Identification of differentially activated cell-signaling networks associated with Pichinde virus pathogenesis by using systems kinomics

Gavin C. Bowick, Susan M. Fennewald, Erin P. Scott, LiHong Zhang, Barry L. Elsom, Judith Aronson, Heidi Spratt, Bruce A. Luxon, David G. Gorenstein, Norbert K. Herzog

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

Phosphorylation plays a key role in regulating many signaling pathways. Although studies investigating the phosphorylated forms of signaling pathways are now commonplace, global analysis of protein phosphorylation and kinase activity has lagged behind genomics and proteomics. We have used a kinomics approach to study the effect of virus infection on host cell signaling in infected guinea pigs. Delineating the host responses which lead to clearance of a pathogen requires the use of a matched, comparative model system. We have used two passage variants of the arenavirus Pichinde, used as a biosafety level 2 model of Lassa fever virus as it produces similar pathologies in guinea pigs and humans, to compare the host cell responses between infections which lead to either a mild, self-limiting infection or lethal disease. Using this model, we can begin to understand the differences in signaling events which give rise to these markedly different outcomes. By contextualizing these data using pathway analysis, we have identified key differences in cellular signaling matrices. By comparing these differentially involved networks, we have identified a number of key signaling "nodes" which show differential phosphorylations between mild and lethal infections. We believe that these nodes provide potential targets for the development of antiviral therapies by acting at the level of the host response rather than by directly targeting viral proteins.

Original languageEnglish (US)
Pages (from-to)1923-1933
Number of pages11
JournalJournal of Virology
Volume81
Issue number4
DOIs
StatePublished - Feb 2007

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Pichinde virus
pathogenesis
Phosphorylation
Guinea Pigs
Lassa Fever
Lassa virus
Infection
Arenavirus
infection
guinea pigs
phosphorylation
Viral Proteins
Virus Diseases
cells
Genomics
Proteomics
viruses
cell communication
Protein Kinases
biosafety

ASJC Scopus subject areas

  • Immunology

Cite this

Identification of differentially activated cell-signaling networks associated with Pichinde virus pathogenesis by using systems kinomics. / Bowick, Gavin C.; Fennewald, Susan M.; Scott, Erin P.; Zhang, LiHong; Elsom, Barry L.; Aronson, Judith; Spratt, Heidi; Luxon, Bruce A.; Gorenstein, David G.; Herzog, Norbert K.

In: Journal of Virology, Vol. 81, No. 4, 02.2007, p. 1923-1933.

Research output: Contribution to journalArticle

Bowick, Gavin C. ; Fennewald, Susan M. ; Scott, Erin P. ; Zhang, LiHong ; Elsom, Barry L. ; Aronson, Judith ; Spratt, Heidi ; Luxon, Bruce A. ; Gorenstein, David G. ; Herzog, Norbert K. / Identification of differentially activated cell-signaling networks associated with Pichinde virus pathogenesis by using systems kinomics. In: Journal of Virology. 2007 ; Vol. 81, No. 4. pp. 1923-1933.
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