TNFR1 plays a critical role in the control of severe HSV-1 encephalitis

  • Márcia Carvalho Vilela
  • , Graciela Kunrath Lima
  • , David Henrique Rodrigues
  • , Norinne Lacerda-Queiroz
  • , Daniel Santos Mansur
  • , Aline Silva de Miranda
  • , Milene Alvarenga Rachid
  • , Erna Geessien Kroon
  • , Leda Quercia Vieira
  • , Marco Antônio Campos
  • , Mauro Martins Teixeira
  • , Antônio Lúcio Teixeira

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

Herpes simplex virus-1 (HSV-1) is a pathogen for humans that may cause severe encephalitis. Tumor necrosis factor α (TNF-α) plays a role in several viral diseases of the central nervous system (CNS). The classic proinflammatory activities of TNF-α are mediated mainly through activation of the receptor 1 for TNF-α (TNFR1). However, when HSV-1 is inoculated in the periphery, TNF-α seems to protect C57Bl/6 mice against encephalitis by a mechanism independent of TNFR1. This study aims to investigate the role of TNFR1 in HSV-1 encephalitis induced by the inoculation of the virus into the brain. Wild-type C57BL/6 (WT) and TNFR1-/- were inoculated with 102 plaque-forming units of HSV-1 by the intracranial route. Infection with HSV-1 was lethal in TNFR1-/- mice in early times after infection. TNFR1-/- mice had reduced expression of the chemokines CCL3 and CCL5, and decreased leukocyte adhesion in the brain vasculature compared to WT mice 4 days post-infection (dpi). At this time point TNFR1-/- infected mice also had higher HSV-1 viral replication and more injuries in the brain, especially in the hippocampus. In conclusion, TNFR1 seems to play a relevant role in the control of viral replication in the CNS when HSV-1 is inoculated by intracranial route.

Original languageEnglish (US)
Pages (from-to)58-62
Number of pages5
JournalNeuroscience Letters
Volume479
Issue number1
DOIs
StatePublished - Jul 2010
Externally publishedYes

Keywords

  • Herpes simplex virus type 1
  • Neuroinflammation
  • TNFR1

ASJC Scopus subject areas

  • General Neuroscience

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