-cell versus extracellular spread, to find strains with replication profiles favorable for each application. Second, to unfold the differences, we studied the genetic diversity of two relevant viral glycoproteins (gB/UL27, gI/US7). Third, we examined the oncolytic potential of the strains in cells representing glioma, lymphoma, and colorectal adenocarcinoma. Our results suggest that the phenotype of a circulating isolate, including the oncolytic potential, is highly related to the host cell type. Nevertheless, we identified isolates with increased oncolytic potential in comparison with the reference viruses across many or all of the studied cancer cell types. Our research emphasizes the need for careful selection of the backbone virus in early vector design, and it highlights the potential of clinical isolates as backbones in oHSV development. MDPI 2022-06-13 /pmc/articles/PMC9230972/ /pubmed/35746761 http://dx.doi.org/10.3390/v14061290 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Kalke, Kiira
Orpana, Julius
Lasanen, Tuomas
Esparta, Olaya
Lund, Liisa M.
Frejborg, Fanny
Vuorinen, Tytti
Paavilainen, Henrik
Hukkanen, Veijo
The In Vitro Replication, Spread, and Oncolytic Potential of Finnish Circulating Strains of Herpes Simplex Virus Type 1
title The In Vitro Replication, Spread, and Oncolytic Potential of Finnish Circulating Strains of Herpes Simplex Virus Type 1
title_full The In Vitro Replication, Spread, and Oncolytic Potential of Finnish Circulating Strains of Herpes Simplex Virus Type 1
title_fullStr The In Vitro Replication, Spread, and Oncolytic Potential of Finnish Circulating Strains of Herpes Simplex Virus Type 1
title_full_unstemmed The In Vitro Replication, Spread, and Oncolytic Potential of Finnish Circulating Strains of Herpes Simplex Virus Type 1
title_short The In Vitro Replication, Spread, and Oncolytic Potential of Finnish Circulating Strains of Herpes Simplex Virus Type 1
title_sort in vitro replication, spread, and oncolytic potential of finnish circulating strains of herpes simplex virus type 1
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9230972/
https://www.ncbi.nlm.nih.gov/pubmed/35746761
http://dx.doi.org/10.3390/v14061290
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