Human cytomegalovirus infection of kidney glomerular visceral epithelial and tubular epithelial cells in culture.

Evidence suggests that human cytomegalovirus is resident in the kidneys of seropositive donors at the time of transplantation, and CMV has been implicated in both glomerulonephritis and interstitial nephritis. In this study we assessed the interactions of CMV with two human renal cell types in culture: glomerular visceral epithelial cells (GVE) and renal tubular epithelial (RTE) cells. GVE permitted viral adsorption, penetration, nuclear translocation, and restricted viral transcription. However, early viral protein expression was not detectable by immunofluorescence and infectious virions were not produced. In contrast, retinoic acid-treated GVE permitted early viral protein expression and supported CMV replication. RTE also permitted viral adsorption and penetration. CMV-specific early proteins were readily observed by immunofluorescence, and CMV DNA replication was observed by DNA dot blot hybridization. Assays comparing viral yield with viral DNA synthesis indicated that RTE were capable of supporting persistent and prolonged viral expression without significant cell death for at least 55 days after infection. We believe that these findings should explain chronic viruria in individuals with symptomatic and asymptomatic CMV infection. In addition, GVE could also be a potential source of CMV transmission when altered by disease or transplantation.

Cytomegalovirus replicates efficiently in human kidney mesangial cells.

Human cytomegalovirus (HCMV) is a major renal pathogen in congenitally infected infants and renal allograft recipients. We postulated that a specific renal cell type was involved in HCMV infection and reactivation. Human fetal kidney cortex cell cultures were assayed for their ability to support HCMV infection. Infectious center assays indicated that the low level of viral replication observed by virus yield assay occurred from a fraction of the cells in the mixed cultures. Virus-specific immunofluorescence and in situ hybridization documented the presence of HCMV-specific protein and nucleic acid, respectively, in a morphologically distinct cell type. These cells were purified, were identified as kidney mesangial cells, and were observed to support efficient HCMV replication. Our research identifies mesangial cells as a renal cell type that supports HCMV replication and provides evidence to implicate these cells in the pathogenesis of HCMV-induced renal disease.