Analysis of the differential host cell nuclear proteome induced by attenuated and virulent hemorrhagic arenavirus infection

Gavin C. Bowick, Heidi Spratt, Alison E. Hogg, Janice Endsley, John E. Wiktorowicz, Alexander Kurosky, Bruce A. Luxon, David G. Gorenstein, Norbert K. Herzog

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

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-κB 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.

Original languageEnglish (US)
Pages (from-to)687-700
Number of pages14
JournalJournal of Virology
Volume83
Issue number2
DOIs
StatePublished - Jan 2009

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Arenaviridae Infections
Arenavirus
Proteome
proteome
Viruses
Infection
Major Histocompatibility Complex
infection
viruses
New World Arenaviruses
Transcription Factors
Lassa virus
National Institute of Allergy and Infectious Diseases (U.S.)
major histocompatibility complex
cells
lethal genes
Arenaviridae
Electrophoresis, Gel, Two-Dimensional
Electrophoretic Mobility Shift Assay
Virus Diseases

ASJC Scopus subject areas

  • Immunology
  • Virology

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Analysis of the differential host cell nuclear proteome induced by attenuated and virulent hemorrhagic arenavirus infection. / Bowick, Gavin C.; Spratt, Heidi; Hogg, Alison E.; Endsley, Janice; Wiktorowicz, John E.; Kurosky, Alexander; Luxon, Bruce A.; Gorenstein, David G.; Herzog, Norbert K.

In: Journal of Virology, Vol. 83, No. 2, 01.2009, p. 687-700.

Research output: Contribution to journalArticle

Bowick, Gavin C. ; Spratt, Heidi ; Hogg, Alison E. ; Endsley, Janice ; Wiktorowicz, John E. ; Kurosky, Alexander ; Luxon, Bruce A. ; Gorenstein, David G. ; Herzog, Norbert K. / Analysis of the differential host cell nuclear proteome induced by attenuated and virulent hemorrhagic arenavirus infection. In: Journal of Virology. 2009 ; Vol. 83, No. 2. pp. 687-700.
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