title: Functional Analysis of the 60-Nucleotide Duplication in the Respiratory Syncytial Virus Buenos Aires Strain Attachment Glycoprotein.
abstract: There are two subgroups of respiratory syncytial virus (RSV), A and B, and within each subgroup, isolates are further divided into clades. Several years ago, multiple subgroup B isolates which contained a duplication of 60 nucleotides in the glycoprotein (G) gene were described. These isolates were given a new clade designation of BA based on the site of isolation, Buenos Aires, Argentina. BA RSV strains have since become the predominant circulating clade of RSV B viruses. We hypothesized that the duplicated region in G serves to enhance the function of G in the virus life cycle. We generated recombinant viruses that express a consensus BA G gene or a consensus BA G gene lacking the duplication (GΔdup). We determined that the duplicated region functions during virus attachment to cells. Additionally, we showed that in vitro, the virus containing the duplication has a fitness advantage compared to the virus without the duplication. Our data demonstrate that the duplicated region in the BA strain G protein augments virus attachment and fitness.
  
  
  OBJECTIVE
  Respiratory syncytial virus (RSV) is an important pathogen for infants for which there is no vaccine. Different strains of RSV circulate from year to year, and the predominating strains change over time. Subgroup B RSV strains with a duplication in the attachment glycoprotein (G) emerged and then became the dominant B genotype. We found that a recombinant virus harboring the duplication bound more efficiently to cells and was more fit than a recombinant strain lacking the duplication. Our work advances a mechanism for an important natural RSV mutation.
authors.affiliation: Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia, USA Children's Healthcare of Atlanta, Atlanta, Georgia, USA.
authors.forename: Anne L
authors.initials: AL
authors.lastname: Hotard
authors.affiliation: Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia, USA Children's Healthcare of Atlanta, Atlanta, Georgia, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Laikhter
authors.affiliation: Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia, USA Children's Healthcare of Atlanta, Atlanta, Georgia, USA.
authors.forename: Kelsie
authors.initials: K
authors.lastname: Brooks
authors.affiliation: Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA Center for Asthma Research, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
authors.forename: Tina V
authors.initials: TV
authors.lastname: Hartert
authors.affiliation: Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia, USA Children's Healthcare of Atlanta, Atlanta, Georgia, USA martin.moore@emory.edu.
authors.forename: Martin L
authors.initials: ML
authors.lastname: Moore
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D005260:Female; D006023:Glycoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009711:Nucleotides / Q000235:genetics*; D011995:Recombination, Genetic; D012136:Respiratory Syncytial Viruses / Q000378:metabolism* / Q000472:pathogenicity; D017386:Sequence Homology, Amino Acid; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014774:Virulence
chemical_list: D006023:Glycoproteins; D009711:Nucleotides; D014764:Viral Proteins