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    Proc Natl Acad Sci U S A. 2005 Jun 21;102(25):8996-9001. Epub 2005 Jun 14.

    The cysteine-rich region of respiratory syncytial virus attachment protein inhibits innate immunity elicited by the virus and endotoxin.

    Polack FP, Irusta PM, Hoffman SJ, Schiatti MP, Melendi GA, Delgado MF, Laham FR, Thumar B, Hendry RM, Melero JA, Karron RA, Collins PL, Kleeberger SR.

    Department of Pediatrics, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA. fpolack@jhsph.edu

    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.

    PMID: 15956195 [PubMed - indexed for MEDLINE]

    PMCID: PMC1157014

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