Genomewide Association Analysis of Respiratory Syncytial Virus Infection in Mice

Department of Pediatrics, University of Texas Health Science Center, Houston, Texas, USA.
Journal of Virology (Impact Factor: 4.44). 12/2009; 84(5):2257-69. DOI: 10.1128/JVI.00584-09
Source: PubMed


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.

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