Differential role for TLR3 in respiratory syncytial virus-induced chemokine expression

Brian D. Rudd, Ezra Burstein, Colin S. Duckett, Xiaoxia Li, Nicholas W. Lukacs

Research output: Contribution to journalArticle

205 Citations (Scopus)

Abstract

Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infection in young infants worldwide. Previous studies have reported that the induction of interleukin-8/CXCL8 and RANTES/CCL5 correlates with disease severity in humans. The production of these chemokines is elicited by viral replication and is NF-κB dependent. RSV, a negative-sense single-stranded RNA virus, requires full-length positive-sense RNA for synthesis of new viral RNA. The aim of our studies was to investigate whether active viral replication by RSV could evoke chemokine production through TLR3-mediated signaling pathways. In TLR3-transfected HEK 293 cells, live RSV preferentially activated chemokines in both a time- and dose-dependent manner compared to vector controls. RSV was also shown to regulate TLR3 in human lung fibroblasts and epithelial cells (MRC-5 and A549). Targeting the expression of TLR3 with small interfering RNA decreased synthesis of IP-10/CXCL10 and CCL5 but did not significantly reduce levels of CXCL8. Blocking the expression of the adapter protein MyD88 established a role for MyD88 in CXCL8 production, whereas CCL5 synthesis was found to be MyD88 independent. Production of CCL5 by RSV was induced directly through TLR3 signaling pathways and did not require interferon (IFN) signaling through the IFN-α/β receptor. TLR3 did not affect viral replication, since equivalent viral loads were recovered from RSV-infected cells despite altered TLR3 expression. Taken together, our studies indicate that TLR3 mediates inflammatory cytokine and chemokine production in RSV-infected epithelial cells.

Original languageEnglish (US)
Pages (from-to)3350-3357
Number of pages8
JournalJournal of Virology
Volume79
Issue number6
DOIs
StatePublished - Mar 2005

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Respiratory Syncytial Viruses
chemokines
Chemokines
viruses
virus replication
interferons
synthesis
negative sense, single-stranded RNA viruses
epithelial cells
Epithelial Cells
Myeloid Differentiation Factor 88
Interferon Receptors
RNA
Chemokine CCL5
vector control
HEK293 Cells
RNA Viruses
interleukin-8
Viral RNA
small interfering RNA

ASJC Scopus subject areas

  • Immunology

Cite this

Differential role for TLR3 in respiratory syncytial virus-induced chemokine expression. / Rudd, Brian D.; Burstein, Ezra; Duckett, Colin S.; Li, Xiaoxia; Lukacs, Nicholas W.

In: Journal of Virology, Vol. 79, No. 6, 03.2005, p. 3350-3357.

Research output: Contribution to journalArticle

Rudd, Brian D. ; Burstein, Ezra ; Duckett, Colin S. ; Li, Xiaoxia ; Lukacs, Nicholas W. / Differential role for TLR3 in respiratory syncytial virus-induced chemokine expression. In: Journal of Virology. 2005 ; Vol. 79, No. 6. pp. 3350-3357.
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