Spatiotemporal responses of astrocytes, ramified microglia, and brain macrophages to central neuronal infection with pseudorabies virus

L. Rinaman, J. P. Card, L. W. Enquist

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159 Scopus citations

Abstract

We examined the responses of astrocytes, ramified microglia, and brain macrophages to CNS neuronal infection with virulent or attenuated strains of a swine alpha herpesvirus (pseudorabies virus, PRV). After PRV inoculation of the rat stomach or pancreas, the temporal course of viral replication and induced pathology of infected neurons were assessed in the dorsal motor nucleus of the vagus (DMV) and amygdala using an antiserum generated against PRV. Specific monoclonal antibodies against glial fibrillary acidic protein (GFAP), OX42, and ED1 and morphological criteria were used to classify non- neuronal cells. Both PRV strains infected DMV and motor neurons and then passed transneuronally to infect brainstem neurons that innervate the DMV. However, the onset of neuronal infection produced by the attenuated strain occurred approximately 20 hr later than infection with the virulent strain. Animals infected with the attenuated strain also survived longer, permitting transneuronal passage of virus into forebrain areas of the visceral neuraxis. Neuronal infection with both PRV strains produced consistent alterations in astrocytes, ramified microglia, and brain macrophages that correlated spatially and temporally with progressive stages of viral replication and neuronal pathology. Early stages of infection were characterized by increases in immunoreactivity for astrocytic GFAP and microglial OX42 that preceded overt signs of neuronal pathology. At later stages, GFAP immunoreactivity decreased dramatically in focal areas of neuronal infection while OX42 immunoreactivity continued to increase. Subsequently, ED1-immunoreactive brain macrophages infiltrated these infected areas. Double immunocytochemical labeling demonstrated that some astrocytes and brain macrophages were immunopositive for viral antigens but ramified microglia were not. The responses of glia and brain macrophages are consistent with a proposed role in restricting extracellular spread of virus by isolating or phagocytosing infected cells. These phenomena may contribute to the specific transneuronal transport exhibited by PRV.

Original languageEnglish (US)
Pages (from-to)685-702
Number of pages18
JournalJournal of Neuroscience
Volume13
Issue number2
DOIs
StatePublished - 1993
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Keywords

  • Herpesvirus
  • amygdala
  • dorsal motor vagus
  • glia
  • immunohistochemistry
  • macrophages

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