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An In vitro Model to Study Immune Responses of Human Peripheral Blood Mononuclear Cells to Human Respiratory Syncytial Virus Infection
Published on: December 10, 2013
Association between common Toll-like receptor 4 mutations and severe respiratory syncytial virus disease
Guy Tal1, Avigdor Mandelberg, Ilan Dalal
1Pediatric Pulmonary Unit, Edith Wolfson Medical Center, Tel-Aviv University, Holon, Israel.
Insights
Genetic variations in Toll-like receptor 4 (TLR4) are linked to severe respiratory syncytial virus (RSV) bronchiolitis in infants. CD14 gene variations did not show a significant association with disease severity.
Area of Science:
- Immunogenetics
- Viral Pathogenesis
- Pediatric Infectious Diseases
Background:
- Respiratory syncytial virus (RSV) bronchiolitis severity varies greatly in infants, suggesting genetic factors influence outcomes.
- Toll-like receptor 4 (TLR4) and CD14 are key components of the innate immune system's response to RSV.
Purpose of the Study:
- To investigate the association between specific Toll-like receptor 4 (TLR4) mutations (Asp299Gly, Thr399Ile) and CD14/-159 polymorphism with the severity of RSV bronchiolitis in infants.
Main Methods:
- Genotyping of TLR4 mutations and CD14/-159 polymorphism using reverse-transcriptase polymerase chain reaction and restriction fragment-length polymorphism analysis.
- Comparison of genetic data from 99 infants with severe RSV bronchiolitis against 82 infants with mild RSV bronchiolitis and 90 healthy adults.
Main Results:
- The TLR4 Asp299Gly and Thr399Ile mutations were significantly more prevalent in infants with severe RSV bronchiolitis compared to those with mild disease or healthy adults.
- No significant association was found between the CD14/-159 polymorphism and the severity of RSV bronchiolitis.
Conclusions:
- TLR4 mutations are associated with an increased risk of severe RSV bronchiolitis in previously healthy infants.
- The CD14/-159 polymorphism does not appear to be a significant risk factor for severe RSV bronchiolitis.
Background:
The clinical spectrum of respiratory syncytial virus (RSV) bronchiolitis in previously healthy infants is extremely variable. Thus, it is likely that factors such as genetic heterogeneity contribute to disease severity. Toll-like receptor 4 (TLR4) and CD14 are part of a receptor complex involved in the innate immune response to RSV.
Methods:
The association of the TLR4 mutations (Asp299Gly and Thr399Ile) and the CD14/-159 polymorphism were analyzed in 99 infants hospitalized with severe RSV bronchiolitis (group I). Eighty-two ambulatory infants with mild RSV bronchiolitis (group II) and 90 healthy adults (group III) composed the 2 control groups. The TLR4 mutations and the CD14/-159 polymorphism were genotyped by use of reverse-transcriptase polymerase chain reaction and restriction fragment-length polymorphism analysis, respectively.
Results:
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. No association between the CD14/-159 polymorphism and RSV bronchiolitis was found.
Conclusions:
These findings suggest that TLR4 mutations, but not the CD14/-159 polymorphism, are associated with an increased risk of severe RSV bronchiolitis in previously healthy infants.
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