Figure 5

AV reovirus remains oncolytic in vivo and shows reduced toxicity. (A) HTR1, Raji PI and CA46 PI cells were injected into the left flanks of SCID mice, which were photographed after 3–4 weeks and as morbidity developed. All Raji PI- and CA46 PI- treated mice developed black tails at 22–25 days post-injection (center and right panels) and were killed shortly thereafter; whereas HTR1-treated mice displayed no signs of distress after 4 weeks (left panel) and only began to develop black tails at 3–7 months post-injection. (B) Severe combined immunodeficiency mice received single implantations of 5 × 10⁶ HCT116 colon carcinoma or HT1080 fibrosarcoma cells. At 11 days after implantation, palpable tumours were injected with WT, AV or UV-inactivated (Dead; D) reoviruses at 10⁷ PFU/tumour and tumour growth was followed up to 34 days post-implantation. WT reovirus was reinjected 23 days post-implantation and AV reovirus was reinjected 23 and 27 days post-implantation. (C) Histological comparison of HCT116 and HT1080 tumours and heart tissue from SCID mice treated with reoviruses (WT, AV and D reovirus as above). Paraffin sections of reovirus-treated tumours (24 days post-infection) were analysed by indirect immunohistochemical staining using reovirus antiserum; brown staining represents reoviral antigen positive regions (upper panels). Paraffin sections of heart tissue from reovirus-injected mice (23 days post-infection) were analysed by H&E (middle panels) and indirect immunohistochemical staining (lower panels) using reovirus antiserum. Extensive necrotic lesions (arrows) and massive lymphocyte infiltration were observed in heart tissue from WT reovirus-infected mice, but not AV virus-treated mice (middle panel). Wild-type reovirus infected mice also showed reoviral antigen-positive regions (arrows; lower panel); sections were counter-stained with methyl green.