Human cytomegalovirus: demonstration of permissive epithelial cells and nonpermissive fibroblastic cells in a survey of human cell lines

Abstract

To more clearly define the characteristics which render a cell permissive for human cytomegalovirus (HCMV), we screened a panel of human cell lines differing in morphology, ploidy, and extent of differentiation for the ability to sustain productive HCMV replication. Cells were exposed to HCMV at 5 to 20 PFU per cell and examined at 4 to 14 days postinfection to detect the production of infectious virus by a plaque assay and the assembly of progeny virions by electron microscopy. By these criteria, high-titer HCMV replication (10(6) to 10(7) PFU/ml) occurred in a well-differentiated, diploid, epithelial cell line, HCMC, which had been derived from normal human colonic mucosa. In contrast, all aneuploid human cell types proved to be nonpermissive, including a fibroblastic cell line designated HT-144. These results indicate that HCMV replication in cultures is not strictly limited to fibroblasts and conversely that not all human fibroblastic cells are permissive for HCMV. Nonpermissive cell types were further investigated by attempts to chemically induce HCMV replication. Treatment of nonpermissive cell types with 25 to 500 micrograms of 5-iodo-2'-deoxyuridine per ml prior to infection did not convert them to the permissive state. The implications of these findings for the possible mechanisms maintaining the nonpermissive state are discussed.