HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 276, Issue 23, 19889-19896, June 8, 2001

This Article Full Text Full Text (PDF) All Versions of this Article: 276/23/19889    most recent M100499200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by LaMonica, R. Articles by Mackow, E. R. Search for Related Content PubMed PubMed Citation Articles by LaMonica, R. Articles by Mackow, E. R. Social Bookmarking                      What's this?

VP4 Differentially Regulates TRAF2 Signaling, Disengaging JNK Activation while Directing NF-B to Effect Rotavirus-specific Cellular Responses^*

Rachel LaMonica^§¶, Salih S. Kocer^§¶, Jennet Nazarova, William Dowling^§**, Erika Geimonen^§¶, Robert D. Shaw^¶, and Erich R. Mackow^§¶

From the  Department of Medicine, ^§ Department of Molecular Genetics and Microbiology, and  Molecular Cell Biology Program, State University of New York, Stony Brook, New York 11794, ^¶ Northport Veterans Affairs Medical Center, Northport, New York 11768, and ^** Department of Retrovirology, Walter Reed Army Institute of Research, Rockville, Maryland 20850

Rotaviruses rapidly activate NF-B and induce the secretion of selected chemokines after infection. The ability of rotavirus particles lacking genomic RNA to activate NF-B suggested that rotavirus proteins direct cell signaling responses. We identified conserved TNFR-associated factor (TRAF) binding motifs within the rotavirus capsid protein VP4 and its N-terminal VP8* cleavage product. TRAFs (-1, -2, and -3) are bound by the rhesus rotavirus VP8* protein through three discrete TRAF binding domains. Expression of VP4 or VP8* from rhesus or human rotaviruses induced a 5-7-fold increase in NF-B activity and synergistically enhanced TRAF2-mediated NF-B activation. Mutagenesis of VP8* TRAF binding motifs abolished VP8* binding to TRAFs and the ability of the protein to activate NF-B. Expression of pathway-specific dominant negative (DN) inhibitors DN-TRAF2 or DN-NF-B-inducing kinase also abolished VP8*-, VP4-, or rotavirus-mediated NF-B activation. These findings demonstrate that rotavirus primarily activates NF-B through a TRAF2-NF-B-inducing kinase signaling pathway and that VP4 and VP8* proteins direct pathway activation through interactions with cellular TRAFs. In contrast, transcriptional responses from AP-1 reporters were inhibited 5-fold by VP8* and were not activated by rotavirus infection, suggesting the differential regulation of TRAF2 signaling responses by VP8*. VP8* blocked JNK activation directed by TRAF2 or TRAF5 but had no effect on JNK activation directed by TRAF6 or MEKK1. This establishes that fully cytoplasmic rotaviruses selectively engage signaling pathways, which regulate cellular transcriptional responses. These findings also demonstrate that TRAF2 interactions can disengage JNK signaling from NF-B activation and thereby provide a new means for TRAF2 interactions to determine pathway-specific responses.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				S. Libersou, X. Siebert, M. Ouldali, L. F. Estrozi, J. Navaza, A. Charpilienne, P. Garnier, D. Poncet, and J. Lepault Geometric Mismatches within the Concentric Layers of Rotavirus Particles: a Potential Regulatory Switch of Viral Particle Transcription Activity J. Virol., March 15, 2008; 82(6): 2844 - 2852. [Abstract] [Full Text] [PDF]

				G. Holloway and B. S. Coulson Rotavirus Activates JNK and p38 Signaling Pathways in Intestinal Cells, Leading to AP-1-Driven Transcriptional Responses and Enhanced Virus Replication J. Virol., November 1, 2006; 80(21): 10624 - 10633. [Abstract] [Full Text] [PDF]

				A. Sen, D. Agresti, and E. R. Mackow Hyperphosphorylation of the Rotavirus NSP5 Protein Is Independent of Serine 67 or NSP2, and the Intrinsic Insolubility of NSP5 Is Regulated by Cellular Phosphatases J. Virol., February 15, 2006; 80(4): 1807 - 1816. [Abstract] [Full Text] [PDF]

				N. Monnier, K. Higo-Moriguchi, Z.-Y. J. Sun, B. V. V. Prasad, K. Taniguchi, and P. R. Dormitzer High-Resolution Molecular and Antigen Structure of the VP8* Core of a Sialic Acid-Independent Human Rotavirus Strain J. Virol., February 1, 2006; 80(3): 1513 - 1523. [Abstract] [Full Text] [PDF]

				G. Maloney, M. Schroder, and A. G. Bowie Vaccinia Virus Protein A52R Activates p38 Mitogen-activated Protein Kinase and Potentiates Lipopolysaccharide-induced Interleukin-10 J. Biol. Chem., September 2, 2005; 280(35): 30838 - 30844. [Abstract] [Full Text] [PDF]

				S. P. Fessler, Y. R. Chin, and M. S. Horwitz Inhibition of Tumor Necrosis Factor (TNF) Signal Transduction by the Adenovirus Group C RID Complex Involves Downregulation of Surface Levels of TNF Receptor 1 J. Virol., December 1, 2004; 78(23): 13113 - 13121. [Abstract] [Full Text] [PDF]

				J. W. A. Rossen, J. Bouma, R. H. C. Raatgeep, H. A. Buller, and A. W. C. Einerhand Inhibition of Cyclooxygenase Activity Reduces Rotavirus Infection at a Postbinding Step J. Virol., September 15, 2004; 78(18): 9721 - 9730. [Abstract] [Full Text] [PDF]

				M. T. Harte, I. R. Haga, G. Maloney, P. Gray, P. C. Reading, N. W. Bartlett, G. L. Smith, A. Bowie, and L. A.J. O'Neill The Poxvirus Protein A52R Targets Toll-like Receptor Signaling Complexes to Suppress Host Defense J. Exp. Med., February 3, 2003; 197(3): 343 - 351. [Abstract] [Full Text] [PDF]

				S. Ludwig, X. Wang, C. Ehrhardt, H. Zheng, N. Donelan, O. Planz, S. Pleschka, A. Garcia-Sastre, G. Heins, and T. Wolff The Influenza A Virus NS1 Protein Inhibits Activation of Jun N-Terminal Kinase and AP-1 Transcription Factors J. Virol., November 19, 2002; 76(21): 11166 - 11171. [Abstract] [Full Text] [PDF]

				M. Ciarlet, S. E. Crawford, E. Cheng, S. E. Blutt, D. A. Rice, J. M. Bergelson, and M. K. Estes VLA-2 ({alpha}2{beta}1) Integrin Promotes Rotavirus Entry into Cells but Is Not Necessary for Rotavirus Attachment J. Virol., February 1, 2002; 76(3): 1109 - 1123. [Abstract] [Full Text] [PDF]

				M. Ciarlet, S. E. Crawford, and M. K. Estes Differential Infection of Polarized Epithelial Cell Lines by Sialic Acid-Dependent and Sialic Acid-Independent Rotavirus Strains J. Virol., December 1, 2001; 75(23): 11834 - 11850. [Abstract] [Full Text]