Differential apoptotic signaling in primary glial cells infected with herpes simplex virus 1

Rajagopal N. Aravalli, Shuxian Hu, Timothy N. Rowen, Genya Gekker, James R. Lokensgard

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

Microglial cells and astrocytes are glial cell types that perform distinct functions and generate innate immune responses to counter invading pathogens. Herpes simplex virus 1 (HSV-1) is a neurotropic virus that is capable of causing severe, necrotizing encephalitis. HSV-1 infects both of these glial cell types. Microglial cells undergo an abortive infection, yet respond to viral infection by inducing a burst of proinflammatory cytokine and chemokine production. Following this cytokine burst, they rapidly succumb to cell death. In contrast, astrocytes do permit productive viral replication, but do not generate these same innate immune mediators. Although apoptosis has been implicated in a number of acute and chronic neurological disorders, little is known about apoptosis during viral encephalitis. In the present study, the authors investigated the effect of HSV-1 infection on cell survival and studied the mechanisms of cell-death in virus-infected, primary murine glial cells. The authors report that although apoptosis occurred rapidly in microglia, it was delayed during productive infection of astrocytes. Furthermore, microarray studies revealed significant variations in the expression of apoptotic genes between these two types of glial cells, indicating crucial differences in signaling pathways. Intrinsic as well as extrinsic pathways of apoptosis were found to be activated in both glial cell types. Specifically, genes involved in the tumor necrosis factor (TNF) signaling pathway were predominantly up-regulated in microglia, whereas genes of the Fas pathway were induced during HSV infection of astrocytes.

Original languageEnglish (US)
Pages (from-to)501-510
Number of pages10
JournalJournal of neurovirology
Volume12
Issue number6
DOIs
StatePublished - Dec 2006

Keywords

  • Apoptosis
  • Astrocytes
  • Herpes simplex virus
  • Microglia

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