title: Differential immune responses and pulmonary pathophysiology are induced by two different strains of respiratory syncytial virus.
abstract: In this study we performed comparisons of pulmonary responses between two different respiratory syncytial virus (RSV) antigenic subgroup A strains, A2 and Line 19. Line 19 strain induced significant dose-responsive airway hyperreactivity (AHR) in BALB/c mice at days 6 and 9 after infection, whereas the A2 strain induced no AHR at any dose. Histological examination indicated that A2 induced no goblet cell hyper/metaplasia, whereas the Line 19 induced goblet cell expansion and significant increases in gob5 and MUC5AC mRNA and protein levels in vivo. When examining cytokine responses, A2 strain induced significant interleukin (IL)-10 expression, whereas Line 19 strain induced significant IL-13 expression. When IL-13-/- mice were infected with Line 19 RSV, the AHR responses were abrogated along with gob5 gene expression. There was little difference in viral titer throughout the infection between the line 19- and A2-infected mice. However, the A2 strain grew to significantly higher titers than the Line 19 strain in HEp-2 cells in vitro. Thus, RSV Line 19-induced airway dysfunction does not correlate with viral load in vivo. These data demonstrate that different RSV strains of the same antigenic subgroup can elicit differential immune responses that impact the phenotypic expression of RSV-induced illness.
authors.affiliation: Department of Pathology, University of Michigan Medical School, 1301 Catherine St., Ann Arbor, MI 48109-0602, USA. nlukacs@umich.edu
authors.forename: Nicholas W
authors.initials: NW
authors.lastname: Lukacs
authors.forename: Martin L
authors.initials: ML
authors.lastname: Moore
authors.forename: Brian D
authors.initials: BD
authors.lastname: Rudd
authors.forename: Aaron A
authors.initials: AA
authors.lastname: Berlin
authors.forename: Robert D
authors.initials: RD
authors.lastname: Collins
authors.forename: Sandra J
authors.initials: SJ
authors.lastname: Olson
authors.forename: Samuel B
authors.initials: SB
authors.lastname: Ho
authors.forename: R Stokes
authors.initials: RS
authors.lastname: Peebles
mesh_terms: D000818:Animals; D016535:Bronchial Hyperreactivity / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology / Q000821:virology; D002460:Cell Line; D004306:Dose-Response Relationship, Immunologic; D005786:Gene Expression Regulation / Q000276:immunology; D020397:Goblet Cells / Q000276:immunology / Q000473:pathology / Q000821:virology; D006965:Hyperplasia / Q000276:immunology / Q000473:pathology / Q000503:physiopathology / Q000821:virology; D018793:Interleukin-13 / Q000172:deficiency / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D055271:Mucin 5AC; D009077:Mucins / Q000276:immunology; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D012136:Respiratory Syncytial Viruses / Q000276:immunology*; D013045:Species Specificity
chemical_list: D018793:Interleukin-13; C524679:Muc5ac protein, mouse; D055271:Mucin 5AC; D009077:Mucins