Herpes-Type Virus Recovery from "Virus-Free" Frog Kidney Tumors

Abstract

Spontaneous renal adenocarcinomas of Rana pipiens exist in two seasonal forms within the same populations of northern United States frogs. Tumors from animals collected in winter monlths display negligible mitotic activity and contain numerous cells characterized by enlarged nuclei with marginated chromatin and Cowdry (1) type A inclusions. A constant association of herpes-type virus with inclusion-conltaining cells has been demonstrated by electron microscopic studies of these naturally occurring winter tumors (2,3). In contrast, tumors from summer frogs are mitotically aotive and lack viral inclusioncontaining cells. These observations have led to the postulation of suggested life cycles for the Luck6 frog tumor (4) and for its associated virus ( 5 ) .This tumor dichotomy appears to be a temperature-related phenomenon: tumors arising in laboratory-housed frogs, regardless of season, display "summer" morphology when host animah are maintained at 2&26OC, or "winter" morphology when maintained at 5°C (6). The dependence of winter tumor m rphology upon low temperature was further substantiated by studies in which tumors with typical " s u m w " morphology developed "winter" characteristics (including intranuclear inclusions) after the tumor-bearing frogs had been maintained at 4OC for several months (7).In the present study "virus-free" primary tumors and eye chamber transplants from these tumors were subjected to prolonged low temperature treatment. Herpes-type virus developed both in primary tumors and in transplants, and herpesvirus was recovered from primary tumor.

Oncogenic herpesvirus infections of animals

“…Rafferty (1965) showed that intranuclear inclusions developed in tumours which were free of such inclusions several months after the environment of the host frogs was changed to a temperature of 4°C. Similar results were obtained by Mizell, Stackpole, and Halperen (1968), and this latter group extended their study to show that virus particles as well as inclusions appeared in tumours, previously free of particles and inclusions, which had been transferred to the anterior chamber of the eye of Rana pipiens and other species of frog and subsequently kept at 7 5°C (Mizell et al, 1968;Mizell, Stackpole, and Isaacs, 1969). More recently organ cultures of tumours without inclusions have been shown to develop inclusions when the cultures were held at 9°C (Morek and Tweedell, see Granoff, 1972).…”

Neoplasia in Poikilotherms

“…These were present both in the nucleus and in the cytoplasm, always associated with inclusion bodies, and were found only in frogs that had been captured during winter. Temperature sensitivity of the virus has been demonstrated by transplantation of summer tumor fragments in the anterior chamber of the eye of leopard frogs known not to carry the virus and maintaining them at a temperature of 7 .5°C, whereupon virus particles developed in the tumor implants (Mizell et al, 1968. The activation of previously latent virus in summer tumor tissue has also been accomplished in vitro with tumor fragments incubated at 7 .5°C on agar slants (Breidenbach etal., 1971).…”

Defective Dna Animal Viruses

“…Prolonged low temperatures favored the production of both; thus, tumors from frogs captured in the winter and spring more frequently contained inclusions and virus particles. If frogs bearing primary virus-free tumors were kept for prolonged periods at low temperatures, the herpesvirus particles appeared in the tumor cells (44). Granoff and his co-workers isolated a virus, FV-l, from the frog tumor cells which was unable to replicate at 33°C although replication occurred at 24°C (45).…”