Strain-specific transcriptomics suggested virus-responsive (<i>Oasl1</i>, <i>Irg1</i>, <i>Mx1</i>) and epidermal differentiation complex (<i>Krt4</i>, <i>Lce3a</i>) genes may contribute to TLR4-independent defense against RSV in resistant strains including C57BL/6J.
The results indicated that TLR4 and C23 gene knockdown decreased the amount of F protein in RSV-infected N2a cells, inhibited RSV propagation, attenuated N2a neuronal injury, diminished cell apoptosis levels, downregulated TLR3 and TLR7 protein expression, and reduced inflammatory protein expression.
The pathogenesis of respiratory syncytial virus (RSV) and influenza A virus (IAV) have been linked to TLR4 activation, and we examined the action of POPG and PI as potential antagonists of the pathology of these viruses.
Two independent populations of infants with RSV bronchiolitis revealed that the severity of RSV infection is determined by the TLR4 genotype of the individual and by environmental exposure to LPS.
The aim of this study was to investigate the possible role of polymorphisms of TLR4, Asp299Gly and Thr399Ile and CD14, C-159T and C-550T in the development of RSV bronchiolitis.
MDD exhibited significant antiviral and anti-inflammatory effects on decreasing levels of Eotaxin, IL-4 and IFN-γ in serum and lung tissue, inhibiting pneumonia, decreasing lung viral loads and reversaling RSV-induced inflammation through down-regulation of TLR4 and NF-κB mRNA expression in the lung tissue of RSV-infected mice.
Toll-like receptor 4 (TLR4), a signaling receptor for structurally diverse microbe-associated molecular patterns, is activated by the RSV fusion (F) protein and by bacterial lipopolysaccharide (LPS) in a CD14-dependent manner.
Thus, although isolated viral compounds such as purified RSV F protein may bind TLR4 and/or CD14, a direct interaction between intact RSV particles and the human TLR4 receptor complex does not seem to play a biological role in RSV pathogenesis.
By genotyping 236 children with RSV infection and 219 healthy controls we found no association between the risk of severe RSV infection and Asp299Gly polymorphisms (P>0.05), and we demonstrate that the TLR4Asp299Gly genotype does not influence susceptibility to either RSV serotype A or B (P>0.05).
Our data suggest that heterozygosity of these two extracellular TLR4 polymorphisms is highly associated with symptomatic RSV disease in high-risk infants and support a dual role for TLR4 SNPs in prematurity and increased susceptibility to RSV not revealed by analysis of either alone.
No TLR4 mutations were found.The frequencies of both the CC genotype and the C allele of CD14 -550 C/T were significantly higher in children with RSV bronchiolitis than in the control subjects.
We genotyped the CD14 promotor polymorphism -C159T and the two common TLR4 amino acid variants (D259G, and T359I) in 131 infants with severe RSV associated diseases and 270 controls.
The presence of TLR4 mutations (Asp299Gly and Thr399Ile) were associated with severe RSV bronchiolitis and were significantly over-represented in groups II and III.
Each of the TLR4 mutations, either alone or in cosegregation, were associated with severe RSV bronchiolitis: the Asp299Gly and Thr399Ile mutations were significantly overrepresented in group I, compared with groups II and III.
This theory is supported by studies showing that Toll-like receptor 4 is activated by respiratory syncytial virus (RSV), leading to production of inflammatory cytokines.
The first response occurs early after RSV inoculation, is AM and TLR4 dependent, and is viral replication independent, whereas the second response involves epithelial cells and/or inflammatory cells, is TLR4 independent, and requires viral replication.