Tumor necrosis factor alpha and macrophages in the brain of herpes simplex virus type 1-infected BALB/c mice

Mark Fields, Mei Zheng, Ming Zhang, Sally S. Atherton

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6 Scopus citations


After uniocular anterior chamber (AC) inoculation of herpes simplex virus type 1 (HSV-1), virus and TNF alpha (TNF-α) are detected in the suprachiasmatic nuclei (SCN). The goal of this study was to investigate the role of TNF-α and macrophages in the brain of HSV-1-infected BALB/c mice. Mice were treated with thalidomide for TNF-α inhibition or injected with clodronate liposomes to deplete macrophages, and the AC of one eye (ipsilateral) was injected with HSV-1 (KOS). The location of HSV-1, macrophages, and TNF-α was determined by fluorescence immunohistochemistry and the titer of virus was determined by plaque assay. Inhibition of TNF-α was determined by reverse transcriptase-polymerase chain reaction (RT-PCR) and depletion of macrophages was assessed by flow cytometry. In thalidomide-treated mice, TNF-α RNA levels were reduced in the SCN. Both SCN were infected by day 5 post inoculation (p.i.) and the titer of virus in the SCN contralateral to the side of injection was increased. The number of splenic macrophages was significantly reduced in clodronate-treated mice compared with controls. In macrophage-depleted mice, both SCN were infected at day 6 p.i. and the titer of virus in the SCN of these mice was increased at days 6 and 7 p.i. compared with controls. The titer of virus in the contralateral (uninoculated) eye of macrophage-depleted mice was increased at day 7 p.i. Fewer F4/80+ cells were observed in the SCN of macrophage-depleted mice. The results of these studies suggest that TNF-α plays a role in limiting virus replication in the SCN of euthymic BALB/c mice and that one source of TNF-α is macrophages.

Original languageEnglish (US)
Pages (from-to)443-455
Number of pages13
JournalJournal of NeuroVirology
Issue number6
Publication statusPublished - Dec 1 2006



  • Cytokine
  • Eye
  • Herpesvirus
  • Immunomodulator
  • Suprachiasmatic nucleus

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience
  • Virology

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