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Journal of Virology, January 2009, p. 687-700, Vol. 83, No. 2
0022-538X/09/$08.00+0 doi:10.1128/JVI.01281-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
Analysis of the Differential Host Cell Nuclear Proteome Induced by Attenuated and Virulent Hemorrhagic Arenavirus Infection
,
Gavin C. Bowick,1,4,5
Heidi M. Spratt,6,7
Alison E. Hogg,3
Janice J. Endsley,3
John E. Wiktorowicz,2,7
Alexander Kurosky,2,7
Bruce A. Luxon,2,4,6
David G. Gorenstein,2,4,7 and
Norbert K. Herzog1,3,4,5*
Department of Pathology,1 Department of Biochemistry and Molecular Biology,2 Department of Microbiology and Immunology,3 Center for Biodefense and Emerging Infectious Diseases,4 Institute for Human Infections and Immunity,5 Bioinformatics Program,6 NHLBI Proteomics Center, University of Texas Medical Branch, Galveston, Texas7
Received 19 June 2008/ Accepted 24 October 2008
Arenaviruses are important emerging pathogens and include a number of hemorrhagic fever viruses classified as NIAID category A priority pathogens and CDC potential biothreat agents. Infection of guinea pigs with the New World arenavirus Pichindé virus (PICV) has been used as a biosafety level 2 model for the Lassa virus. Despite continuing research, little is known about the molecular basis of pathogenesis, and this has hindered the design of novel antiviral therapeutics. Modulation of the host response is a potential strategy for the treatment of infectious diseases. We have previously investigated the global host response to attenuated and lethal arenavirus infections by using high-throughput immunoblotting and kinomics approaches. In this report, we describe the differential nuclear proteomes of a murine cell line induced by mock infection and infection with attenuated and lethal variants of PICV, investigated by using two-dimensional gel electrophoresis. Spot identification using tandem mass spectrometry revealed the involvement of a number of proteins that regulate inflammation via potential modulation of NF-
B activity and of several heterogeneous nuclear ribonuclear proteins. Pathway analysis revealed a potential role for transcription factor XBP-1, a transcription factor involved in major histocompatibility complex II (MHC-II) expression; differential DNA-binding activity was revealed by electrophoretic mobility shift assay, and differences in surface MHC-II expression were seen following PICV infection. These data are consistent with the results of several previous studies and highlight potential differences between transcriptional and translational regulation. This study provides a number of differentially expressed targets for further research and suggests that key events in pathogenesis may be established early in infection.
* Corresponding author. Mailing address: 301 University Boulevard, Galveston, TX 77555-0609. Phone: (409) 772-3938. Fax: (409) 772-2400. E-mail: nherzog{at}utmb.edu
Published ahead of print on 12 November 2008.
Supplemental material for this article may be found at http://jvi.asm.org/.
Journal of Virology, January 2009, p. 687-700, Vol. 83, No. 2
0022-538X/09/$08.00+0 doi:10.1128/JVI.01281-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
Copyright © 2009 by the American Society for Microbiology. For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»