Related Experiment Videos
Human cytomegalovirus replication and modulation of apoptosis in astrocytes
J R Lokensgard1, M C Cheeran, G Gekker
1Institute for Brain and Immune Disorders, Minneapolis Medical Research Foundation, Minnesota 55404, USA. jlokensg@biosci.cbs.umn.edu
Objectives:
To characterize replication patterns and cytopathic effects during human cytomegalovirus (HCMV) infection of brain cells.
Design:
Primary human mixed glial/neuronal cells, as well as purified microglial, astroglial, and enriched neuronal cell cultures, were infected with HCMV strains AD169 and RC256 to determine the ability of the different brain cell types to support viral replication.
Results:
Mixed glial/neuronal cell cultures were fully permissive for viral replication. Based on previous studies, we hypothesized that human microglial cells would preferentially support productive HCMV replication. However, HCMV did not replicate or display genomic expression in microglial cells. In contrast, primary astrocytes were fully permissive and displayed HCMV-induced cytopathic effects resulting in cell death. In highly enriched neuronal cultures, productive infection and viral expression occurred only in scattered astrocytes. Early in the infection, apoptotic plasma membrane changes were induced in astrocytes. However, nuclear fragmentation was not apparent until later during the course of infection.
Conclusions:
These results suggest that HCMV possesses astrocytotropic properties that confer preferential expression and cytopathic replication in astrocytes over microglia or neuronal cells. Apoptotic cell death, which is a result of HCMV infection, appears to be delayed until peak viral replication has occurred.
Insights
Human cytomegalovirus (HCMV) preferentially infects astrocytes, not microglia, in the brain. HCMV replication in astrocytes causes delayed cell death after peak viral activity.
Area of Science:
- Neurovirology
- Cellular Biology
Background:
- Human cytomegalovirus (HCMV) is a common pathogen with diverse effects.
- Brain cell tropism of HCMV is not fully understood, particularly regarding glial and neuronal cells.
Purpose of the Study:
- To investigate HCMV replication patterns and cytopathic effects in different human brain cell types.
- To determine the susceptibility of astrocytes, microglia, and neurons to HCMV infection.
Main Methods:
- Primary human mixed glial/neuronal, microglial, astroglial, and neuronal cultures were infected with HCMV strains AD169 and RC256.
- Viral replication, genomic expression, and cytopathic effects were analyzed in each cell type.
Main Results:
- HCMV replicated productively in mixed glial/neuronal and primary astrocyte cultures, causing cytopathic effects and cell death.
- HCMV did not replicate or show genomic expression in microglial cells.
- In neuronal cultures, infection was limited to scattered astrocytes, with delayed nuclear fragmentation observed after initial apoptotic changes.
Conclusions:
- HCMV exhibits astrocytotropic properties, favoring replication and cytopathic effects in astrocytes over microglia and neurons.
- Apoptotic cell death in infected astrocytes is delayed until after peak viral replication.