A1 Refereed original research article in a scientific journal
The In Vitro Replication, Spread, and Oncolytic Potential of Finnish Circulating Strains of Herpes Simplex Virus Type 1
Authors: Kalke Kiira, Orpana Julius, Lasanen Tuomas, Esparta Olaya, Lund Liisa M., Frejborg Fanny, Vuorinen Tytti, Paavilainen Henrik, Hukkanen Veijo
Publisher: MDPI
Publication year: 2022
Journal: Viruses
Journal name in source: VIRUSES-BASEL
Journal acronym: VIRUSES-BASEL
Article number: 1290
Volume: 14
Issue: 6
Number of pages: 18
eISSN: 1999-4915
DOI: https://doi.org/10.3390/v14061290
Web address : https://www.mdpi.com/1999-4915/14/6/1290
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/175894444
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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