Characteristics of human arterial smooth muscle cell cultures infected with cytomegalovirus

Abstract

Distinct, sequential events occurring during the destruction and simultaneous regrowth of human arterial smooth muscle cell (SMC) cultures infected with cytomegalovirus (CMV, AD169 strain) were characterized. The events were influenced by the typical phenotypic diversity reflecting relative states of differentiation of the SMC cultures. Progenitors of regeneration were a surviving population of small, undifferentiated or relatively undifferentiated SMCs. As these cells reached confluence focally, the number of cells reactive with antismooth muscle serum, i.e. differentiating, increased, and in some postconfluent foci the organization of SMCs resembled the topography of uninfected cultures. Thus, infected SMC cultures had a limited capacity to repopulate, to organize typically, and to differentiate. However, continuing cytopathic effects gradually destroyed much of the regrowth, and a relatively large, nondividing SMC with prominent cytoplasmic filaments, similar to SMCs in terminal, uninfected cultures, predominated. Infected cultures consisting overwhelmingly of the large terminal phenotype were far less productive of infectious CMV than cultures populated by SMCs with continuing capacity to divide. Gradually, cultures consisting of the terminal phenotype deteriorated as a result of sporadic cytopathic effects of CMV and an effect resembling "senescent" degeneration in uninfected, nondividing cultures in late passage. The infected, terminal phenotype could be a latent or persistent source of CMV antigen or nucleic acid-positive cells detected by different investigators in normal and in atheromatous, human tissue, assuming that it exists and survives for an extended period in vivo after infection of vascular SMC.

Rat cytomegalovirus replication in the salivary glands is exclusively confined to striated duct cells

“…These factors include the type of cell that is infected and the immune response of the host to this infection. Depending on the type of cell that is infected, an infection results in cell death (fibroblasts [11]), an abortive infection (endothelial cells [9]) or a persistent infection (smooth muscle cells and monocytes/macrophages [48,21])…”

Human Cytomegalovirus Cell Tropism and Pathogenesis

“…Besides skin fibroblasts and lung fibroblasts, permissive infection by HCMV has also been demon strated in bone marrow fibroblasts [85,86], Other mesen chymal cells such as vascular smooth muscle cells and endothelial cells are also susceptible to HCMV infection in culture. After infection with HCMV laboratory strain AD 169, human arterial smooth muscle cells expressed IE antigen, developed a cytopathogenetic effect and released infectious virus [76,87], The infection of vascular smooth muscle cells has been suggested to be involved in the pathogenesis of atherosclerosis [64], This has been em phasized by a recent publication that demonstrated a cor relation of HCMV DNA and the tumor suppressor anti gen p53 in tissues from restenosis after coronary angio plasty [88]. The [74.…”

“…Lytic infec tion has been demonstrated in permissive cell culture sys tems including fibroblasts, endothelial cells, macro phages, and smooth muscle cells [72][73][74]76]. In vivo, extensive viral replication has been observed within in fected organs, and late-stage infected cells displayed mor phological alterations known from lytically infected cul tured cells [29.…”

Lysis of Human Arterial Smooth Muscle Cells Infected with Herpesviridae by Peripheral Blood Mononuclear Cells: Implications for Atherosclerosis

“…The effect of CMV on SMC cultures is comparatively delayed and prolonged, resulting in extended survival of a fraction of the starting cell population (21). CMV infection in SMC cultures probably persists through limited, temporary reconstitution of the cultures (22). In this study, we report natural killing of SMC and of MRC-5 cells infected with CMV or HSV by PBMC.…”