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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
Whole blood gene expression in infants with respiratory syncytial virus bronchiolitis
Hans-Olav Fjaerli1, Geir Bukholm, Anne Krog
1University of Oslo, Faculty Division Akershus University Hospital, Department of Paediatrics, Akershus University Hospital, Norway. h.o.fjarli@medisin.uio.no
Insights
Respiratory syncytial virus (RSV) bronchiolitis in infants shows distinct gene expression patterns. Interferon alpha-inducible protein 27 (IFI27) was upregulated, while Charcot-Leyden crystal protein (CLC) was downregulated in affected infants.
Area of Science:
- Immunology
- Virology
- Pediatrics
Background:
- Respiratory syncytial virus (RSV) is a leading cause of infant bronchiolitis globally.
- Disease severity is influenced by environmental, viral, and host factors.
- Understanding the host's systemic response is crucial for managing RSV infections.
Purpose of the Study:
- To investigate gene expression differences in infants with RSV bronchiolitis compared to healthy controls.
- To identify specific genes associated with the host response to RSV infection.
Main Methods:
- Microarray technology was used to measure mRNA gene expression in whole blood.
- Gene expression levels were validated using quantitative real-time polymerase chain reaction (QRT-PCR).
- Study included hospitalized infants with RSV bronchiolitis and age-matched controls.
Main Results:
- Nearly 50% of the top 30 differentially expressed genes were related to immunological processes.
- Interferon, alpha-inducible protein 27 (IFI27) showed significant upregulation.
- Charcot-Leyden crystal protein (CLC) was found to be significantly downregulated.
- QRT-PCR confirmed IFI27 upregulation and CLC downregulation in the majority of infants.
Conclusions:
- IFI27 is upregulated and CLC is downregulated in infants hospitalized with RSV bronchiolitis.
- These specific gene expression changes in response to RSV require further investigation.
- Elucidating the specificity of these gene expressions is important for understanding host response in moderate bronchiolitis.
Background:
Respiratory syncytial virus (RSV) is a major cause of viral bronchiolitis in infants worldwide, and environmental, viral and host factors are all of importance for disease susceptibility and severity. To study the systemic host response to this disease we used the microarray technology to measure mRNA gene expression levels in whole blood of five male infants hospitalised with acute RSV, subtype B, bronchiolitis versus five one year old male controls exposed to RSV during infancy without bronchiolitis. The gene expression levels were further evaluated in a new experiment using quantitative real-time polymerase chain reaction (QRT-PCR) both in the five infants selected for microarray and in 13 other infants hospitalised with the same disease.
Results:
Among the 30 genes most differentially expressed by microarray nearly 50% were involved in immunological processes. We found the highly upregulated interferon, alpha-inducible protein 27 (IFI27) and the highly downregulated gene Charcot-Leyden crystal protein (CLC) to be the two most differentially expressed genes in the microarray study. When performing QRT-PCR on these genes IFI27 was upregulated in all but one infant, and CLC was downregulated in all 18 infants, and similar to that given by microarray.
Conclusion:
The gene IFI27 is upregulated and the gene CLC is downregulated in whole blood of infants hospitalised with RSV, subtype B, bronchiolitis and is not reported before. More studies are needed to elucidate the specificity of these gene expressions in association with host response to this virus in bronchiolitis of moderate severity.
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