Virus replication in infected epithelial cells is coupled to cell shape-responsive metabolic controls.

The cell shape of monkey epithelial cells was varied from flat to spheroidal by gradually reducing the substrate adhesiveness with poly (HEMA) films of increasing thickness. The decrease in cell spreading is accompanied by a dramatic response in cellular macromolecular metabolism in the nucleus. Within 14 to 16 hr, DNA and RNA syntheses are inhibited by more than 95%, while the level of protein synthesis is reduced by only twofold after 24 hr in spheroidal-suspension culture. When epithelial cells, spread to various degrees, are infected with SV40 or herpes virus a parallel inhibition of virus replication and cellular macromolecular metabolism occurs. However, VSV can proliferate in the metabolically active cytoplasm of epithelial cells in which nuclear activity is inhibited owing to alterations in cell shape. The results suggest that the metabolic restrictions imposed on epithelial cells, owing to changes in cell spreading, are a dominant phenomenon that cannot be overcome by virus infection. Rather, virus replication, which is dependent on the cellular metabolic machinery, is inhibited in parallel with the inhibition of cellular macromolecular metabolism.