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

doi:10.1073/pnas.0409478102

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

Bloomberg School of Public Health

Research output: Contribution to journal › Article › peer-review

81 Scopus citations

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 language	English (US)
Pages (from-to)	8996-9001
Number of pages	6
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	102
Issue number	25
DOIs	https://doi.org/10.1073/pnas.0409478102
State	Published - Jun 21 2005

Keywords

Glycoprotein
Innate immunity
Toll-like receptor 4

ASJC Scopus subject areas

General

Access to Document

10.1073/pnas.0409478102

Cite this

Polack, F. P., Irusta, P. M., Hoffman, S. J., Schiatti, M. P., Melendi, G. A., Delgado, M. F., Laham, F. R., Thumar, B., Hendry, R. M., Melero, J. A., Karron, R. A., Collins, P. L., & Kleeberger, S. R. (2005). The cysteine-rich region of respiratory syncytial virus attachment protein inhibits innate immunity elicited by the virus and endotoxin. Proceedings of the National Academy of Sciences of the United States of America, 102(25), 8996-9001. https://doi.org/10.1073/pnas.0409478102

The cysteine-rich region of respiratory syncytial virus attachment protein inhibits innate immunity elicited by the virus and endotoxin. / Polack, Fernando P.; Irusta, Pablo M.; Hoffman, Scott J. et al.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 102, No. 25, 21.06.2005, p. 8996-9001.

Research output: Contribution to journal › Article › peer-review

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 2005, 'The cysteine-rich region of respiratory syncytial virus attachment protein inhibits innate immunity elicited by the virus and endotoxin', Proceedings of the National Academy of Sciences of the United States of America, vol. 102, no. 25, pp. 8996-9001. https://doi.org/10.1073/pnas.0409478102

@article{4ef949bfecdb47e7854e7d0f68590a49,

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.",

keywords = "Glycoprotein, Innate immunity, Toll-like receptor 4",

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

year = "2005",

month = jun,

day = "21",

doi = "10.1073/pnas.0409478102",

language = "English (US)",

volume = "102",

pages = "8996--9001",

journal = "Proceedings of the National Academy of Sciences of the United States of America",

issn = "0027-8424",

publisher = "National Academy of Sciences",

number = "25",

}

TY - JOUR

T1 - The cysteine-rich region of respiratory syncytial virus attachment protein inhibits innate immunity elicited by the virus and endotoxin

AU - Polack, Fernando P.

AU - Irusta, Pablo M.

AU - Hoffman, Scott J.

AU - Schiatti, M. Paula

AU - Melendi, Guillermina A.

AU - Delgado, M. Florencia

AU - Laham, Federico R.

AU - Thumar, Bhagvanji

AU - Hendry, R. Michael

AU - Melero, Jose A.

AU - Karron, Ruth A.

AU - Collins, Peter L.

AU - Kleeberger, Steven R.

PY - 2005/6/21

Y1 - 2005/6/21

N2 - 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.

AB - 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.

KW - Glycoprotein

KW - Innate immunity

KW - Toll-like receptor 4

UR - http://www.scopus.com/inward/record.url?scp=21144433989&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=21144433989&partnerID=8YFLogxK

U2 - 10.1073/pnas.0409478102

DO - 10.1073/pnas.0409478102

M3 - Article

C2 - 15956195

AN - SCOPUS:21144433989

SN - 0027-8424

VL - 102

SP - 8996

EP - 9001

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

IS - 25

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this