title: A chimeric A2 strain of respiratory syncytial virus (RSV) with the fusion protein of RSV strain line 19 exhibits enhanced viral load, mucus, and airway dysfunction.
abstract: Respiratory syncytial virus (RSV) is the leading cause of respiratory failure and viral death in infants. Abundant airway mucus contributes to airway obstruction in RSV disease. Interleukin-13 (IL-13) is a mediator of pulmonary mucus secretion. It has been shown that infection of BALB/c mice with the RSV line 19 strain but not with the RSV A2 laboratory strain results in lung IL-13 and mucus expression. Here, we sequenced the RSV line 19 genome and compared it to the commonly used A2 and Long strains. There were six amino acid differences between the line 19 strain and both the A2 and Long RSV strains, five of which are in the fusion (F) protein. The Long strain, like the A2 strain, did not induce lung IL-13 and mucus expression in BALB/c mice. We hypothesized that the F protein of RSV line 19 is more mucogenic than the F proteins of A2 and Long. We generated recombinant, F-chimeric RSVs by replacing the F gene of A2 with the F gene of either line 19 or Long. Infection of BALB/c mice with RSV rA2 line 19F resulted in lower alpha interferon lung levels 24 h postinfection, higher lung viral load, higher lung IL-13 levels, greater airway mucin expression levels, and greater airway hyperresponsiveness than infection with rA2-A2F or rA2-LongF. We identified the F protein of RSV line 19 as a factor that plays a role in pulmonary mucin expression in the setting of RSV infection.
authors.affiliation: Department of Pediatrics, Vanderbilt University School of Medicine, Nashville,Tennessee 37232, USA. martin.moore@emory.edu
authors.forename: Martin L
authors.initials: ML
authors.lastname: Moore
authors.forename: Michael H
authors.initials: MH
authors.lastname: Chi
authors.forename: Cindy
authors.initials: C
authors.lastname: Luongo
authors.forename: Nicholas W
authors.initials: NW
authors.lastname: Lukacs
authors.forename: Vasiliy V
authors.initials: VV
authors.lastname: Polosukhin
authors.forename: Matthew M
authors.initials: MM
authors.lastname: Huckabee
authors.forename: Dawn C
authors.initials: DC
authors.lastname: Newcomb
authors.forename: Ursula J
authors.initials: UJ
authors.lastname: Buchholz
authors.forename: James E
authors.initials: JE
authors.lastname: Crowe
authors.forename: Kasia
authors.initials: K
authors.lastname: Goleniewska
authors.forename: John V
authors.initials: JV
authors.lastname: Williams
authors.forename: Peter L
authors.initials: PL
authors.lastname: Collins
authors.forename: R Stokes
authors.initials: RS
authors.lastname: Peebles
mesh_terms: D000818:Animals; D001483:Base Sequence; D045744:Cell Line, Tumor; D016679:Genome, Viral / Q000235:genetics; D006801:Humans; D018793:Interleukin-13 / Q000096:biosynthesis / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009093:Mucus / Q000276:immunology / Q000821:virology*; D009154:Mutation / Q000235:genetics; D012313:RNA / Q000235:genetics*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism*; D018357:Respiratory Syncytial Virus Infections / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology* / Q000821:virology*; D012136:Respiratory Syncytial Viruses / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D019562:Viral Load
chemical_list: D018793:Interleukin-13; C039919:RNA, recombinant; D011993:Recombinant Fusion Proteins; D012313:RNA