Nonstructural proteins 1 and 2 of respiratory syncytial virus suppress maturation of human dendritic cells.
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 I IFN 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.
Munir
Shirin
S
Laboratory of Infectious Disease, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-8007, USA.
Le Nouen
Cyril
C
Luongo
Cindy
C
Buchholz
Ursula J
UJ
Collins
Peter L
PL
Bukreyev
Alexander
A
D000328:Adult; D000818:Animals; D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D016207:Cytokines / Q000032:analysis; D003588:Cytopathogenic Effect, Viral; D053938:DNA Fragmentation; D003713:Dendritic Cells / Q000378:metabolism* / Q000821:virology; D017353:Gene Deletion; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D011995:Recombination, Genetic; D018113:Respiratory Syncytial Virus, Human / Q000235:genetics / Q000502:physiology*; D013997:Time Factors; D014709:Vero Cells; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000502:physiology*
D017304:Annexin A5; D016207:Cytokines; D017361:Viral Nonstructural Proteins; D049452:Green Fluorescent Proteins; D053148:Caspase 3