Distribution of viral and cellular markers in the brain of rats following glioma injection with H-1PV. Panel 1: PCR detection of H-1PV DNA (A and B) and RNA (C). The presence of H-1PV DNA in the treated tumor, adjacent brain tissue (peritumoral), contralateral hemisphere, and cerebellum (as indicated) was determined by PCR 48 hours (A) or 72 hours (B) after intratumoral virus injection. The production of H-1PV transcripts at the same locations was tested by RT–PCR 72 hours after intratumoral injection of H-1PV (C). Amplified fragments were detected after agarose gel electrophoresis. The primers used anneal to exon sequences flanking a small intron, resulting in a slightly larger product amplified from DNA compared with intronless cDNA. pos, positive control (H-1PV plasmid DNA); neg, negative control (double-distilled water); far left lanes, size markers (DNA ladder). Panel 2: Immunohistochemical detection of parvoviral NS-1 proteins. Sections were prepared from RG-2 glioma and adjacent (brain) tissues, collected 2 days after intratumoral injection of 1.6 × 107 pfu of H-1PV. The fluorescence signal indicating the presence of NS-1 proteins is restricted to the tumor area and could not be detected in adjacent tissue (DAPI staining of nuclei on the same image). For orientation, H&E staining of the same brain area is shown at low and high magnification. Panel 3: Immunohistochemical detection of parvoviral NS-1 proteins in glioma tissue after iv injection. Sections were prepared 3 days after iv injection of 108 pfu of H-1PV. The green fluorescence demonstrates the parvoviral NS-1 protein scattered throughout the tumor tissue, proving that iv-administered H-1PV reached the brain tumor and is expressed. Panel 4: Impact of H-1PV infection on cathepsin B expression in RG-2 gliomas. An established RG-2 tumor was injected with H-1PV or mock-treated and removed 72 hours later for sectioning and immunohistochemical detection of cathepsin B. Virus infection correlated with a striking activation of cathepsin B, a known effector of H-1PV-induced glioma cell death. No cathepsin B signal was detected in mock infected tumors.