Brain cell type specificity and gliosis-induced activation of the human cytomegalovirus immediate-early promoter in transgenic mice

Jean Marc Fritschy, Sebastian Brandner, Adriano Aguzzi, Marieke Koedood, Bernhard Luscher, Pamela J. Mitchell

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Abstract

Human cytomegalovirus (HCMV) can cause debilitating, sometimes fatal, opportunistic infections in congenitally infected infants and in immunodeficient individuals such as patients with the acquired immunodeficiency syndrome (AIDS). Molecular mechanisms that determine cell type specificity of HCMV infection and latency are poorly understood. We recently described a transgenic mouse model for analysis of HCMV major immediate-early (IE) promoter regulation and showed that sites of IE promoter activity during murine embryogenesis correlate with known target tissues of congenital HCMV infection in human fetuses (Koedood et al., 1995). Among various permissive human tissues, the brain is a site where HCMV infections can be devastating. Here, we have used immunohistochemical double-labeling analysis to identify specific cell types with HCMV-IE promoter activity in brains of transgenic mice at several postnatal stages. IE promoter activity was restricted to some endothelial cells, ependymal cells, choroid plexus epithelia, and neurons at discrete locations in the forebrain, brainstem, and cerebellum. Endothelial cells and neurons with activity were proportionately more abundant in neonatal than in adult brains. Although the IE promoter was normally silent in most astrocytes, activity was strongly induced in reactive astrocytes in response to a neocortical stab lesion. The findings support a model, consistent with clinical literature on HCMV encephalitis, whereby tissue damage and gliosis caused by HCMV infection of endothelial and ependymal cells progressively renders adjacent permissive neurons and reactive astrocytes accessible to infection. This transgenic model system should facilitate identification of factors that regulate the HCMV IE promoter with regard to infection permissivity and reactivation from latency.

Original languageEnglish (US)
Pages (from-to)2275-2282
Number of pages8
JournalJournal of Neuroscience
Volume16
Issue number7
StatePublished - Apr 1 1996

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Gliosis
Cytomegalovirus
Transgenic Mice
Brain
Cytomegalovirus Infections
Astrocytes
Endothelial Cells
Neurons
Choroid Plexus
Opportunistic Infections
Encephalitis
Prosencephalon
Infection
Cerebellum
Brain Stem
Embryonic Development
Acquired Immunodeficiency Syndrome
Fetus
Epithelium

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Cite this

Fritschy, Jean Marc ; Brandner, Sebastian ; Aguzzi, Adriano ; Koedood, Marieke ; Luscher, Bernhard ; Mitchell, Pamela J. / Brain cell type specificity and gliosis-induced activation of the human cytomegalovirus immediate-early promoter in transgenic mice. In: Journal of Neuroscience. 1996 ; Vol. 16, No. 7. pp. 2275-2282.
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Brain cell type specificity and gliosis-induced activation of the human cytomegalovirus immediate-early promoter in transgenic mice. / Fritschy, Jean Marc; Brandner, Sebastian; Aguzzi, Adriano; Koedood, Marieke; Luscher, Bernhard; Mitchell, Pamela J.

In: Journal of Neuroscience, Vol. 16, No. 7, 01.04.1996, p. 2275-2282.

Research output: Contribution to journalArticle

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AU - Fritschy, Jean Marc

AU - Brandner, Sebastian

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