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

Micheline McCarthy, D. Auger, S. R. Whittemore

Research output: Contribution to journalArticle

43 Citations (Scopus)

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. (C) Lippincott Williams and Wilkins, Inc.

Original languageEnglish
Pages (from-to)215-228
Number of pages14
JournalJournal of Human Virology
Volume3
Issue number4
StatePublished - Jan 1 2000

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Neuroepithelial Cells
Cytomegalovirus
Central Nervous System
Wounds and Injuries
Infection
Cytomegalovirus Infections
Neurons
Astrocytes
Viral Cytopathogenic Effect
Fetal Stem Cells
Viruses
Antigens
Cell Differentiation

Keywords

  • Astrocytes
  • Cytomegalovirus
  • Herpesvirus infections
  • Neurons
  • Stem cells

ASJC Scopus subject areas

  • Virology

Cite this

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AU - Auger, D.

AU - Whittemore, S. R.

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N2 - 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. (C) Lippincott Williams and Wilkins, Inc.

AB - 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. (C) Lippincott Williams and Wilkins, Inc.

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