A novel role for viral-defective interfering particles in enhancing dendritic cell maturation.
Dendritic cell (DC) maturation is a crucial event in the development of adaptive immune responses that confer long-lasting protection against reinfection with the same virus. Sendai virus strain Cantell has a particularly strong ability to mature DCs independently of type I IFNs and TLR signaling, currently the best-described pathways for the induction of DC maturation. In this study, we demonstrate that defective-interfering (DI) particles present in Sendai virus-Cantell stocks are required for its robust DC maturation ability. DI particles contain incomplete genomes that are unable to replicate unless the viral polymerase is supplied by coinfection with complete virus. Accordingly, the improvement in the virus-induced maturation of DCs provided by DI particles requires standard virus coinfection and likely results from increased production of dsRNA replication intermediaries. This unique ability of DI particles to stimulate DC maturation cannot be mimicked by simply increasing the dose of standard virus. Furthermore, viruses with weak DC maturation abilities can be converted into potent DC stimulators with the addition of DI particles, supporting a potential application for DI particles as a novel natural adjuvant for viral immunizations.
Yount
Jacob S
JS
Department of Microbiology, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029, USA.
Kraus
Thomas A
TA
Horvath
Curt M
CM
Moran
Thomas M
TM
López
Carolina B
CB
D016475:3T3 Cells; D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation / Q000276:immunology; D003673:Defective Viruses / Q000276:immunology*; D003713:Dendritic Cells / Q000166:cytology* / Q000821:virology*; D005434:Flow Cytometry; D007372:Interferons / Q000378:metabolism; D051379:Mice; D020133:Reverse Transcriptase Polymerase Chain Reaction; D029082:Sendai virus / Q000276:immunology
D007372:Interferons