The cysteine-rich region of respiratory syncytial virus attachment protein inhibits innate immunity elicited by the virus and endotoxin.
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.
Polack
Fernando P
FP
Department of Pediatrics, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA. fpolack@jhsph.edu
Irusta
Pablo M
PM
Hoffman
Scott J
SJ
Schiatti
M Paula
MP
Melendi
Guillermina A
GA
Delgado
M Florencia
MF
Laham
Federico R
FR
Thumar
Bhagvanji
B
Hendry
R Michael
RM
Melero
Jose A
JA
Karron
Ruth A
RA
Collins
Peter L
PL
Kleeberger
Steven R
SR
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*
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