| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520;
L2 Diagnostics, New Haven, CT 06511;
Department of Molecular Biophysics and Biochemistry, Bass Center for Structural Biology, Yale University, New Haven, CT 06520; and
Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520
The immune response against viral infection relies on the early production of cytokines that induce an antiviral state and trigger the activation of immune cells. This response is initiated by the recognition of virus-associated molecular patterns such as dsRNA, a viral replication intermediate recognized by TLR3 and certain RNA helicases. Infection with West Nile virus (WNV) can lead to lethal encephalitis in susceptible individuals and constitutes an emerging health threat. In this study, we report that WNV envelope protein (WNV-E) specifically blocks the production of antiviral and proinflammatory cytokines induced by dsRNA in murine macrophages. This immunosuppressive effect was not dependent on TLR3 or its adaptor molecule Trif. Instead, our experiments show that WNV-E acts at the level of receptor-interacting protein 1. Our results also indicate that WNV-E requires a certain glycosylation pattern, specifically that of dipteran cells, to inhibit dsRNA-induced cytokine production. In conclusion, these data show that the major structural protein of WNV impairs the innate immune response and suggest that WNV exploits differential vector/host E glycosylation profiles to evade antiviral mechanisms.
1 This work was supported by awards from the National Institutes of Health, including AI-50031 and AI-055749. T.T. was supported by an National Institutes of Health/National Institute on Aging "Pathway to Independence" award (1 K99 AG029726-01).
2 Address correspondence and reprint requests to Dr. Erol Fikrig, Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, P.O. Box 208022, New Haven, CT 06520. E-mail address: erol.fikrig{at}yale.edu
3 Abbreviations used in this paper: PRR, pattern-recognition receptors; RIG-I, retinoic acid-inducible gene I; MDA5, melanoma differentiation-associated gene 5; RIP1, receptor-interacting protein 1; TBK1, TANK-binding kinase 1; IRF, IFN regulatory factors; WNV, West Nile virus; WNV-E, West Nile virus envelope protein; PAMP, pathogen-associated molecular pattern; EGCG, (-)-epigallochatechin gallate.
This article has been cited by other articles:
|
|
 |
|
  R. S. Shabman, K. M. Rogers, and M. T. Heise Ross River Virus Envelope Glycans Contribute to Type I Interferon Production in Myeloid Dendritic Cells J. Virol., December 15, 2008; 82(24): 12374 - 12383. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Daffis, M. A. Samuel, M. S. Suthar, M. Gale Jr., and M. S. Diamond Toll-Like Receptor 3 Has a Protective Role against West Nile Virus Infection J. Virol., November 1, 2008; 82(21): 10349 - 10358. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K.-F. Kong, K. Delroux, X. Wang, F. Qian, A. Arjona, S. E. Malawista, E. Fikrig, and R. R. Montgomery Dysregulation of TLR3 Impairs the Innate Immune Response to West Nile Virus in the Elderly J. Virol., August 1, 2008; 82(15): 7613 - 7623. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
