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Updated: Jun 17, 2026
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
Genomewide association analysis of respiratory syncytial virus infection in mice
James M Stark1, M Michael Barmada, Abby V Winterberg
1Department of Pediatrics, University of Texas Health Science Center, Houston, Texas, USA. starkj@childrensdayton.org
Insights
Individual susceptibility influences respiratory syncytial virus (RSV) severity. Genetic analysis identified a major quantitative trait locus, Rsvs1, on mouse chromosome 6, implicating the cystic fibrosis transmembrane conductance regulator (CFTR) gene in RSV infection outcomes.
Area of Science:
- Genetics
- Immunology
- Virology
Background:
- Respiratory syncytial virus (RSV) is a leading cause of infant lower respiratory tract infections, yet disease severity varies significantly among individuals.
- Previous studies identified genetic differences in RSV susceptibility between AKR/J (susceptible) and C57BL/6J (resistant) mouse strains.
- Mice lacking the cystic fibrosis transmembrane conductance regulator (CFTR) gene exhibit increased susceptibility to RSV infection.
Purpose of the Study:
- To identify genetic factors contributing to individual differences in respiratory syncytial virus (RSV) disease severity.
- To investigate the role of the cystic fibrosis transmembrane conductance regulator (CFTR) in modulating RSV infection outcomes.
Main Methods:
- Quantitative trait locus (QTL) analysis was performed on recombinant backcross and F2 progeny derived from AKR/J and C57BL/6J mice infected with RSV.
- Lung viral titers were measured to assess susceptibility.
- Microarray analysis was used to compare lung gene expression profiles between parental strains during RSV infection.
Main Results:
- A major QTL, designated Rsvs1, was identified on proximal mouse chromosome 6 in both recombinant populations.
- Candidate genes within the Rsvs1 interval, including Cftr, were identified through microarray analysis.
- These findings correlate genetic loci with differential RSV susceptibility and viral load.
Conclusions:
- The study identified a significant genetic locus (Rsvs1) on mouse chromosome 6 associated with RSV susceptibility.
- The cystic fibrosis transmembrane conductance regulator (CFTR) is strongly supported as a modifier gene influencing RSV infection severity.
- Understanding these genetic factors provides insights into RSV pathogenesis and potential therapeutic targets, particularly for infants with cystic fibrosis.
Abstract:
Respiratory syncytial virus (RSV) is the major cause of lower respiratory tract infection in infants, with about half being infected in their first year of life. Yet only 2 to 3% of infants are hospitalized for RSV infection, suggesting that individual susceptibility contributes to disease severity. Previously, we determined that AKR/J (susceptible) mice developed high lung RSV titers and showed delayed weight recovery, whereas C57BL/6J (resistant) mice demonstrated low lung RSV titers and rapid weight recovery. In addition, we have reported that gene-targeted mice lacking the cystic fibrosis transmembrane conductance regulator (Cftr; ATP-binding cassette subfamily C, member 7) are susceptible to RSV infection. For this report, recombinant backcross and F2 progeny derived from C57BL/6J and AKR/J mice were infected with RSV, their lung titers were measured, and quantitative trait locus (QTL) analysis was performed. A major QTL, designated Rsvs1, was identified on proximal mouse chromosome 6 in both recombinant populations. Microarray analysis comparing lung transcripts of the parental strains during infection identified several candidate genes that mapped to the Rsvs1 interval, including Cftr. These findings add to our understanding of individual RSV susceptibility and strongly support a modifier role for CFTR in RSV infection, a significant cause of respiratory morbidity in infants with cystic fibrosis.
