Human cytomegalovirus causes productive infection and neuronal injury in differentiating fetal human central nervous system neuroepithelial precursor cells.
OBJECTIVE
To study the effect of cell differentiation on the vulnerability of human neural cell types to human cytomegalovirus (HCMV) infection.


METHODS
Primary cultures of human fetal neuroepithelial stem cells and differentiating neuroepithelial precursor cells were infected with HCMV strain AD169. Infectious virus production, apoptosis, and viral-associated cytopathic effects then were examined over a 5-day period.


RESULTS
HCMV established productive infection in these cells, generating 10-fold amplification of infectious virus. There was no significant difference in the percentage of apoptotic cells in HCMV-infected versus mock-infected cultures. HCMV antigen and specific cytopathic effects were observed in differentiating astrocytes and neurons, although HCMV antigen was 2-fold more frequent among postmitotic neurons.


CONCLUSIONS
Neuroepithelial precursor cells and differentiating astrocytes and neurons are permissive to cytopathic HCMV infection, suggesting that the fetal human central nervous system is vulnerable to HCMV-induced neuronal injury at its earliest stages of development.
McCarthy
M
M
Department of Veterans Affairs Medical Center, Miami, Florida 33125, USA. mmccarth@med.miami.edu
Auger
D
D
Whittemore
S R
SR
D017209:Apoptosis; D001253:Astrocytes; D001921:Brain / Q000166:cytology / Q000196:embryology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D003587:Cytomegalovirus / Q000472:pathogenicity* / Q000502:physiology*; D003588:Cytopathogenic Effect, Viral; D004847:Epithelial Cells / Q000166:cytology / Q000502:physiology / Q000821:virology*; D005260:Female; D005333:Fetus / Q000166:cytology; D006801:Humans; D009474:Neurons / Q000166:cytology / Q000502:physiology / Q000821:virology*; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D013234:Stem Cells / Q000166:cytology / Q000502:physiology / Q000821:virology*