| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Institute for Antiviral Research, Utah State University, Logan, Utah 84341;
Vanderbilt University Medical Center, Nashville, TN 37232;
Centre d’Immunologie de Marseille-Luminy, Centre National de la Recherche Scientifique-Institut National de la Santé et de la Recherche Médicale, Marseille, France; and
Section of Immunobiology and Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06510
In the wake of RNA virus infections, dsRNA intermediates are often generated. These viral pathogen-associated molecular patterns can be sensed by a growing number of host cell cytosolic proteins and TLR3, which contribute to the induction of antiviral defenses. Recent evidence indicates that melanoma differentiation-associated gene-5 is the prominent host component mediating IFN production after exposure to the dsRNA analog, poly(I:C). We have previously reported that Punta Toro virus (PTV) infection in mice is exquisitely sensitive to treatment with poly(I:C12U), a dsRNA analog that has a superior safety profile while maintaining the beneficial activity of the parental poly(I:C) in the induction of innate immune responses. The precise host factor(s) mediating protective immunity following its administration remain to be elucidated. To assess the role of TLR3 in this process, mice lacking the receptor were used to investigate the induction of protective immunity, type I IFNs, and IL-6 following treatment. Unlike wild-type mice, those lacking TLR3 were not protected against PTV infection following poly(I:C12U) therapy and failed to produce IFN-
, IFN-
, and IL-6. In contrast, poly(I:C) treatment significantly protected TLR3–/– mice from lethal challenge despite some deficiencies in cytokine induction. There was no indication that the lack of protection was due to the fact that TLR3-deficient mice had a reduced capacity to fight infection because they were not found to be more susceptible to PTV. We conclude that TLR3 is essential to the induction of antiviral activity elicited by poly(I:C12U), which does not appear to be recognized by the cytosolic sensor of poly(I:C), melanoma differentiation-associated gene-5.
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 Grant N01-AI-15435 from the Virology Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health.
2 Address correspondence and reprint requests to Dr. Brian B. Gowen, Institute for Antiviral Research, Utah State University, 5600 Old Main, Logan, UT 84322. E-mail address: bgowen{at}cc.usu.edu
3 Abbreviations used in this paper: PTV, Punta Toro virus; ALT, alanine aminotransferase; CLDC, cationic liposome-DNA complex; mda-5, melanoma differentiation-associated gene-5; rEA, recombinant Eimeria protozoan Ag; RIG-I, retinoic acid-induced protein-I; TRIF, Toll/IL-1R domain-containing adaptor; CCID50, 50% cell culture infectious dose.
This article has been cited by other articles:
|
|
 |
|
  C. Trumpfheller, M. Caskey, G. Nchinda, M. P. Longhi, O. Mizenina, Y. Huang, S. J. Schlesinger, M. Colonna, and R. M. Steinman The microbial mimic poly IC induces durable and protective CD4+ T cell immunity together with a dendritic cell targeted vaccine PNAS, February 19, 2008; 105(7): 2574 - 2579. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Vercammen, J. Staal, and R. Beyaert Sensing of Viral Infection and Activation of Innate Immunity by Toll-Like Receptor 3 Clin. Microbiol. Rev., January 1, 2008; 21(1): 13 - 25. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
