The Journal of Infectious Diseases · 1995 · 128 citations · 60 references
Infectious CytomegalovirusViral PersistenceInfectionCmv-infected EcEndothelial CellsViral PathogenesisImmunologyAntiviral ResponseVirologyProblematic VirusVirus-host InteractionChronic Viral InfectionImmunotherapyMedicineCell TransplantationVascular Endothelial CellsBidirectional Transmission
Cytomegalovirus infects diverse tissues, but how it disseminates remains unclear, with hematogenous spread suggested yet peripheral blood mononuclear cells not fully supporting viral replication in vitro. The study tested whether peripheral blood mononuclear cells could be productively infected through contact with CMV‑infected endothelial cells by coculturing them with infected endothelial monolayers. Infected monocytes were isolated from endothelial layers, replated, and then overlaid with fresh endothelial cells to assess their ability to transmit infectious virus. Up to 30 % of monocytes adhered to endothelial cells were infected, and when replated and overlaid with fresh endothelial cells they produced CMV‑positive cytopathic foci, demonstrating that monocytes can transmit infectious virus and underscoring an interactive role of endothelium and monocytes in CMV dissemination.
Cytomegalovirus (CMV) infects multiple tissues and organs; however, mechanisms of dissemination remain elusive. Although hematogenous spread has been implicated, in vitro studies have generally indicated that peripheral blood mononuclear cells (PBMC) do not support the complete viral reproductive cycle. Since CMV infects endothelial cells (EC), the hypothesis that PBMC can be productively infected by contact with CMV-infected EC was tested by coculturing PBMC with CMV-infected endothelial monolayers. Dual immunohistochemical staining for mononuclear cell markers and CMV-specific antigens demonstrated infection of up to 30% of monocytes adhering to EC. To determine if infected monocytes could transmit infectious virus, they were separated from EC, replated in culture wells, and then overlaid with fresh EC. The subsequent appearance of CMV-positive cytopathic foci within the overlaid monolayers indicated that these monocytes were capable of transmitting infectious virus. Thus, these results support an interactive role for the endothelium and circulating monocytes in the dissemination of this clinically problematic virus.
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T Maciag, J Cerundolo, S Ilsley et al. · Proceedings of the National Academy of Sciences · 1979 · 716 citations · Full text
Endothelial Cell Pathobiology, Animal Physiology, Developmental Biology +15