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Monocyte-derived dendritic cells are permissive to the complete replicative cycle of human cytomegalovirus
S Riegler1, H Hebart, H Einsele
1Department of Medical Virology, University of Tübingen, Calwerstrasse 7/6, D-72076 Tübingen, Germany.
Abstract:
The susceptibility of monocyte-derived immature dendritic cells (DC) to infection by various strains of human cytomegalovirus (HCMV) was analysed. Immature DC were generated by incubation of peripheral blood monocytes with interleukin-4 and granulocyte-macrophage colony-stimulating factor for 7 days and were characterized by a CD1a+/CD40+/CD80+/CD86+/HLA-DR+/CD14- phenotype. Viral antigen expression and production of infectious progeny virus were analysed in infected immature DC cultures. Immature DC were 80-90 % susceptible to HCMV strains that had been propagated in endothelial cell culture, whereas the infection rate was negligible with fibroblast-adapted HCMV strains. Immature DC infection resulted in expression of viral immediate early, early and late genes. Productive infection was proven by the detection of infectious virus in single-step growth curves and in infectious centre assays. It is concluded that HCMV might interfere with the host immune reaction by permissive, lytic infection of immature DC.
Insights
Human cytomegalovirus (HCMV) productively infects immature dendritic cells (DC), which are key immune cells. This permissive, lytic infection of DC by HCMV may impact the host immune response.
Area of Science:
- Immunology
- Virology
- Cell Biology
Background:
- Dendritic cells (DC) are crucial for initiating immune responses.
- Human cytomegalovirus (HCMV) is a widespread pathogen with complex interactions with the immune system.
- The susceptibility of immature dendritic cells to HCMV infection is not fully understood.
Purpose of the Study:
- To investigate the susceptibility of monocyte-derived immature dendritic cells (DC) to infection by different strains of human cytomegalovirus (HCMV).
- To characterize the nature of HCMV infection in immature DC, including viral gene expression and progeny production.
Main Methods:
- Immature DC were generated from peripheral blood monocytes using interleukin-4 and granulocyte-macrophage colony-stimulating factor.
- Cells were infected with various HCMV strains, and susceptibility was assessed.
- Viral antigen expression, viral gene expression (immediate early, early, late), and infectious progeny production were analyzed.
Main Results:
- Immature DC showed high susceptibility (80-90%) to HCMV strains propagated in endothelial cells.
- Fibroblast-adapted HCMV strains exhibited negligible infection rates in immature DC.
- HCMV infection led to the expression of viral immediate early, early, and late genes within immature DC.
- Productive infection was confirmed through single-step growth curves and infectious center assays, demonstrating the release of infectious virus.
Conclusions:
- Immature dendritic cells are highly susceptible to productive, lytic infection by HCMV strains derived from endothelial cells.
- HCMV may evade or manipulate host immune responses through permissive infection of immature dendritic cells.
- These findings highlight a potential mechanism for HCMV persistence and immune modulation.