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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
Cord blood gene expression in infants hospitalized with respiratory syncytial virus bronchiolitis
Hans-Olav Fjaerli1, Geir Bukholm, Camilla Skjaeret
1Faculty Division, Department of Pediatrics, Akershus University Hospital, University of Oslo, Oslo, Norway. h.o.fjarli@medisin.uio.no
Insights
Respiratory Syncytial Virus (RSV) bronchiolitis in infants is linked to down-regulated genes FAM102A, TNFRSF25, and STMN3. A pathway regulating the actin cytoskeleton is also significantly reduced in affected infants.
Area of Science:
- Immunology
- Pediatrics
- Genomics
Background:
- Respiratory Syncytial Virus (RSV) exposure leads to varied infant outcomes, from asymptomatic infection to acute bronchiolitis.
- Host, environmental, and viral factors likely influence disease severity in RSV infections.
Purpose of the Study:
- To identify host genetic differences in infants hospitalized with RSV bronchiolitis compared to those with asymptomatic RSV infection.
- To investigate specific gene expression patterns and pathways associated with severe RSV disease in neonates.
Main Methods:
- Microarray analysis of cord blood from 5 infants with RSV bronchiolitis and 5 controls.
- Quantitative Real-Time Polymerase Chain Reaction (QRT-PCR) validation of differentially expressed genes in 18 infants.
- Gene Set Enrichment Analysis (GSEA) to identify dysregulated molecular pathways.
Main Results:
- Microarray identified 15 significantly differentially expressed genes.
- QRT-PCR confirmed down-regulation of FAM102A, TNFRSF25, and STMN3 in most infants with bronchiolitis.
- GSEA revealed significant down-regulation of an actin cytoskeleton regulation pathway.
Conclusions:
- The genes FAM102A, TNFRSF25, and STMN3 are down-regulated in infants hospitalized with RSV bronchiolitis.
- A pathway involved in actin cytoskeleton regulation is also down-regulated in the cord blood of these infants.
- These findings suggest a potential genetic component influencing RSV bronchiolitis severity.
Background:
Only a few infants develop acute bronchiolitis when exposed to respiratory syncytial virus (RSV), and host, environmental, and viral properties are probably all of importance in determining the severity of infection.
Methods:
Microarray analysis was used to identify differentially expressed single genes and gene sets in cord blood from 5 infants hospitalized with RSV bronchiolitis versus cord blood from 5 control infants exposed to RSV without bronchiolitis during infancy. Quantitative real-time polymerase chain reaction (QRT-PCR) was performed on single genes in both the 5 infants selected for microarray analysis and 13 more infants hospitalized with the same disease. Gene set enrichment analysis (GSEA) was performed to identify differentially expressed gene sets within the microarray experiments.
Results:
Microarray analysis identified 15 single genes to be significantly differentially expressed between case and control infants. Eleven of these genes were evaluated with QRT-PCR, and the genes FAM102A, TNFRSF25, and STMN3 were down-regulated in all but 1 of the 18 infants. A pathway involved in regulation of the actin cytoskeleton was found to be clearly down-regulated when analyzed with GSEA.
Conclusions:
FAM102A, TNFRSF25, and STMN3 and a pathway involved in regulation of the actin cytoskeleton are down-regulated in cord blood from infants hospitalized with RSV bronchiolitis.
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