Respiratory Syncytial Virus Induces TLR3 Protein and Protein Kinase R, Leading to Increased Double-Stranded RNA Responsiveness in Airway Epithelial Cells

Abstract

Respiratory syncytial virus (RSV) preferentially infects airway epithelial cells, causing bronchiolitis, upper respiratory infections, asthma exacerbations, chronic obstructive pulmonary disease exacerbations, and pneumonia in immunocompromised hosts. A replication intermediate of RSV is dsRNA. This is an important ligand for both the innate immune receptor, TLR3, and protein kinase R (PKR). One known effect of RSV infection is the increased responsiveness of airway epithelial cells to subsequent bacterial ligands (i.e., LPS). In this study, we examined a possible role for RSV infection in increasing amounts and responsiveness of another TLR, TLR3. These studies demonstrate that RSV infection of A549 and human tracheobronchial epithelial cells increases the amounts of TLR3 and PKR in a time-dependent manner. This leads to increased NF-kappaB activity and production of the inflammatory cytokine IL-8 following a later exposure to dsRNA. Importantly, TLR3 was not detected on the cell surface at baseline but was detected on the cell surface after RSV infection. The data demonstrate that RSV, via an effect on TLR3 and PKR, sensitizes airway epithelial cells to subsequent dsRNA exposure. These findings are consistent with the hypothesis that RSV infection sensitizes the airway epithelium to subsequent viral and bacterial exposures by up-regulating TLRs and increasing their membrane localization.

Genomic organization and expression analysis of Toll-like receptor 3 in grass carp (Ctenopharyngodon idella)

“…However, the exact role of TLR3 in viral infection remains controversial [6,7]. Several reports show that TLR3 contributes to the elimination of specific viruses [8,9], but others demonstrate that some viruses can benefit from TLR3 stimulation [10,11].…”

Pneumonia virus of mice: severe respiratory infection in a natural host

“…Taken together, these results suggest that TLR4 actually does not have a crucial, indispensable function in promoting host defense against a natural respiratory virus infection. However, other pattern recognition receptors (e.g., TLR3 [36], TLR7 [37]) have been explored vis à vis their role in promoting host defense against respiratory syncytial virus challenge, and might be intriguing subjects for future study with the natural PVM pathogen model.…”

Changes in the Cytokine and Toll-Like Receptor Gene Expression Following Infection of Indigenous and Commercial Chickens With Infectious bursal disease virus

“…In our study, the expression of TLR3 was up regulated significantly in indigenous chickens implying possible roles of TLR3 in dsRNA-initiated antiviral responses in IBDV-infected spleen cells. The altered expression of TLR3 has been linked to increased responsiveness to viral infection, which was reported in a number of viruses, such as respiratory syncytial virus [4], vaccinia virus [6] and hepatitis C virus (HCV) [12]. Up regulation of TLR3 has also been described for respiratory viruses such as Rhino virus, Influenza virus, and Sendai virus [1,5,7].…”