Nonstructural proteins 1 and 2 of respiratory syncytial virus suppress maturation of human dendritic cells

Shirin Munir, Cyril Le Nouen, Cindy Luongo, Ursula J. Buchholz, Peter L. Collins, Alexander Bukreyev

Research output: Contribution to journalArticle

71 Citations (Scopus)

Abstract

Human respiratory syncytial virus (RSV) is the most important agent of serious pediatric respiratory tract disease worldwide. One of the main characteristics of RSV is that it readily reinfects and causes disease throughout life without the need for significant antigenic change. The virus encodes nonstructural protein 1 (NS1) and NS2, which are known to suppress type I interferon (IFN) production and signaling. In the present study, we monitored the maturation of human monocyte-derived myeloid dendritic cells (DC) following inoculation with recombinant RSVs bearing deletions of the NS1 and/or NS2 proteins and expressing enhanced green fluorescent protein. Deletion of the NS1 protein resulted in increased expression of cell surface markers of DC maturation and an increase in the expression of multiple cytokines and chemokines. This effect was enhanced somewhat by further deletion of the NS2 protein, although deletion of NS2 alone did not have a significant effect. The upregulation was largely inhibited by pretreatment with a blocking antibody against the type IIFN receptor, suggesting that suppression of DC maturation by NS1/2 is, at least in part, a result of IFN antagonism mediated by these proteins. Therefore, this study identified another effect of the NS1 and NS2 proteins. The observed suppression of DC maturation may result in decreased antigen presentation and T-lymphocyte activation, leading to incomplete and/or weak immune responses that might contribute to RSV reinfection.

Original languageEnglish (US)
Pages (from-to)8780-8796
Number of pages17
JournalJournal of Virology
Volume82
Issue number17
DOIs
StatePublished - Sep 2008
Externally publishedYes

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Respiratory Syncytial Viruses
dendritic cells
Dendritic Cells
viruses
Proteins
proteins
interferons
Human respiratory syncytial virus
Respiratory Tract Diseases
antigen presentation
Interferon Type I
Blocking Antibodies
Antigen Presentation
Myeloid Cells
chemokines
lymphocyte proliferation
Lymphocyte Activation
green fluorescent protein
Chemokines
monocytes

ASJC Scopus subject areas

  • Immunology

Cite this

Nonstructural proteins 1 and 2 of respiratory syncytial virus suppress maturation of human dendritic cells. / Munir, Shirin; Le Nouen, Cyril; Luongo, Cindy; Buchholz, Ursula J.; Collins, Peter L.; Bukreyev, Alexander.

In: Journal of Virology, Vol. 82, No. 17, 09.2008, p. 8780-8796.

Research output: Contribution to journalArticle

Munir, Shirin ; Le Nouen, Cyril ; Luongo, Cindy ; Buchholz, Ursula J. ; Collins, Peter L. ; Bukreyev, Alexander. / Nonstructural proteins 1 and 2 of respiratory syncytial virus suppress maturation of human dendritic cells. In: Journal of Virology. 2008 ; Vol. 82, No. 17. pp. 8780-8796.
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