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Involvement of the Nucleolus in Viral Synthesis in the Cells of Primary Renal Tumors of Leopard Frogs¹

M. R. C. Epigenetics Laboratory, Department of Animal Genetics, University of Edinburgh, Edinburgh 9, Scotland

This electron microscope study of primary Lucké tumors with demonstrable viruses shows that striking nucleolar alterations occur in the cells of the tumor. These changes seem to be related to the synthesis of the virus. The structure of the nucleolus in "normal" cells of the tumor is not unlike that found in many vertebrate cells. The earliest nucleolar alteration is a redistribution of the fibrillar region. In a further series of changes, the fibrillar zones enlarge (while the particulate regions disperse) and are transformed into large electron-dense clumps. At the stage when the clumps are fragmented, various viral particles become evident in the nucleus. It is therefore inferred that the materials of the clumps or their dissolution products are prerequisite to viral replication. Morphologic observations also suggest that viral nucleoids or similar bodies begin to form in intimate association with the scattered clump fragments. No preferential site of formation of the viral capsids has been noted. The proposed sequence of nucleolar events leading to viral replication remains to be tested by experimental methods.

In the light of information now available, an explanation is presented to account for nucleolar involvement in the replication of both DNA and RNA viruses. It is hoped that the theory outlined will give impetus for future research in this area.

¹ This research was supported by the Damon Runyon Memorial Fund for Cancer Research and the British Empire Cancer Campaign for Research.

Received 12/12/67. Accepted 5/ 1/68.