title: The cysteine-rich region of respiratory syncytial virus attachment protein inhibits innate immunity elicited by the virus and endotoxin.
abstract: The attachment protein (glycoprotein) of respiratory syncytial virus (RSV) has long been associated with disease potentiation and respiratory symptoms. The glycoprotein has a conserved cysteine-rich region (GCRR) whose function is unknown and which is not necessary for efficient viral replication. In this report, we show that the GCRR is a powerful inhibitor of the innate immune response against RSV, and that early secretion of glycoprotein is critical to modulate inflammation after RSV infection. Importantly, the GCRR is also a potent inhibitor of cytokine production mediated by several TLR agonists, indicating that this peptide sequence displays broad antiinflammatory properties. These findings have important implications for RSV pathogenesis and describe an inhibitor of TLR-mediated inflammatory responses that could have clinical applications.
authors.affiliation: Department of Pediatrics, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA. fpolack@jhsph.edu
authors.forename: Fernando P
authors.initials: FP
authors.lastname: Polack
authors.forename: Pablo M
authors.initials: PM
authors.lastname: Irusta
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Hoffman
authors.forename: M Paula
authors.initials: MP
authors.lastname: Schiatti
authors.forename: Guillermina A
authors.initials: GA
authors.lastname: Melendi
authors.forename: M Florencia
authors.initials: MF
authors.lastname: Delgado
authors.forename: Federico R
authors.initials: FR
authors.lastname: Laham
authors.forename: Bhagvanji
authors.initials: B
authors.lastname: Thumar
authors.forename: R Michael
authors.initials: RM
authors.lastname: Hendry
authors.forename: Jose A
authors.initials: JA
authors.lastname: Melero
authors.forename: Ruth A
authors.initials: RA
authors.lastname: Karron
authors.forename: Peter L
authors.initials: PL
authors.lastname: Collins
authors.forename: Steven R
authors.initials: SR
authors.lastname: Kleeberger
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D017124:Conserved Sequence; D003545:Cysteine; D005260:Female; D006021:Glycophorins / Q000032:analysis; D007113:Immunity, Innate / Q000187:drug effects*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008070:Lipopolysaccharides / Q000633:toxicity; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology; D012136:Respiratory Syncytial Viruses / Q000276:immunology / Q000502:physiology*; D014759:Viral Envelope Proteins / Q000276:immunology / Q000494:pharmacology*
chemical_list: D015703:Antigens, CD; C066028:G protein, Bovine respiratory syncytial virus; D006021:Glycophorins; D008070:Lipopolysaccharides; D016328:NF-kappa B; D010446:Peptide Fragments; D014759:Viral Envelope Proteins; C116204:attachment protein G; D003545:Cysteine