The susceptibility of Tupaia belangeri (tree shrews, which are primitive prosimian primates) to infection with herpes simplex virus (HSV) and the pathogenesis of HSV in these animals were investigated. Juvenile (28--45 days old) and adult (150 days old) animals were inoculated intravenously, intraperitoneally, or subcutaneously with HSV type 1 or 2 (25--10(5) plaque-forming units per animal). Clinical illness usually appeared in juvenile animals on the second day after inoculation, and the animals died between two and 14 days after inoculation. High titers of infectious HSV were recovered from liver and spleen. The histopathologic examination always showed severe liver changes with numerous necrotic areas. The morphologic events in the liver were designated as herpetic hepatitis. The next most common morphologic findings were encephalitis and fibrosis in the spleen. These results demonstrate the high pathogenicity of HSV types 1 and 2 in juvenile T. belangeri. In contrast, adult animals did not develop acute clinical disease and survived the HSV infection.

Somatic cell hybrids between the malignant Burkitt lymphoma cell line BL 60 and the non-malignant Epstein-Barr virus (EBV) immortalized lymphoblastoid cell line (LCL) IARC 277 demonstrate the deregulated c-myc transcription pattern of the parental BL cell line during exponential growth in tissue culture. Subcutaneous nude mouse grafts of these hybrids, however, completely regress after an initial growth phase. To investigate whether regression of these grafts is mediated by a down-regulation of the BL-60-derived deregulated c-myc gene in vivo, c-myc transcription was analyzed in growing versus regressing hybrid grafts. In the initial growth phase as well as during regression, these grafts showed the deregulated c-myc expression pattern of the parental BL cell line with highly abundant c-myc transcripts originating from the BL specific translocation chromosome 8q+. Our results question the significance of c-myc deregulation for an unlimited in vivo growth potential of B-lymphoblastoid cells. To further characterize the hybrids, surface expression of B-cell-specific antigens was analyzed on the hybrids and shown to correspond to that of the parental LCL. In addition, transcription of the gene encoding for the EBV latent membrane protein (LMP) as well as histological features were analyzed in growing versus regressing hybrid grafts. The LMP gene, which is down-regulated in the tumors produced by the parental BL cells, was expressed in the hybrid grafts as well as in the parental LCL grafts. This finding might be compatible with a host response of the nude mouse against LMP. The histological analysis, however, which revealed massive necrosis in the center of the regressing grafts without pronounced inflammatory infiltrates, rather points to a hypoxemic process leading to graft regression.

The surface morphology of herpes simplex virus transformed cells was examined by scanning electron microscopy in exponentially growing and density inhibited rat embryo fibroblast cultures. The cell surface of oncogenically-transformed cells became more villated and many microvilli showed branching. C-type virus particles budding from the cell surface were commonly observed. Virus induced cytopathic effects observed by scanning electron microscopy, included rounding up and detachment of degenerating cells from the substrate.

No abstract