| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Department of Pathology and Molecular Medicine and
Department of Biochemistry and Biomedical Sciences, Center for Gene Therapeutics, McMaster University, Hamilton, Ontario, Canada
The innate immune system responds to pathogen infection by eliciting a nonspecific immune response following the recognition of various pathogen-associated molecular patterns. TLRs and the RNA helicases retinoic acid-inducible gene I (RIG-I) and melanoma differentiation-associated gene 5 recognize foreign nucleic acid within endosomal and cytoplasmic compartments, respectively, initiating a signaling cascade that involves the induction of type I IFN through the transcription factors IFN regulatory factor (IRF) 3 and NF-
B. However, a recent paradigm has emerged in which bacterial DNA and double-stranded B-form DNA trigger type I IFN production through an uncharacterized TLR- and RIG-I-independent pathway. We have previously described a response in primary fibroblasts wherein the entry of diverse RNA- and DNA-enveloped virus particles is sufficient to induce a subset of IFN-stimulated genes and a complete antiviral response in an IRF3-dependent, IFN-independent manner. In this study, we show that the innate immune response to virus particle entry is independent of both TLR and RIG-I pathways, confirming the existence of novel innate immune mechanisms that result in the activation of IRF3. Furthermore, we propose a model of innate antiviral immunity in which exposure to increasing numbers of virus particles elevates the complexity of the cellular response from an intracellular, IFN-independent response to one involving secretion of cytokines and activation of infiltrating immune cells.
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 a grant from the Canadian Institutes of Health Research. K.L.M. was supported by an Rx&D Health Research Foundation Career Award.
2 Address correspondence and reprint requests to Dr. Karen L. Mossman, Department of Pathology and Molecular Medicine, Centre for Gene Therapeutics, Michael G. DeGroote Centre for Learning and Discovery Room 5026, 1200 Main St. West, Hamilton, Ontario, Canada. E-mail address: mossk{at}mcmaster.ca
3 Abbreviations used in this paper: ISG, IFN-stimulated gene; IRF, IFN regulatory factor; TBK, TANK-binding kinase; WT, wild type; SeV, Sendai virus; DC, dendritic cell; HEL, human embryonic lung; HCMV, human CMV; VSV, vesicular stomatitis virus; poly(I:C), polyinosinic/polycytidylic acid; L-Gln, L-glutamine; MEF, murine embryonic fibroblasts; MOI, multiplicity of infection; 1°, primary; RIG-I, retinoic acid-inducible gene I.
This article has been cited by other articles:
|
|
 |
|
  M. K. Choi, Z. Wang, T. Ban, H. Yanai, Y. Lu, R. Koshiba, Y. Nakaima, S. Hangai, D. Savitsky, M. Nakasato, et al. A selective contribution of the RIG-I-like receptor pathway to type I interferon responses activated by cytosolic DNA PNAS, October 20, 2009; 106(42): 17870 - 17875. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. H. Hancock, K. L. Mossman, and J. R. Smiley Cell Fusion-Induced Activation of Interferon-Stimulated Genes Is Not Required for Restriction of a Herpes Simplex Virus VP16/ICP0 Mutant in Heterokarya Formed between Permissive and Restrictive Cells J. Virol., September 1, 2009; 83(17): 8976 - 8979. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. S. Noyce, S. E. Collins, and K. L. Mossman Differential Modification of Interferon Regulatory Factor 3 following Virus Particle Entry J. Virol., May 1, 2009; 83(9): 4013 - 4022. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. K. Miyahira, A. Shahangian, S. Hwang, R. Sun, and G. Cheng TANK-Binding Kinase-1 Plays an Important Role during In Vitro and In Vivo Type I IFN Responses to DNA Virus Infections J. Immunol., February 15, 2009; 182(4): 2248 - 2257. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Verpooten, Y. Ma, S. Hou, Z. Yan, and B. He Control of TANK-binding Kinase 1-mediated Signaling by the {gamma}134.5 Protein of Herpes Simplex Virus 1 J. Biol. Chem., January 9, 2009; 284(2): 1097 - 1105. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. L. Mossman, M. F. Mian, N. M. Lauzon, C. L. Gyles, B. Lichty, R. Mackenzie, N. Gill, and A. A. Ashkar Cutting Edge: FimH Adhesin of Type 1 Fimbriae Is a Novel TLR4 Ligand J. Immunol., November 15, 2008; 181(10): 6702 - 6706. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. J. Kaiser, J. W. Upton, and E. S. Mocarski Receptor-Interacting Protein Homotypic Interaction Motif-Dependent Control of NF-{kappa}B Activation via the DNA-Dependent Activator of IFN Regulatory Factors J. Immunol., November 1, 2008; 181(9): 6427 - 6434. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. E. Randall and S. Goodbourn Interferons and viruses: an interplay between induction, signalling, antiviral responses and virus countermeasures J. Gen. Virol., January 1, 2008; 89(1): 1 - 47. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. B. Rasmussen, L. N. Sorensen, L. Malmgaard, N. Ank, J. D. Baines, Z. J. Chen, and S. R. Paludan Type I Interferon Production during Herpes Simplex Virus Infection Is Controlled by Cell-Type-Specific Viral Recognition through Toll-Like Receptor 9, the Mitochondrial Antiviral Signaling Protein Pathway, and Novel Recognition Systems J. Virol., December 15, 2007; 81(24): 13315 - 13324. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Suzuki, T. Imaizumi, K. Tsugawa, E. Ito, and H. Tanaka Expression of retinoic acid-inducible gene-I in lupus nephritis Nephrol. Dial. Transplant., August 1, 2007; 22(8): 2407 - 2409. [Full Text] [PDF]
|
|
|
|
|
|
J. B. Prescott, P. R. Hall, V. S. Bondu-Hawkins, C. Ye, and B. Hjelle Early Innate Immune Responses to Sin Nombre Hantavirus Occur Independently of IFN Regulatory Factor 3, Characterized Pattern Recognition Receptors, and Viral Entry J. Immunol., August 1, 2007; 179(3): 1796 - 1802. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
