One virus two kills: Bovine herpes virus-4 infection of canine osteosarcoma and histiocytic sarcoma cells showed oncolytic properties in vitro

Introduction Canine osteosarcoma(c-OSA) and histiocytic sarcoma (c-HS) represent tumors with a poor prognosis and poor response to conventional therapies. A promising new alternative approach can be represented by viral oncolysis. Bovine herpesvirus 4 (BoHV4) is a promising candidate for oncolytic viral therapy, thanks to its safety, its ability to replicate in canine cell lines and its oncolytic potential in human glioma and carcinoma cell lines. The aim of the present study was to demonstrate that BoHV-4 is a good candidate for viral oncolysis in veterinary medicine.

Material and methods Infected (BoHV-4-GFPΔTK) and non-infected primary canine fibroblasts, c-OSA primary cell lines (OSA2), continuous c-OSA (D17) and c-HS (DH82) cell lines were comparatively investigated in vitro. Immunofluorescence, western blot and flow cytometry were used for MOI assessment, and the quantification of the percentage of infected cells and cell death over time.

Results BoHV-4-GFPΔTK successfully infected c-OSA and c-HS cell lines at a lower MOI than normal canine fibroblasts at same time points. BoHV-4-GFPΔTK infection induced a cytopathic effect in a dose- and time-dependent manner. At 0.5 and 1 MOI the virus is inducing a prominent cytopathic effect on c-OSA and c-HS cell lines, with minimal infection and damage on normal canine fibroblasts.

Conclusions This preliminary assessment of the oncolytic potential of BoHV-4 proves it to be a good candidate for further investigations about its oncolytic potential and to study the mechanism by which it induces cell death.

Publication History

Article published online:
13 June 2025