Evaluation of the antitumor effects of Herpes simplex virus lacking ribonucleotide reductase in a murine retinoblastoma model

Abstract

Purpose. To determine if an attenuated herpes simplex virus (HSV) lacking the large subunit of ribonucleotide reductase has antitumor effects in a transgenic mouse model of retinoblastoma (LHβTAg). Methods. LHβTAg mice were injected ocularly with 1 × 10⁶ pfu of the hrR3 virus and tumor sizes were measured 3 weeks later. Replication of the virus in the eye and cultured murine retinoblastoma cells was tested by titration. Distribution of the virus in tumor was measured by X-gal staining. Results. Intraocular injection of mice with hrR3 (n = 24) did not result in a significant reduction in tumor size compared to uninjected (n = 24) or PBS injected controls (n = 16). Neither the hrR3, nor the HSV RE6 mutant, which was previously shown to have antitumor effects in vivo, replicated in cultured murine tumor cells in vitro, compared to wild-type HSV. The hrR3 virus also did not replicate significantly in tumor cells in vivo, compared to normal eye tissue. Conclusions. These results suggest that mutant HSV lacking ribonucleotide reductase do not display oncolytic activity in the LHβTAg mouse and that this model may not be suitable for studying viral oncolysis as a therapy for retinoblastoma.

• retinoblastoma
• Herpes simplex virus
• ribonucleotide reductase
• LHβTAg mouse