Replication of human cytomegalovirus in a rhabdomyosarcoma cell line depends on the state of differentiation of the cells

Abstract

The replication of human cytomegalovirus (HCMV) was investigated in a new human rhabdomyosarcoma cell line (KFR) with morphological and biochemical characteristics of fetal striated muscle precursors (rhabdomyoblasts). KFR cells exhibited the unique property for spontaneous morphological transformation from a poorly-differentiated state into well-differentiated (myotube-like) rhabdomyoblasts. The poorly-differentiated rhabdomyoblasts promoted both complete viral gene expression and the production of infectious virus. In contrast, in well-differentiated rhabdomyoblasts HCMV infection was abortive. The results showed that replication of HCMV in this human rhabdomyosarcoma cell line depended on the state of cellular differentiation.

Human Cytomegalovirus Infects Caco-2 Intestinal Epithelial Cells Basolaterally Regardless of the Differentiation State

“…Finally, it was reported that, in vitro, the efficiency of CMV replication seems to depend on the state of cellular differentiation (4,20). However, we showed here that infection with CMV of Caco-2 cells is independent of their state of differentiation.…”

“…Caco-2 cells differentiate spontaneously in culture (6,18), as they do in the normal intestine, and exhibit many of the morphologic and functional properties of enterocytes (28). The efficiency of CMV replication in other cell systems appears to depend on the state of differentiation of the cell (4,7,11,20). Thus, to examine the relationship of differentiation and infectibility, Caco-2 cultures grown on coverslips were infected 3, 6, and 14 days postseeding.…”

Human Cytomegalovirus Cell Tropism and Pathogenesis

“…This makes them an attractive object for the study of viral cell tropism. HCMV replication has been observed to depend on the state of cellular differentiation in monocytes/macrophages [72,96], in primary neurons [115], and in var ious cell lines including the teratocarcinoma cell line TERA-2 [78], the monocytic cell line THP-1 [79], the rhabdomyosarcoma cell line KFR [116], and the hemato poietic cell line TF1 [117], Expression from the major IE gene region has been found to be downregulated in nondifferentiated cells but can be induced when cells are treated with agents promoting differentiation [79,80], It is therefore assumed that the level of IE gene expression is critical for the progression of infected cells to the lytic replication cycle. In analogy, interstrain variabilities in the IE gene region might lead to differences in the host cell spectrum of various HCMV strains.…”

“…IFN-y and TNF-a were recently demonstrated to lift the block of MHC I expression to a degree that allows for CTL recognition to occur [222], As a mechanism of viral latency, limited viral gene expression in nonpermissive cell types has been suggest ed. This was mainly based on the finding that certain cells express only IE genes after infection with HCMV, but are permissive to the full replication cycle after differentia tion [72,78,79,96,[115][116][117], Interestingly, a selective interference with IE antigen presentation to cytotoxic T cells after HCMV infection has been reported in autolo gous human fibroblasts, while other viral antigens were readily presented in these cells [223], This suggests a mechanism by which cells restricted to IE gene expression might escape from the host's cytotoxic immune reaction. In vitro, differentiation-dependent viral gene expression has been demonstrated in a teratocarcinoma cell line [78] and in a monocytic cell line [79].…”

Long-term productive human cytomegalovirus infection of a human neuroblastoma cell line

“…Cultures of human teratocarcinoma cells were used to study features of HCMV infection of early embryonal cells (Gonczol et al, 1984). We showed that replication of HCMV in a human rhabdomyosarcoma cell line (KFR) depends on the state of cellular differentiation (Cinatl et al, 1994b). However, since HCMV does not shut down host-cell macromolecule synthesis (as does herpes simplex virus), infection of cells derived from embryonal tumours may be used to study the effects of HCMV infection on the differentiation properties of tumour cells.…”