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

Fernando P. Polack, Pablo M. Irusta, Scott J. Hoffman, M. Paula Schiatti, Guillermina A. Melendi, M. Florencia Delgado, Federico R. Laham, Bhagvanji Thumar, R. Michael Hendry, Jose A. Melero, Ruth A. Karron, Peter L. Collins, Steven R. Kleeberger

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)8996-9001
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number25
DOIs
StatePublished - Jun 21 2005

Keywords

  • Glycoprotein
  • Innate immunity
  • Toll-like receptor 4

ASJC Scopus subject areas

  • General

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