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Nucleolar Changes in KB Tumor Cells Infected with Herpes Simplex Virus

Department of Pathology of the National Cancer Institute, and Laboratory of Electron Microscopy, Fondazione Carlo Erba, Milan, Italy

Cultures of KB tumor cells were infected with herpes simplex virus [Bruxelles strain, infectious titer 2 x 10⁶/ml tissue culture infecting dose (TCID₅₀)], and the resulting alterations were studied by electron microscopy.

Peculiar lesions involve the nucleolus. In the cells containing only a few immature virus particles in the nucleus, the nucleolar ribosomes, the nonribosomic RNA filaments, and the amorphous nucleolar component segregate and coalesce to form round aggregates. Sometimes the fibrillar component seems to "cap" the mass of the closely-grouped nucleolar ribosomes.

In the cells containing a greater number of virus particles, both in the nucleus and in the cytoplasm, the nucleolar substances aggregate and become more compact and electron dense. The nucleolus decreases gradually in size until it fragments.

The earliest cytoplasmic change takes place as soon as the 1st immature virus particles appear in the nucleus, and consists of a decrease in ribosomes and polysomic chains. At more advanced stages of viral invasion of the cell, numerous myelinic figures and other nonspecific degenerative lesions appear in the cytoplasm, preceding cellular lysis.

The ultrastructural changes of the nucleolus and the reduction in polysomic chains are very similar to the alterations induced in the cells by actinomycin D, mitomycin C, and 4-nitroquinoline-N-oxide.

Received 6/ 9/66. Accepted 9/23/66.

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