| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Department of Microbiology, Mount Sinai School of Medicine, New York, NY 10029; and
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110
Defective interfering (DI) particles are byproducts of virus replication that potently enhance dendritic cell (DC) maturation by virus infection. DI particles have been reported for many different viruses and are strong inducers of type I IFNs. The cellular mechanisms involved in the response to DI particles are not known. In this study, we show that 1) DI particles are recognized by more than one viral sensor independently of TLRs and type I IFN signaling; 2) The helicase MDA5 participates in the detection of DI genomes as MDA5-deficient DCs respond inefficiently to Sendai virus stocks containing DI particles; 3) DI particles stimulate the expression of IRF3-responsive genes by a uniquely potent mechanism when compared with other prototypic viral stimulus; and 4) the efficient detection of DI particles overcomes virus immune antagonism. These data highlight the outstanding adjuvant capacity of DI particles in stimulating mouse and human DCs. They also offer biological relevance to the previously reported inhibition of MDA5 by different paramyxovirus V proteins. The unique mechanism by which DI particles trigger the maturation of DCs represents a novel strategy that could be further exploited for the development of potent adjuvant molecules.
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, U19AI062623-01, and HHSN266200500021C (to T.M.M.) from the National Institute of Allergy and Infectious Diseases. L.G. is a postdoctoral fellow of the Cancer Research Institute.
2 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
3 Abbreviations used in this paper: DC, dendritic cell; SeV, Sendai virus; EMCV, Encephalomyocarditis virus; DI, defective interfering; NDV, Newcastle Disease virus; pDI, purified DI; SeV LD, SeV low DI; SeV HD, SeV high DI; qRT-PCR, quantitative RT-PCR; hpi, hours post infection; MOI, multiplicity of infection; Rig-I, retinoic acid-inducible gene 1; MDA5, melanoma differentiation-associated gene 5; hpi, hours post infection.
This article has been cited by other articles:
|
|
 |
|
  J.-P. Parisien, D. Bamming, A. Komuro, A. Ramachandran, J. J. Rodriguez, G. Barber, R. D. Wojahn, and C. M. Horvath A Shared Interface Mediates Paramyxovirus Interference with Antiviral RNA Helicases MDA5 and LGP2 J. Virol., July 15, 2009; 83(14): 7252 - 7260. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. K. Pfaller and K.-K. Conzelmann Measles Virus V Protein Is a Decoy Substrate for I{kappa}B Kinase {alpha} and Prevents Toll-Like Receptor 7/9-Mediated Interferon Induction J. Virol., December 15, 2008; 82(24): 12365 - 12373. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. K. Roth-Cross, S. J. Bender, and S. R. Weiss Murine Coronavirus Mouse Hepatitis Virus Is Recognized by MDA5 and Induces Type I Interferon in Brain Macrophages/Microglia J. Virol., October 15, 2008; 82(20): 9829 - 9838. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
