Journal
JOURNAL OF IMMUNOLOGY
Volume 177, Issue 7, Pages 4503-4513Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.177.7.4503
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Funding
- NCI NIH HHS [1R24 CA 095823-01] Funding Source: Medline
- NIAID NIH HHS [U19 AI 062623-01, AI 48722, 1R01 AI 41111] Funding Source: Medline
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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.
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