Human cytomegalovirus causes productive infection and neuronal injury in differentiating fetal human central nervous system neuroepithelial precursor cells

J Hum Virol. Jul-Aug 2000;3(4):215-28.

Abstract

Objectives: To study the effect of cell differentiation on the vulnerability of human neural cell types to human cytomegalovirus (HCMV) infection.

Study design/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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Apoptosis
  • Astrocytes
  • Brain / cytology
  • Brain / embryology*
  • Cell Differentiation
  • Cells, Cultured
  • Cytomegalovirus / pathogenicity*
  • Cytomegalovirus / physiology*
  • Cytopathogenic Effect, Viral
  • Epithelial Cells / cytology
  • Epithelial Cells / physiology
  • Epithelial Cells / virology*
  • Female
  • Fetus / cytology
  • Humans
  • Neurons / cytology
  • Neurons / physiology
  • Neurons / virology*
  • Pregnancy
  • Pregnancy Trimester, First
  • Stem Cells / cytology
  • Stem Cells / physiology
  • Stem Cells / virology*