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* Department of Microbiology, Mount Sinai School of Medicine, New York, NY 10029; and
Immunobiology Center, Mount Sinai School of Medicine, New York, NY 10029
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.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by Grants 1R01AI41111 and U19AI062623-01 (to T.M.M.), and AI48722 (to C.M.H.) from the National Institute of Allergy and Infectious Diseases, and by funds granted by the Charles H. Revson Foundation (to C.B.L.). The statements made and views expressed, however, are solely the responsibility of the authors. Electron microscopy was performed at the Mount Sinai School of Medicine Microscopy Shared Resource Facility supported with funding from National Institutes of Health-National Cancer Institute shared resources (1 R24 CA095823-01) and National Science Foundation major research instrumentation (DBI-9724504) grants.
2 Current address: Department of Medicine and Department of Biochemistry, Molecular Biology, and Cell Biology, Northwestern University; Department of Medicine, Evanston Northwestern, Evanston, IL 60208.
3 Address correspondence and reprint requests to Dr. Carolina B. López, Department of Microbiology, Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1124, New York, NY 10029. E-mail address: Carolina.Lopez{at}mssm.edu
4 Abbreviations used in this paper: DC, dendritic cell; SeV, Sendai virus; C, Cantell; DI, defective interfering; RIG-I, retinoic acid-inducible gene I; qRT-PCR, quantitative RT-PCR; BM-DC, bone marrow-derived DC; NP, nucleoprotein; HA, hemagglutination; MOI, multiplicity of infection; pDI, purified DI; PKR, dsRNA-dependent protein kinase; TCID, tissue culture infectious dose; I:HA, infectivity to total HA particles.
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