title: Comparison of temporal transcriptomic profiles from immature lungs of two rat strains reveals a viral response signature associated with chronic lung dysfunction.
abstract: Early life respiratory viral infections and atopic characteristics are significant risk factors for the development of childhood asthma. It is hypothesized that repeated respiratory viral infections might induce structural remodeling by interfering with the normal process of lung maturation; however, the specific molecular processes that underlie these pathological changes are not understood. To investigate the molecular basis for these changes, we used an established Sendai virus infection model in weanling rats to compare the post-infection transcriptomes of an atopic asthma susceptible strain, Brown Norway, and a non-atopic asthma resistant strain, Fischer 344. Specific to this weanling infection model and not described in adult infection models, Sendai virus in the susceptible, but not the resistant strain, results in morphological abnormalities in distal airways that persist into adulthood. Gene expression data from infected and control lungs across five time points indicated that specific features of the immune response following viral infection were heightened and prolonged in lungs from Brown Norway rats compared with Fischer 344 rats. These features included an increase in macrophage cell number and related gene expression, which then transitioned to an increase in mast cell number and related gene expression. In contrast, infected Fischer F344 lungs exhibited more efficient restoration of the airway epithelial morphology, with transient appearance of basal cell pods near distal airways. Together, these findings indicate that the pronounced macrophage and mast cell responses and abnormal re-epithelialization precede the structural defects that developed and persisted in Brown Norway, but not Fischer 344 lungs.
authors.affiliation: Laboratory of Genetics, University of Wisconsin, Madison, Wisconsin, United States of America.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Hines
authors.affiliation: School of Pharmacy, University of Wisconsin, Madison, Wisconsin, United States of America; Department of Medicine, University of Wisconsin, Madison, Wisconsin, United States of America.
authors.forename: Renee J
authors.initials: RJ
authors.lastname: Szakaly
authors.affiliation: Department of Statistics, University of Wisconsin, Madison, Wisconsin, United States of America.
authors.forename: Ning
authors.initials: N
authors.lastname: Leng
authors.affiliation: School of Pharmacy, University of Wisconsin, Madison, Wisconsin, United States of America.
authors.forename: Anais T
authors.initials: AT
authors.lastname: Webster
authors.affiliation: Laboratory of Genetics, University of Wisconsin, Madison, Wisconsin, United States of America.
authors.forename: Jamie M
authors.initials: JM
authors.lastname: Verheyden
authors.affiliation: Laboratory of Genetics, University of Wisconsin, Madison, Wisconsin, United States of America.
authors.forename: Amber J
authors.initials: AJ
authors.lastname: Lashua
authors.affiliation: Department of Statistics, University of Wisconsin, Madison, Wisconsin, United States of America.
authors.forename: Christina
authors.initials: C
authors.lastname: Kendziorski
authors.affiliation: Department of Medicine, University of Wisconsin, Madison, Wisconsin, United States of America.
authors.forename: Louis A
authors.initials: LA
authors.lastname: Rosenthal
authors.affiliation: Department of Pediatrics, University of Wisconsin, Madison, Wisconsin, United States of America.
authors.forename: James E
authors.initials: JE
authors.lastname: Gern
authors.affiliation: School of Pharmacy, University of Wisconsin, Madison, Wisconsin, United States of America.
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Sorkness
authors.affiliation: Laboratory of Genetics, University of Wisconsin, Madison, Wisconsin, United States of America.
authors.forename: Xin
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Medicine, University of Wisconsin, Madison, Wisconsin, United States of America; Department of Pediatrics, University of Wisconsin, Madison, Wisconsin, United States of America.
authors.forename: Robert F
authors.initials: RF
authors.lastname: Lemanske
mesh_terms: D000818:Animals; D001249:Asthma / Q000821:virology; D015415:Biomarkers / Q000378:metabolism; D002452:Cell Count; D020869:Gene Expression Profiling; D063990:Gene Ontology; D008168:Lung / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology / Q000821:virology*; D008264:Macrophages / Q000473:pathology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D020545:Respiratory Mucosa / Q000378:metabolism / Q000821:virology; D010253:Respirovirus Infections / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D029082:Sendai virus / Q000502:physiology*; D013045:Species Specificity; D013997:Time Factors
chemical_list: D015415:Biomarkers