Virus infection induces neuronal apoptosis: A comparison with trophic factor withdrawal

T E Allsopp, M F Scallan, A Williams, J K Fazakerley

Research output: Contribution to journalArticlepeer-review


Multicellular organisms can employ a number of defences to combat viral replication, the most dramatic being implementation of a cell autonomous apoptotic process. The overall cost to the viability of an organism of losing infected cells by apoptosis may be small if the dying cells can be substituted. In contrast, suicide of irreplaceable cells such as highly specialised neurons may have a more dramatic, even fatal consequence. Previous in vitro approaches to understanding whether neurotropic viruses cause neurons to apoptose have utilised transformed cell lines. These are not in the appropriate state of differentiation to provide an accurate indication of events in vivo. We have chosen to characterise the ability of a model CNS disease-causing virus, Semliki Forest virus (SFV), to infect and trigger apoptosis in primary cultures of nerve growth factor (NGF)-dependent sensory neurons. These cells are known to die when deprived of NGF and constitute a useful indicator of apoptosis. We observe that infection causes cell death which bears the morphological hallmarks of apoptosis, this occurs even in the present of survival promoting NGF and is concomitant with new virus production. Using the TUNEL (transferase dUTP nick end labelling) technique we show that SFV-induced apoptosis involves DNA fragmentation and requires caspase (CED-3/ICE cysteine protease) activation, as does apoptosis induced by NGF-deprivation. Extensive areas of apoptosis, as defined using a combination of ultrastructural analysis and TUNEL occur in infected neonatal mouse brains. The novel evidence that infection of primary neurons with SFV induces apoptosis with activation of one or more caspases defines a system for the further anlaysis of apoptosis regulation in physiologically relevant neurons.
Original languageEnglish
Pages (from-to)50-9
Number of pages10
JournalCell Death and Differentiation
Issue number1
Publication statusPublished - Jan 1998


  • Alphavirus Infections
  • Amino Acid Chloromethyl Ketones
  • Animals
  • Apoptosis
  • Brain
  • Caspase Inhibitors
  • Caspases
  • Cell Nucleus
  • Cysteine Proteinase Inhibitors
  • DNA Fragmentation
  • Encephalitis, Viral
  • Female
  • In Situ Nick-End Labeling
  • Mice
  • Microscopy, Electron
  • Nerve Growth Factors
  • Neurons
  • Oligopeptides
  • Pregnancy
  • Semliki forest virus
  • Serine Proteinase Inhibitors
  • Tosyllysine Chloromethyl Ketone

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