Tumor necrosis factor receptor-1-induced neuronal death by TRADD contributes to the pathogenesis of Japanese encephalitis

Vivek Swarup, Sulagna Das, Soumya Ghosh, Anirban Basu

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

While a number of studies have documented the neurotropism of Japanese encephalitis virus (JEV), little is known regarding the molecular mechanism of neuronal death following viral infection. The tumor necrosis factor receptor (TNFR)-associated death domain (TRADD) has been suggested to be the crucial signal adaptor that mediates all intracellular responses from TNFR-1. Using mouse (Neuro2a) and human (SK-N-SH) neuroblastoma cell lines, we have shown that the altered expression of TNFR-1 and TRADD following JEV infection regulates the downstream apoptotic cascades. Activation of TRADD led to mitochondria-mediated neuronal apoptosis. As TRADD-knockout animals or deficient cell lines are unavailable, it has been difficult to definitively address the physiological role of TRADD in diseases pathology following JEV infection. We circumvented this problem by silencing TRADD expression with small-interfering RNA (siRNA) and have found that TRADD is required for TNFR-1-initiated neuronal apoptosis following in vitro infection with JEV. Interestingly, siRNA against TRADD also decreased the viral load in Neuro2a cells. Furthermore, siRNA against TRADD increased the survival of JEV-infected mice by altering the expression of pro apoptotic versus antiapoptotic molecules. These studies show that the engagement of TNFR-1 and TRADD following JEV infection plays a crucial role in neuronal apoptosis.

Original languageEnglish (US)
Pages (from-to)771-783
Number of pages13
JournalJournal of Neurochemistry
Volume103
Issue number2
DOIs
StatePublished - Oct 1 2007
Externally publishedYes

Fingerprint

Japanese Encephalitis
Tumor Necrosis Factor Receptors
Japanese Encephalitis Virus
Viruses
Small Interfering RNA
Apoptosis
Cells
Infection
Mitochondria
Pathology
Death Domain
Animals
Cell Line
Chemical activation
Virus Diseases
Molecules
Viral Load
Neuroblastoma

Keywords

  • Apoptosis
  • Caspase 3
  • Mitochondria
  • Neuron
  • Tumor necrosis factor receptor 1
  • Tumor necrosis factor receptor-associated death domain
  • Virus

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Tumor necrosis factor receptor-1-induced neuronal death by TRADD contributes to the pathogenesis of Japanese encephalitis. / Swarup, Vivek; Das, Sulagna; Ghosh, Soumya; Basu, Anirban.

In: Journal of Neurochemistry, Vol. 103, No. 2, 01.10.2007, p. 771-783.

Research output: Contribution to journalArticle

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